99mTc Sestamibi Thyroid Scan in Amiodarone-Induced Thyrotoxicosis Type I.

PubMed

Patel, Niraj R; Tamara, Luis A; Lee, Ho

2016-07-01

Amiodarone-induced thyrotoxicosis (AIT) type I describes inducement of clinical hyperthyroidism by excessive thyroidal iodine in the setting of latent Graves disease, and therapy differs from that used for AIT type II. A 65-year-old man previously on amiodarone for atrial fibrillation developed clinical hyperthyroidism. Diagnosis of AIT was made, but the type was not clear. Tc sestamibi thyroid scan showed diffusely increased uptake and retention in an enlarged thyroid gland, a pattern consistent with AIT type I. Methimazole was initiated and controlled the thyrotoxicosis. I iodide thyroid scan and uptake study performed later was consistent with Graves disease.

High failure rates after (131)I therapy in Graves hyperthyroidism patients with large thyroid volumes, high iodine uptake, and high iodine turnover.

PubMed

de Jong, Jeroen A F; Verkooijen, Helena M; Valk, Gerlof D; Zelissen, Pierre M J; de Keizer, Bart

2013-06-01

The objective of this study was to identify patient characteristics positively and independently associated with I-iodide treatment failure in a large cohort of patients with Graves hyperthyroidism treated with either a calculated "standard" activity of 3.7 MBq/mL (0.1 mCi) or 7.4 MBq/mL (0.2 mCi) of thyroid volume. Data on 385 consecutive patients were prospectively collected. Clinical treatment outcome up to 1 year in relation to thyroid volume, 5- and 24-hour I uptake, 5/24-hour I uptake ratio, and the administered activity of radioiodine were analyzed. Overall treatment results were hypothyroidism in 46%, euthyroidism in 29%, and recurrent hyperthyroidism in 26% of patients. Thyroid volume (P = 0.000), 5/24-hour uptake ratio (P = 0.000), and 5- and 24-hour uptake alone (respectively, P = 0.000 and P = 0.002) were significantly associated with therapy outcome. Patients with a combination of a thyroid volume greater than 50 mL and a 5/24-hour uptake ratio 0.8 or greater showed treatment failure in 70% and 42% (respectively, 3.7 MBq/mL, n = 20; and 7.4 MBq/mL, n = 41).Thyroid volume and 5/24-hour uptake ratio were positively and independently associated with recurrent hyperthyroidism (respectively, odds ratio [OR], 5.3; 95% confidence interval [CI], 2.39-11.76; and OR, 2.97; 95% CI, 1.59-5.59). Higher activities of 7.4 MBq/mL I were associated with a lower risk of treatment failure (OR, 0.34; 95% CI, 0.18-0.62). Large thyroid volumes and high 5/24-hour uptake ratios are positively and independently associated with recurrent hyperthyroidism following I therapy in Graves hyperthyroidism. Higher success rates can be achieved when account is taken of these poor prognostic factors. In consequence, these patients should be treated with activities greater than 7.4 MBq/mL.

18F-FDG PET/CT Can Predict Development of Thyroiditis due to Immunotherapy for Lung Cancer.

PubMed

Eshghi, Naghmehossadat; Garland, Linda; Nia, Emily Saghar; Betancourt, Robert; Krupinski, Elizabeth; Kuo, Phillip H

2018-03-29

Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased 18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if 18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with 18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver and spleen. Patients obtained monthly thyroid testing. PET/CT parameters were analyzed by unpaired t-test for differences between two groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab received was also tested. Results: Six of eighteen patients developed hypothyroidism. T-test comparing the two groups (patients who developed hypothyroidism and those who did not) demonstrated significant differences in SUVmean ( P = 0.04), SUV max ( P = 0.04) and TLG ( P = 0.02) of the thyroid gland. Two of four patients who developed thyroiditis and had increased 18 F-FDG uptake in the thyroid gland, had normal TSH at time of follow-up 18 F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) compared to patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver or spleen. Conclusion: 18 F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno, A.J.; Brown, J.M.; Salinas, J.A.

1984-03-01

Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

Iodine concentration calculated by dual-energy computed tomography (DECT) as a functional parameter to evaluate thyroid metabolism in patients with hyperthyroidism.

PubMed

Binh, Duong Duc; Nakajima, Takahito; Otake, Hidenori; Higuchi, Tetsuya; Tsushima, Yoshito

2017-07-19

Thyroid function in patients with Grave's disease is usually evaluated by thyroid scintigraphy with radioactive iodine. Recently, dual-energy computed tomography (DECT) with two different energy X-rays can calculate iodine concentrations and can be applied for iodine measurements in thyroid glands. This study aimed to assess the potential use of DECT for the functional assessment of the thyroid gland. Thirteen patients with Grave's disease treated at our hospital from May to September 2015 were included in this retrospective study. Before treatments, all subjects had undergone both iodine scintigraphy [three and 24 h after oral administration of 123 I (20 μCi)] and non-enhanced DECT. The region of interests (ROIs) were placed in both lobes of the thyroid glands, and CT values (HU: Hounsfield unit) and iodine concentrations (mg/mL) calculated from DECT images were measured. The correlation between CT values and iodine concentrations from DECT in the thyroid gland was evaluated and then the iodine concentrations were compared with radioactive iodine uptake ratios by thyroid scintigraphy. Mean (±SD) 123 I uptake increased from 46.3 (±22.2) % (range, 11.1-80.1) at 3 h, to 66.5 (±15.2) % (range, 40.0-86.1) at 24 h (p < 0.01). CT values ranged from 34.5 to 98.7 HU [mean: 67.8 (±18.6)], while the iodine concentrations calculated with DECT ranged from 0.0 to 1.3 mg/mL [mean: 0.5 (±0.4)]. A moderate positive correlation between CT values and the calculated iodine concentrations in the thyroid gland was seen (R = 0.429, p < 0.05). A significant negative correlation between 123 I uptake at 3 h and iodine concentration by DECT were seen (R = -0.680, p < 0.05), although no correlation was observed between 123 I uptake at 3 h and CT values (p = 0.087). No correlation was observed between 123 I uptake at 24 h and CT values (p = 0.153) or that between 123 I uptake at 24 h and iodine concentration by DECT (p = 0.073). The negative correlation of 123 I uptake at 3 h with iodine concentration evaluated by DECT was better than that observed with simple CT value. DECT may have a potential role in the evaluation of iodine turnover in hyperthyroid patients.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules

PubMed Central

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-01-01

[99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained. PMID:29212258

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules.

PubMed

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-11-07

[ 99m Tc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

Disguised Thyroid Disorders

PubMed Central

Tsao, John M.; Catz, Boris

1965-01-01

In six cases of hyperthyroidism and two of chronic thyroiditis herein described, the initial features of the diseases were misinterpreted as attributable to other kinds of illness such as myocardial infarction, gastrointestinal malignant disease, malabsorption syndrome, psychosis, simple exophthalmos and endemic goiter. The characteristic signs and symptoms of hyperthyroidism (in six patients) and chronic thyroiditis (in two patients) were present at the outset but were not identified. Intensive questioning and alertness were required to elicit these characteristics. The symptoms improved or disappeared after the true disease was controlled. In the studies of these cases, the usefulness of a number of laboratory tests was illustrated—thyroid suppression studies, 4 to 6-hour and 24-hour radioactive iodine uptake, T3 uptake by the red cells and determinations of 24-hour urine creatine, antithyroglobulin antibody titer and long-acting thyroid stimulating hormone. The manifestations of thyroid diseases are many and varied. The term “masked hyperthyroidism” may in part be a reflection of the “masked physician” unless he uses his clinical detective abilities. PMID:14347981

Thyroiditis

MedlinePlus

... 12-18 months, 20% possibility of permanent hypothyroidism. Post partum thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism. Thyroid function tests, thyroid antibody tests, radioactive iodine uptake (contraindicated if ...

Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

PubMed Central

Kim, Hyun Joo; Bang, Ji-In; Kim, Ji-Young; Moon, Jae Hoon; So, Young

2017-01-01

Objective Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. Materials and Methods A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of 99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. Results GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). Conclusion A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients. PMID:28458607

PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.

PubMed

Nakhjavani, Manouchehr; Abdollahi, Soraya; Farzanefar, Saeed; Abousaidi, Mohammadtagi; Esteghamati, Alireza; Naseri, Maryam; Eftekhari, Mohamad; Abbasi, Mehrshad

2017-04-02

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement. Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic. Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3). TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal. ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Flavonoids, Thyroid Iodide Uptake and Thyroid Cancer—A Review

PubMed Central

Gonçalves, Carlos F. L.; de Freitas, Mariana L.; Ferreira, Andrea C. F.

2017-01-01

Thyroid cancer is the most common malignant tumor of the endocrine system and the incidence has been increasing in recent years. In a great part of the differentiated carcinomas, thyrocytes are capable of uptaking iodide. In these cases, the main therapeutic approach includes thyroidectomy followed by ablative therapy with radioiodine. However, in part of the patients, the capacity to concentrate iodide is lost due to down-regulation of the sodium-iodide symporter (NIS), the protein responsible for transporting iodide into the thyrocytes. Thus, therapy with radioiodide becomes ineffective, limiting therapeutic options and reducing the life expectancy of the patient. Excessive ingestion of some flavonoids has been associated with thyroid dysfunction and goiter. Nevertheless, studies have shown that some flavonoids can be beneficial for thyroid cancer, by reducing cell proliferation and increasing cell death, besides increasing NIS mRNA levels and iodide uptake. Recent data show that the flavonoids apingenin and rutin are capable of increasing NIS function and expression in vivo. Herein we review literature data regarding the effect of flavonoids on thyroid cancer, besides the effect of these compounds on the expression and function of the sodium-iodide symporter. We will also discuss the possibility of using flavonoids as adjuvants for therapy of thyroid cancer. PMID:28604619

[Thyroiditis].

PubMed

Buffet, Camille; Groussin, Lionel

2013-02-01

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagareda, C.S.; Kaplan, H.S.

1959-04-01

Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism.

PubMed

van Hoek, Ingrid M; Vandermeulen, Eva; Peremans, Kathelijne; Daminet, Sylvie

2010-02-01

This study investigated the recombinant human thyrotropin (rhTSH) stimulation test in healthy cats (group 1), cats with non-thyroidal illness (group 2) and cats with low serum total T(4) (TT(4)) and azotaemia after (131)I treatment (group 3). Serum TT(4) responses and thyroidal pertechnetate uptake after administration of 25 microg rhTSH IV were assessed. Baseline serum TT(4) was significantly lower in group 3 compared with group 1, but not between other group pairs. Serum TT(4) increased significantly in groups 1 and 2 but not in group 3 after rhTSH administration. Post-rhTSH serum TT(4) concentrations differed significantly between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. Thyroid/salivary gland uptake ratio (T/S uptake ratio) differed only significantly between groups 1 and 3. Stimulation with rhTSH is valuable to differentiate euthyroidism from iatrogenic hypothyroidism in cats. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

PubMed

Diaz Espineira, M M; Mol, J A; Peeters, M E; Pollak, Y W E A; Iversen, L; van Dijk, J E; Rijnberk, A; Kooistra, H S

2007-01-01

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

Thyroid scintigraphy findings in 2096 cats with hyperthyroidism.

PubMed

Peterson, Mark E; Broome, Michael R

2015-01-01

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism, but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive cats with hyperthyroidism that were referred over a 3.5-year period. Of these cats, 2068 (98.7%) had a high thyroid-to-salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid-to-background ratio (>6.1). When the patterns of the cats' thyroid disease were recorded, 665 (31.7%) had unilateral disease, 1060 (50.6%) had bilateral-asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral-symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (≥3 areas of increased radionuclide uptake). The number of areas of (99m) TcO(-) 4 uptake in the 2096 cats ranged from 1 to 6 (median, 2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115 (5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma are relatively uncommon in hyperthyroid cats, with a respective prevalence of ∼4% and ∼2% in this study. © 2014 American College of Veterinary Radiology.

Thyroid uptake of (/sup 99m/Tc) pertechnetate during in vivo RBC labeling: incidental diagnosis of hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, K.A.; Ponto, J.A.

1981-09-01

Increased thyroid activity was incidentally observed during an in vivo labeled Tc-99m blood pool scan and subsequent evaluation resulted in a diagnosis of hypothyroidism. Alternate explanations of abnormal thyroid uptake on in vivo labeled blood pool scans were considered and are discussed briefly.

Thyroid scan

MedlinePlus

... thyroid; Radioactive iodine uptake and scan test - thyroid; Nuclear scan - thyroid ... the test. Ask your provider or the radiology/nuclear medicine team performing the scan about taking precautions.

Marked suppression of thyroid function in rats with gram-negative septicemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kan, M.K.; Garcia, J.F.; McRae, J.

1976-02-01

Gram-negative septicemia was induced in rats by two daily injections of fecal mixture into the thigh, after which the thyroid function was markedly suppressed for 2 days. Iodine metabolism was studied by organ radioassay and by imaging with a multiwire proportional chamber (MWPC) at various time intervals after intravenous injection of $sup 125$I. Plasma T$sub 3$, T$sub 4$, and TSH, measured by radioimmunoassays, were suppressed, as were the T$sub 3$-resin uptakes. Fractional blood supply to the thyroid glands of the infected rats, studied by the $sup 81$Rb uptake method, was also found to be markedly reduced. Sections of the thyroidmore » glands showed little structural change during the period of marked thyroid suppression. There was no biochemical evidence of renal failure in the septicemic rats. (auth)« less

KT5823 Differentially Modulates Sodium Iodide Symporter Expression, Activity, and Glycosylation between Thyroid and Breast Cancer Cells

PubMed Central

Beyer, Sasha; Lakshmanan, Aparna; Liu, Yu-Yu; Zhang, Xiaoli; Wapnir, Irene; Smolenski, Albert

2011-01-01

Na+/I− symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels. PMID:21209020

[Painless thyroiditis].

PubMed

Okamura, Ken; Fujikawa, Megumi; Bandai, Sachiko

2006-12-01

Painless thyroiditis is characterized by painless low-uptake thyrotoxicosis (thyrotoxicosis without hyperthyroidism). Destructive damage of the thyroid has been thought to be the mechanism for self-limited thyrotoxicosis. However, hydrolysis of thyroglobulin must be responsible for the release of excessive thyroid hormone. Low-uptake of iodine and excessive release of thyroid hormone suggest the uncoupling of hormone synthesis and hormone secretion in the thyroid gland. Suppressed serum TSH level, various cytokines or growth factors including TGFbeta1, and thyroglobulin itself may be responsible for the suppressed hormone synthesis. The mechanism for persistent hormone release despite suppressed hormone synthesis should be clarified. Quantitative TSH binding inhibitor immunoglobulin assay is helpful for the differential diagnosis of painless thyroiditis and Graves' hyperthyroidism.

Modulation of Sodium Iodide Symporter in Thyroid Cancer

PubMed Central

Lakshmanan, Aparna; Scarberry, Daniel

2015-01-01

Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future. PMID:25234361

SPECT/CT demonstrating 131I retention in Warthin tumor on thyroid cancer survey scan.

PubMed

Zhang, Yuyang; Minoshima, Satoshi

2013-09-01

A 48-year-old male patient of papillary thyroid cancer, status post-thyroidectomy and node dissection, was referred to (131)I scan prior to radioiodine treatment. The images showed 1 additional focus of (131)I uptake in the right upper neck outside of the thyroid bed. SPECT/CT demonstrated 2 separate foci of radioiodine uptake in the right parotid gland, instead of neck lymph nodes. Diagnostic CT showed 2 corresponding soft tissue nodules in the right parotid gland which were confirmed latter by fine-needle aspiration to be Warthin tumors. This case illustrates a pivotal role of SPECT/CT in differential diagnosis of abnormal neck uptake on (131)I thyroid cancer scan.

The significance of folic acid, tissue iron stores, and tissue viability in determining iron uptake from serum by thyroid tissue slices

PubMed Central

Buchanan, W. M.

1971-01-01

This paper describes an attempt to measure in vitro iron uptake from serum by human thyroid slices and to relate the uptake to tissue iron stores, folic acid status, and tissue viability. It is an extension of work previously reported (Buchanan, 1969). Thyroids were obtained from patients undergoing partial thyroidectomy for colloid goitre and serum from clinically normal healthy adults. The haemoglobin, serum iron, and folic acid levels of both thyroid and serum donors were measured and thyroids examined histologically for the presence of stainable iron. Viable and non-viable tissue slices were incubated in sera treated with radioactive iron so as to produce high and normal levels of transferrin saturation. Iron was taken up both from sera with normal and high transferrin saturation but the amount was, in almost all cases, greater from the more highly saturated. The uptake by non-viable tissue was appreciable but did not vary to any great extent from one serum to the next, and was attributed to simple diffusion of ionic iron into the tissue. There was, however, marked variation in uptake from different sera by viable tissue. It was concluded therefore that viability is a factor affecting the uptake. As the variation in uptake by viable tissue incubated in a single serum was significantly less than tissue incubated in a number of different sera it was further concluded that there was also a factor in the serum itself affecting iron uptake. The nature of the factor was not elucidated but neither folic acid nor levels of iron stores appeared to influence uptake because no correlation was found between iron uptake and iron stores or folic acid. Images PMID:5556118

18F-FDG PET/CT imaging of atypical subacute thyroiditis in thyrotoxicosis: A case report.

PubMed

Yoshida, Katsuya; Yokoh, Hidetaka; Toriihara, Akira; Fujii, Hayahiko; Harata, Naoki; Isogai, Jun; Tateishi, Ukihide

2017-07-01

In addition to its established role in oncologic imaging, F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) is useful for the assessment of inflammatory activity. However, subacute thyroiditis (SAT) in thyrotoxicosis is rarely detected during these scans. A 66-year-old man with SAT in thyrotoxicosis demonstrated symptoms of transient fatigue, headache, and fever, without typical neck pain. Using F-FDG PET/CT, we found increased F-FDG uptake in the thyroid gland, predominantly in the right side due to SAT. We also observed a coexisting decrease in F-FDG uptake in the liver and increased F-FDG uptake in skeletal muscle due to thyrotoxicosis. Using F-FDG PET/CT, the combined observations of increased F-FDG uptake in the thyroid and skeletal muscle, and decreased F-FDG uptake in the liver, even when the typical symptom of neck pain is subtle or absent, may be helpful for the differential diagnosis of SAT in thyrotoxicosis.

Thyroid and parathyroid imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandler, M.P.; Patton, J.A.; Partain, C.L.

1986-01-01

This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies.more » X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.« less

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

PubMed

Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M

2013-09-01

Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I− uptake

PubMed Central

Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan P.; Koba, Wade; Fine, Eugene; Carrasco, Nancy; Abbott, Geoffrey W.

2012-01-01

The KCNQ1 α subunit and the KCNE2 β subunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (−)-[3R,4S]-chromanol 293B (C293B) significantly impaired thyroid cell I− uptake, which is mediated by the Na+/I− symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028±0.004 min−1; 10 mg/kg C293B, 0.009±0.006 min−1) and in vitro (EC50: 99±10 μM C293B). Na+-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I− in the thyroid (distinguished using ClO4−, a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I− organification. However, Kcne2 deletion doubled the rate of free I− efflux from the thyroid following ClO4− injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I− uptake, the most likely explanation being that it is prerequisite for adequate NIS activity.—Purtell, K., Paroder-Belenitsky, M., Reyna-Neyra, A., Nicola, J. P., Koba, W., Fine, E., Carrasco, N., Abbott, G. W. The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I− uptake. PMID:22549510

The frequency and spectrum of thymus 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake patterns in hyperthyroidism patients.

PubMed

Chen, Yen-Kung; Yeh, Chia-Lu; Chen, Yen-Ling; Wang, Su-Chen; Cheng, Ru-Hwa; Kao, Pan-Fu

2011-10-01

Thymic hyperplasia is associated with hyperthyroidism. Increased thymus 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in hyperthyroidism patients has been reported. The aim of this study was to analyze the FDG positron emission tomography (PET) thymus uptake spectrum in patients with active hyperthyroidism with correlation with serum hormones. The prospective study included FDG PET scans from 65 hyperthyroidism patients and 30 subjects with euthyroid status as control group. The intensity of FDG uptake in thyroid and thymus regions was graded subjectively on a five-point scale and semi-quantitatively by measuring standard uptake value (SUV). Correlation coefficient between thymus SUV and serum thyroxine, triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPO Ab), thyrotropin receptor autoantibody (TR Ab), and thymulin were analyzed. Among 65 hyperthyroidism patients, 30 (46.2%) and 39 (60%) patients showed thyroid and thymus FDG uptake, respectively. The frequency of thymus uptake FDG was high in patients younger than age 40 (28/31, 90.3%). The patterns of the thymic FDG uptake include inverted V or triangular, separated triangular, united nontriangular, unilateral right or left extension, and focal midline. Focal midline FDG uptake was the most common pattern (15/39, 38.5%). None of the control group showed thymus FDG uptake. The correlation coefficient between the FDG uptake SUV levels in thymus and serum hormones, thyrotropin, TPO Ab, TR Ab, and thymulin levels were all low (P > .05). In FDG PET scan, thymus activity was common in hyperthyroidism patients; this should not be misdiagnosed as a malignancy in patients exhibiting weight loss. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab

PubMed Central

Jansen, Yanina; Schreuer, Max; Everaert, Hendrik; Velkeniers, Brigitte; Neyns, Bart; Bravenboer, Bert

2016-01-01

Context: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. Objective: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. Design and Setting: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. Patients: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. Main Outcome Measures: Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT. Results: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. Conclusions: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. PMID:27571185

Hydrogen peroxide inhibits iodide uptake and iodine organification in cultured porcine thyroid follicles.

PubMed

Fukayama, H; Murakami, S; Nasu, M; Sugawara, M

1991-01-01

We investigated the effect of hydrogen peroxide on the process of thyroid hormone formation in a physiologic culture system of porcine thyroid follicles that we recently established. Porcine thyroid follicles cultured in medium containing 1 mU/mL TSH were exposed to 0 to 500 microM hydrogen peroxide in the presence of 0.1 microCi carrier-free Na125 and sodium iodide for 2 h. Iodide uptake and iodine organification were measured in this incubation system. The kinetics of iodide uptake were used to explain the action of hydrogen peroxide. In addition, cAMP content and Na+,K(+)-ATPase activity (an enzyme necessary for iodide uptake) were measured to investigate the mechanism of hydrogen peroxide action. Hydrogen peroxide at concentrations of 100, 200, and 500 microM inhibited iodide uptake in a dose-dependent manner. Iodide organification was inhibited only when the concentration of hydrogen peroxide was greater than 200 microM. The kinetics of iodide uptake indicated that hydrogen peroxide was a noncompetitive inhibitor with iodide. Inhibition of iodide uptake and iodine organification by hydrogen peroxide were not mediated by alteration of cAMP content of Na+,K(+)-ATPase activity, since exposure to even 500 microM hydrogen peroxide did not change these parameters in the follicle when compared with those of control samples. Our results suggest that the iodide transport system in the thyroid follicle is inhibited at 200 microM hydrogen peroxide or greater.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xuemei; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells bymore » JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.« less

Assessment of the usefulness of the standardized uptake values and the radioactivity levels for the preoperative diagnosis of thyroid cancer measured by using 18F-FDG PET/CT dual-time-point imaging

NASA Astrophysics Data System (ADS)

Lee, Hyeon-Guck; Hong, Seong-Jong; Cho, Jae-Hwan; Han, Man-Seok; Kim, Tae-Hyung; Lee, Ik-Han

2013-02-01

The purpose of this study was to assess and compare the changes in the SUV (standardized uptake value), the 18F-FDG (18F-fluorodeoxyglucose) uptake pattern, and the radioactivity level for the diagnosis of thyroid cancer via dual-time-point 18F-FDG PET/CT (positron emission tomographycomputed tomography) imaging. Moreover, the study aimed to verify the usefulness and significance of SUV values and radioactivity levels to discriminate tumor malignancy. A retrospective analysis was performed on 40 patients who received 18F-FDG PET/CT for thyroid cancer as a primary tumor. To set the background, we compared changes in values by calculating the dispersion of scattered rays in the neck area and the lung apex, and by comparing the mean and SD (standard deviation) values of the maxSUV and the radioactivity levels. According to the statistical analysis of the changes in 18F-FDG uptake for the diagnosis of thyroid cancer, a high similarity was observed with the coefficient of determination being R2 = 0.939, in the SUVs and the radioactivity levels. Moreover, similar results were observed in the assessment of tumor malignancy using dual-time-point. The quantitative analysis method for assessing tumor malignancy using radioactivity levels was neither specific nor discriminative compared to the semi-quantitative analysis method.

Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in Thyroid Male Rat Cells by Increasing Reactive Oxygen Species

PubMed Central

Arriagada, Alejandro A.; Albornoz, Eduardo; Opazo, Ma. Cecilia; Becerra, Alvaro; Vidal, Gonzalo; Fardella, Carlos; Michea, Luis; Carrasco, Nancy; Simon, Felipe; Elorza, Alvaro A.; Bueno, Susan M.; Kalergis, Alexis M.

2015-01-01

Na+/I− symporter (NIS) mediates iodide (I−) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I−. High doses of I− for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I− uptake through a reduction of NIS expression. Here we show that inhibition of I− uptake occurs as early as 2 hours or 5 hours after exposure to excess I− in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I− uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I− for 2 hours increased H2O2 generation. Furthermore, the inhibitory effect of excess I− on NIS-mediated I− transport could be recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I− inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species. PMID:25594695

Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat: in vivo studies.

EPA Science Inventory

Perchlorate, a contaminant found in food and water supplies throughout the USA, blocks iodine uptake into the thyroid gland to reduce circulating levels of thyroid hormone. Neurological function accompanying developmental exposure to perchlorate was evaluated in the present study...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willemin, Marie-Emilie; Lumen, Annie, E-mail: Anni

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, withmore » a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN{sup −}) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN{sup −} seemed to be greater than the NIS-mediated uptake. • The dose-dependent kinetics of SCN{sup −} was captured after an acute and chronic exposure. • The PBPK model of thiocyanate was successfully extrapolated to humans.« less

Struma Ovarii in Pregnancy: An Uncommon Cause of Hyperthyroidism.

PubMed

Merza, Zayd; White, Duncan; Khanem, Noor

2015-08-01

A 28-year-old woman presented with weight loss and tiredness. Investigations revealed hyperthyroidism. She was commenced on treatment and later became pregnant. Her thyroid levels remained raised, and she later underwent an elective cesarean delivery and ovarian cystectomy. Only a partial cystectomy was achieved, and histopathology examination revealed struma ovarii. An isotope uptake scan ((123)I) including her pelvis revealed low uptake in the thyroid gland and an area of high uptake in her pelvis. The cyst was subsequently removed, and within days, her thyroid hormone levels dropped. This case illustrates the importance of considering uncommon causes of hyperthyroidism.

Radioiodine therapy for thyroid cancer depicted uterine leiomyoma.

PubMed

Hirata, Kenji; Shiga, Tohru; Kubota, Kanako C; Okamoto, Shozo; Kamibayashi, Tomohito; Tamaki, Nagara

2009-03-01

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

PubMed

Okosieme, O E; Chan, D; Price, S A; Lazarus, J H; Premawardhana, L D K E

2010-01-01

The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P < 0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01). Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of Perchlorate on Thyroidal Uptake of Iodide with Corresponding Hormonal Changes

DTIC Science & Technology

2000-07-01

with iodide for uptake at this iodide-concentrating step (Goldman and Stanbury, 1973), potentially leading to hypothyroidism . As a result perchlorate...TSH can result in increased thyroid weight, goiter and hypothyroidism (Fukuda et al., 1975; Gerber et al., 1981). The objective of this study was to...2000) "• Canine T3 kits ( canine T3 calibrators batch # C3D3-8, expired July 31, 1999; 1251 canine T 3 batch #, TC32, expired July 31, 1999; canine T3

Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goitre with low radioactive iodine uptake.

PubMed

Azorín Belda, M J; Martínez Caballero, A; Figueroa Ardila, G C; Martínez Ramírez, M; Gómez Jaramillo, C A; Dolado Ardit, J I; Verdú Rico, J

Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131 I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131 I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131 I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Positron emission tomography as an aid in the diagnosis and follow-up of Riedel's thyroiditis.

PubMed

Kotilainen, Pirkko; Airas, Laura; Kojo, Tiina; Kurki, Timo; Kataja, Kaisa; Minn, Heikki; Nuutila, Pirjo

2004-06-01

We describe the usage of positron emission tomography (PET) as an aid in the initial diagnosis and follow-up of Riedel's thyroiditis. A 41-year-old patient was admitted for an enlarged and tender thyroid gland in association with severe systemic symptoms of inflammation. Imaging with fluorine-18 fluorodeoxyglucose (FDG) and PET demonstrated an intensive uptake of FDG in both lobes of the thyroid gland as an indication of severe inflammation. The diagnosis of Riedel's thyroiditis was confirmed by the histological findings of biopsy specimens taken during a palliative thyroid resection. The inflammatory symptoms and local pain dramatically disappeared after commencement of high-dose corticosteroid therapy. A follow-up PET scan after 2 weeks of corticosteroid treatment showed a 60% decrease in the uptake of FDG in the thyroid. This indicates that FDG metabolic activity can also be used to assess a patient's response to therapy in Riedel's thyroiditis.

Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

PubMed

Vattimo, A; Bertelli, P; Burroni, L

1992-01-01

Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

Role of Nuclear Medicine in the Diagnosis of Benign Thyroid Diseases.

PubMed

Garberoglio, Sara; Testori, Ornella

2016-01-01

A deep understanding of thyroid pathophysiology is the basis for diagnosing and treating benign thyroid diseases with radioactive materials, known as radiopharmaceuticals, which are introduced into the body by injection or orally. After the radiotracer administration, the patient becomes the emitting source, and several devices have been studied to detect and capture these emissions (gamma or beta-negative) and transform them into photons, parametric images, numbers and molecular information. Thyroid scintigraphy is the only technique that allows the assessment of thyroid regional function and, therefore, the detection of areas of autonomously functioning thyroid nodules. Scintigraphy visualizes the distribution of active thyroid tissue and displays the differential accumulation of radionuclides in the investigated cells, thus providing a functional map. Moreover, this technique is a fundamental tool in the clinical and surgical management of thyroid diseases, including: single thyroid nodules with a suppressed thyroid-stimulating hormone level, for which fine-needle aspiration biopsy (FNAB) is used to identify hot nodules; multinodular goiters, especially larger ones, to identify cold or indeterminate areas requiring FNAB and hot areas that do not need cytologic evaluation, and to evaluate mediastinal extension; the diagnosis of ectopic thyroid tissue; subclinical hyperthyroidism to identify occult hyperfunctioning tissue; follicular lesions to identify a functioning cellular adenoma that could be benign, although such nodules are mostly cold on scintigraphy; to distinguish low-uptake from high-uptake thyrotoxicosis, and to determine eligibility for radioiodine therapy. © 2016 S. Karger AG, Basel.

GATE based Monte Carlo simulation of planar scintigraphy to estimate the nodular dose in radioiodine therapy for autonomous thyroid adenoma.

PubMed

Hammes, Jochen; Pietrzyk, Uwe; Schmidt, Matthias; Schicha, Harald; Eschner, Wolfgang

2011-12-01

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms "Adult Female" (AF, 16ml thyroid) and "Adult Male" (AM, 19ml thyroid) were used as source regions. Nodules of 1ml and 3ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1ml nodule) to 15.3 (AM, 3ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r(2)>0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy. Copyright © 2011. Published by Elsevier GmbH.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, J.P.; Izembart, M.; Marliac, V.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

PubMed

Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

2001-12-01

Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P < 0.05), consistent with 5- to 10-fold increases in matrix NO concentration. Accordingly, mtNOS expression (75%) and activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

Cost minimization analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma.

PubMed

Grigsby, P

1998-03-01

The purpose of this study was to evaluate the utility of posttreatment total body iodine-131 (I-131) scans. The records of 63 consecutive patients with thyroid carcinoma treated with surgery and postoperative I-131 were reviewed. Patients underwent a postoperative diagnostic total body I-131 scan. Subsequently, patients received therapeutic administration of I-131. Posttreatment total body I-131 scans were performed. The postoperative diagnostic total body I-131 scans revealed uptake in the neck in all 63 patients and also demonstrated lung and mediastinal uptake in 7 patients with known sites of metastatic disease. The posttreatment total body I-131 scans also revealed neck uptake in all patients and demonstrated uptake in the lung and mediastinum in those with known metastasis to those sites. Additional foci of neck uptake were revealed on the posttreatment total body I-131 scans in six patients. Stepwise logistic regression was performed to identify prognostic factors predictive of additional foci of uptake on the posttreatment total body I-131 scans compared with the pretreatment diagnostic total body I-131 scans. Variables found to correlate significantly with additional uptake on the posttreatment total body I-131 scans were tumor size > or = 2 cm, follicular histology, and multifocal disease. Posttreatment total body I-131 scans yielded additional information in only 10% (6 of 63) of the study patient population treated with postoperative I-131 for thyroid carcinoma. Therefore, the cost, and the associated inconvenience to the patient, of performing a posttreatment total body I-131 scan can be eliminated for most patients.

The impact of iodine prophylaxis on thyroid 131-iodine uptake in the region of Krakow, Poland.

PubMed

Huszno, B; Hubalewska-Hoła, A; Bałdys-Waligórska, A; Sowa-Staszczak, A; Szybiński, Z

2003-01-01

Iodine prophylaxis was introduced in Poland in 1935. It was interrupted twice, the first time between 1939 and 1947 (due to the Second World War and its aftermath), and then between 1980 and 1986, due to the economical crisis in Poland at that time. A voluntary model of iodine prophylaxis (20 +/- 10 mg/kg of household salt) introduced in Poland in 1986, was followed by a mandatory model, implemented at the beginning of 1997, with 30 +/- 10 mg/kg of household salt. In the early sixties, in our Department of Endocrinology 24-hour iodine uptake test was introduced as a routine procedure for evaluating the thyroid gland. The reference value of this test increased in 1986 after discontinuation of iodine prophylaxis, and decreased in 1998, two years after re-implementation of the mandatory model of iodine prophylaxis. In 167 patients (147 with endemic goiter and 20 with no thyroid disturbances) examined between 1998 and 2000 the mean value of 24-hour iodine uptake was 27.3 +/- 10.4%, as compared to the mean value of 45,7 +/- 6.6 % in 1986. In patients with thyrotoxicosis the mean value of iodine uptake was 41.9% +/- 16.2 in 1999 (no.=614), 42.4% +/- 16.9 in 2000 (no.=644) and 37,7% +/- 17.2 at the beginning of 2001 (no.=328). The mean value of iodine uptake in patients with thyrotoxicosis before implementation of iodine prophylaxis was over 60%. The 24-hour thyroid radioiodine uptake test proved to be a useful indicator of changes of iodine intake in a iodine-deficient population. The data presented in this study confirm the importance and efficacy of the iodine prophylaxis introduced in Poland.

Re-induction of cell differentiation and (131)I uptake in dedifferentiated FTC-133 cell line by TSHR gene transfection.

PubMed

Feng, Fang; Wang, Hui; Hou, Shasha; Fu, Hongliang

2012-11-01

Radioiodine therapy is commonly used to treat differentiated thyroid cancer (DTC), but a major challenge is dedifferentiation of DTC with the loss of radioiodine uptake. TSHR is a key molecule regulating thyrocyte proliferation and function. This study aimed to test the therapeutic potential of TSHR in dedifferentiated DTC by gene transfection in order to restore cell differentiation and radioiodine uptake. Dedifferentiated FTC-133 (dFTC-133) cells were obtained by monoclonal culture of FTC-133 cell line after (131)I radiation. Recombinant plasmid pcDNA3.1-hTSHR was transfected into dFTC-133 cells by using Lipofectamine 2000 reagent. Immunofluorescence analysis was carried out to confirm TSHR expression and its location. Radioiodine uptake assay was thereafter investigated. mRNAs and proteins of TSHR and other thyroid differentiated markers were detected by real-time PCR and western blot respectively. Among the thyroid specific genes in dFTC-133 cells with stable low radioiodine uptake, TSHR was down-regulated most significantly compared with FTC-133. Then, after TSHR gene transfection, augmented expression of TSHR was observed in dFTC-133 cell surface and cytoplasm by immunofluorescence analysis. It was found that (125)I uptake was 2.9 times higher (t=28.63, P<.01) in cells with TSHR transfection than control. The mRNAs of TSHR, NIS, TPO and Tg were also significantly increased by 1.7 times (t=13.8, P<.05), 4 times (t=28.52, P<.05), 1.5 times (t=14.43, P<.05) and 2.2 times (t=19.83, P<.05) respectively compared with control group. Decreased TSHR expression correlated with FTC-133 ongoing dedifferentiation. TSHR transfection contributed to the re-differentiation of dedifferentiated thyroid follicular carcinoma cells. Copyright © 2012 Elsevier Inc. All rights reserved.

The continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound.

PubMed

Meller, J; Becker, W

2002-08-01

At the molecular level, the uptake of radioiodine and pertechnetate is proportional to the expression of the thyroidal sodium/iodine symporter (NIS). Qualitative and quantitative scintigraphic evaluation of the thyroid is performed with a gamma camera fitted with an on-line computer system and enables determination of the iodine uptake or the technetium uptake (TCTU) as an iodine clearance equivalent. Despite new molecular genetic insights into congenital hypothyroidism, the iodine-123 or pertechnetate scan remains the most accurate test for the detection of ectopic thyroid tissue. Following the identification of specific mutations of the genes coding for the NIS, thyroid peroxidase and pendrin, the discharge test has lost its role in establishing the diagnosis of inherited dyshormonogenesis, but it is still of value in the assessment of defect severity. In PDS mutations the test can be used to establish the diagnosis of syndromic disease. Quantitative pertechnetate scintigraphy is the most sensitive and specific technique for the diagnosis and quantification of thyroid autonomy. The method has proved to be valuable in risk stratification of spontaneous or iodine-induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy and in the evaluation of therapeutic success after definitive treatment. In iodine deficiency areas the thyroid scan remains indispensable for the functional characterisation of a thyroid nodule and is still a first-line diagnostic procedure in cases of suspected thyroid malignancy. This is especially of importance in patients with Graves' disease, among whom a relatively high prevalence of cancer has been found in cold thyroid nodules. While determination of the TCTU is without any value in the differentiation between autoimmune thyroiditis and Graves' disease in most cases, it is of substantial importance in the differentiation between hyperthyroid autoimmune thyroiditis and Graves' disease.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

PubMed

Peterson, Mark E; Guterl, Jade N; Rishniw, Mark; Broome, Michael R

2016-07-01

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland. © 2016 American College of Veterinary Radiology.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis.

PubMed

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young; Lee, Won Woo

2018-01-01

Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol ( p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake ( p = 0.004), SUVmean ( p < 0.001), SUVmax ( p = 0.002), and functional thyroid mass ( p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism ( p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 - 1.035). Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

PubMed Central

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young

2018-01-01

Objective Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Materials and Methods Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. Results All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). Conclusion Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism. PMID:29713225

Typical and atypical (silent) subacute thyroiditis in a wife and husband

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, J.; Caplan, R.H.

1978-01-01

Typical subacute thyroiditis was diagnosed in a woman. Three weeks later, signs and symptoms of hyperthyroidism developed in her husband. Although the right lobe of his thyroid gland was slightly enlarged, pain and tenderness were absent throughout the course of his illness. The free thyroxine equivalent (FTE) value and the sedimentation rate were elevated; the low uptake of radioactive iodine by the thyroid gland was consistent with ''silent'' subacute thyroiditis. We postulate that a common etiology, probably viral, was operative in both cases. Nine additional cases of hyperthyroidism with low levels of thyroidal uptake of radioactive iodine are described. Themore » thyroid glands of these patients were normal or slightly enlarged. Antithyroglobulin antibody levels determined in seven patients were not substantially elevated. The clinical course of these patients was characteristic of ''silent'' subacute thyroiditis. Although the origin of the syndrome remains unclear, the disease is self-limited and therapy, if any, is supportive.« less

Specific uptake, dissociation, and degradation of /sup 125/I-labeled insulin in isolated turtle (Chrysemys dorbigni) thyroid glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marques, M.; da Silva, R.S.; Turyn, D.

1985-11-01

Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with /sup 125/I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of bovine insulin that inhibited 50% of the /sup 125/I-insulin uptake was 2 micrograms/ml of incubation medium. Most of the radioactive material (71%) extracted from the gland, after 30 min incubation with /sup 125/I-insulin, eluted in the same position as labeled insulin on Sephadex G-50. Only 24% eluted in the salt position. After 240more » min incubation, increased amount of radioactivity appeared in the Na/sup 125/I position. When bovine insulin was added together with the labeled hormone, a substantial reduction of radioactivity was observed in the insulin and Na/sup 125/I elution positions. Dissociation studies were performed at 6 degrees in glands preincubated with /sup 125/I-insulin either at 24 or 6 degrees. The percentage of trichloroacetic acid (TCA)-soluble radioactive material in the dissociation medium increased with incubation time at both temperatures. However, the degradation activity was lower at 6 than at 24 degrees. The addition of bovine insulin to the incubation buffer containing /sup 125/I-insulin reduced the radioactive degradation products in the dissociated medium. Chloroquine or bacitracin inhibited the degradation activity. Incubation of thyroid glands with /sup 125/I-hGH or /sup 125/I-BSA showed values of uptake, dissociation, and degradation similar to those experiments in which an excess of bovine insulin was added together with the labeled hormone. Thus, by multiple criteria, such as specific uptake, dissociation, and degradation, the presence of insulin-binding sites in the turtle thyroid gland may be suggested.« less

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves’ Disease and Painless Thyroiditis

PubMed Central

Abdel Razek, Ahmed Abdel Khalek; El-Said, Amr Abd El-hamid

2017-01-01

Summary Background To assess the role of diffusion-weighted MR imaging in differentiation between Graves’ disease and painless thyroiditis. Material/Methods A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. Results There was a significant difference in the ADC value of the thyroid gland between patients and the control group (P=0.001). The mean ADC value of the thyroid gland in Graves’ disease was 2.03±0.28×10–3 mm2/sec, and in patients with painless thyroiditis 1.46±0.22×10–3 mm2/sec, respectively. There was a significant difference in the ADC values between Graves’ disease and painless thyroiditis (P=0.001). When the ADC value of 1.45×10–3 mm2/sec was used as a threshold value for differentiating Graves’ disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake (r=0.57, P=0.001 and r=0.74, P=0.001, respectively). Conclusions We concluded that ADC values of the thyroid gland can be used to differentiate Graves’ disease from painless thyroiditis in patients with untreated thyrotoxicosis. PMID:29662585

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves' Disease and Painless Thyroiditis.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Abd Allah, Sieza Samir; El-Said, Amr Abd El-Hamid

2017-01-01

To assess the role of diffusion-weighted MR imaging in differentiation between Graves' disease and painless thyroiditis. A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. There was a significant difference in the ADC value of the thyroid gland between patients and the control group ( P =0.001). The mean ADC value of the thyroid gland in Graves' disease was 2.03±0.28×10 -3 mm 2 /sec, and in patients with painless thyroiditis 1.46±0.22×10 -3 mm 2 /sec, respectively. There was a significant difference in the ADC values between Graves' disease and painless thyroiditis ( P =0.001). When the ADC value of 1.45×10 -3 mm 2 /sec was used as a threshold value for differentiating Graves' disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake ( r =0.57, P =0.001 and r =0.74, P =0.001, respectively). We concluded that ADC values of the thyroid gland can be used to differentiate Graves' disease from painless thyroiditis in patients with untreated thyrotoxicosis.

Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanders, L.R.; Moreno, A.J.; Pittman, D.L.

1986-05-01

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

[Hyperthyroidism by autonomous metastasis of thyroid carcinoma (author's transl)].

PubMed

Mornex, R; Pousset, G; Briere, J; Daumont, M; Paffoy, J C

1976-01-01

Nine years after surgical ablation of a trabeculo-vesicular carcinoma of the tyroid, a patient developped bone and liver metastasis. She had clinical signs of thyrotoxicosis, clear increase of blood T3 and sligh increase of T4. The TSH secretion was blocked. Exogenous TSH increased iodine uptake in the thyroid and not in the metastasis. After 2 doses of 120 mCi of 131I, she became hypothyroid, the liver was normal and the scan revealed the disappearance of uptake in thyroid and in metastasis. Such a clinical course was previously found in only 10 cases despite the frequent funcitonal differenciation of the metastasis of thyroid carcinomas.

Iodide handling by the thyroid epithelial cell.

PubMed

Nilsson, M

2001-01-01

Iodination of thyroglobulin, the key event in the synthesis of thyroid hormone, is an extracellular process that takes place inside the thyroid follicles at the apical membrane surface that faces the follicular lumen. The supply of iodide involves two steps of TSH-regulated transport, basolateral uptake and apical efflux, that imprint the polarized phenotype of the thyroid cell. Iodide uptake is generated by the sodium/iodide symporter present in the basolateral plasma membrane. A candidate for the apical iodide-permeating mechanism is pendrin, a chloride/iodide transporting protein recently identified in the apical membrane. In physiological conditions, transepithelial iodide transport occurs without intracellular iodination, despite the presence of large amounts of thyroglobulin and thyroperoxidase inside the cells. The reason is that hydrogen peroxide, serving as electron acceptor in iodide-protein binding and normally produced at the apical cell surface, is rapidly degraded by cytosolic glutathione peroxidase once it enters the cells. Iodinated thyroglobulin in the lumen stores not only thyroid hormone but iodine incorporated in iodotyrosine residues as well. After endocytic uptake and degradation of thyroglobulin, intracellular deiodination provides a mechanism for recycling of iodide to participate in the synthesis of new thyroid hormone at the apical cell surface.

Three-dimensional noninvasive monitoring iodine-131 uptake in the thyroid using a modified Cerenkov luminescence tomography approach.

PubMed

Hu, Zhenhua; Ma, Xiaowei; Qu, Xiaochao; Yang, Weidong; Liang, Jimin; Wang, Jing; Tian, Jie

2012-01-01

Cerenkov luminescence tomography (CLT) provides the three-dimensional (3D) radiopharmaceutical biodistribution in small living animals, which is vital to biomedical imaging. However, existing single-spectral and multispectral methods are not very efficient and effective at reconstructing the distribution of the radionuclide tracer. In this paper, we present a semi-quantitative Cerenkov radiation spectral characteristic-based source reconstruction method named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer with both encouraging reconstruction results and less acquisition and image reconstruction time. We constructed the implantation mouse model implanted with a 400 µCi Na(131)I radioactive source and the physiological mouse model received an intravenous tail injection of 400 µCi radiopharmaceutical Iodine-131 (I-131) to validate the performance of the hybrid spectral CLT and compared the reconstruction results, acquisition, and image reconstruction time with that of single-spectral and multispectral CLT. Furthermore, we performed 3D noninvasive monitoring of I-131 uptake in the thyroid and quantified I-131 uptake in vivo using hybrid spectral CLT. Results showed that the reconstruction based on the hybrid spectral CLT was more accurate in localization and quantification than using single-spectral CLT, and was more efficient in the in vivo experiment compared with multispectral CLT. Additionally, 3D visualization of longitudinal observations suggested that the reconstructed energy of I-131 uptake in the thyroid increased with acquisition time and there was a robust correlation between the reconstructed energy versus the gamma ray counts of I-131 (r(2) = 0.8240). The ex vivo biodistribution experiment further confirmed the I-131 uptake in the thyroid for hybrid spectral CLT. Results indicated that hybrid spectral CLT could be potentially used for thyroid imaging to evaluate its function and monitor its treatment for thyroid cancer.

UK audit of quantitative thyroid uptake imaging.

PubMed

Taylor, Jonathan C; Murray, Anthony W; Hall, David O; Barnfield, Mark C; O'Shaugnessy, Emma R; Carson, Kathryn J; Cullis, James; Towey, David J; Kenny, Bob

2017-07-01

A national audit of quantitative thyroid uptake imaging was conducted by the Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine in 2014/2015. The aims of the audit were to measure and assess the variability in thyroid uptake results across the UK and to compare local protocols with British Nuclear Medicine Society (BNMS) guidelines. Participants were invited through a combination of emails on a public mailbase and targeted invitations from regional co-ordinators. All participants were given a set of images from which to calculate quantitative measures and a spreadsheet for capturing results. The image data consisted of two sets of 10 anterior thyroid images, half of which were acquired after administration of Tc-pertechnetate and the other half after administration of I-iodide. Images of the administration syringes or thyroid phantoms were also included. In total, 54 participants responded to the audit. The median number of scans conducted per year was 50. A majority of centres had at least one noncompliance in comparison with BNMS guidelines. Of most concern was the widespread lack of injection-site imaging. Quantitative results showed that both intersite and intrasite variability were low for the Tc dataset. The coefficient of quartile deviation was between 0.03 and 0.13 for measurements of overall percentage uptake. Although the number of returns for the I dataset was smaller, the level of variability between participants was greater (the coefficient of quartile deviation was between 0.17 and 0.25). A UK-wide audit showed that thyroid uptake imaging is still a common test in the UK. It was found that most centres do not adhere to all aspects of the BNMS practice guidelines but that quantitative results are reasonably consistent for Tc-based scans.

Accuracy of two simple methods for estimation of thyroidal {sup 131}I kinetics for dosimetry-based treatment of Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Traino, A. C.; Xhafa, B.; Sezione di Fisica Medica, U.O. Fisica Sanitaria, Azienda Ospedaliero-Universitaria Pisana, via Roma n. 67, Pisa 56125

2009-04-15

One of the major challenges to the more widespread use of individualized, dosimetry-based radioiodine treatment of Graves' disease is the development of a reasonably fast, simple, and cost-effective method to measure thyroidal {sup 131}I kinetics in patients. Even though the fixed activity administration method does not optimize the therapy, giving often too high or too low a dose to the gland, it provides effective treatment for almost 80% of patients without consuming excessive time and resources. In this article two simple methods for the evaluation of the kinetics of {sup 131}I in the thyroid gland are presented and discussed. Themore » first is based on two measurements 4 and 24 h after a diagnostic {sup 131}I administration and the second on one measurement 4 h after such an administration and a linear correlation between this measurement and the maximum uptake in the thyroid. The thyroid absorbed dose calculated by each of the two methods is compared to that calculated by a more complete {sup 131}I kinetics evaluation, based on seven thyroid uptake measurements for 35 patients at various times after the therapy administration. There are differences in the thyroid absorbed doses between those derived by each of the two simpler methods and the ''reference'' value (derived by more complete uptake measurements following the therapeutic {sup 131}I administration), with 20% median and 40% 90-percentile differences for the first method (i.e., based on two thyroid uptake measurements at 4 and 24 h after {sup 131}I administration) and 25% median and 45% 90-percentile differences for the second method (i.e., based on one measurement at 4 h post-administration). Predictably, although relatively fast and convenient, neither of these simpler methods appears to be as accurate as thyroid dose estimates based on more complete kinetic data.« less

Computerized study with 201T1 of the cold thyroid node.

PubMed

Palermo, F; Saitta, B; Coghetto, F; Tiberio, M; Caldato, L

1982-02-01

Because of its physical and potassium-metabolic characteristics 201T1 is more suitable than 131Cs for radioisotopic studies of the cold thyroid nodule, with the further diagnostic possibility of quantitatively assessing intranodular behavior for a specific differentiation among different kinds of neoformations. Using a gamma-camera on line with a computer data processing device, sequential scintiscans were recorded for the first 20-30 min after i.v. administration of 15-20 microCi/kg of radiothallium; delayed sequences were taken at 40-60 min if intranodular uptake appeared. A quantitative appraisal was made of the differential 201T1 uptake-ratio between nodule and healthy thyroid tissue (density-index) and the multiparameter analysis of thyroid time/activity curves generated on the relative regions of interest (ROIs). This computerized study, in 120 out of 293 patients submitted to this radiothallium test, has shown a) diagnostic agreement between clinical-histological and radioisotopic findings in 76 out of 79 colloid-cystic or degenerative neoformations, in all 16 malignant and in 23 out of 25 hyperplastic benign nodules; b) significant statistical difference of the density-index in solid versus cystic but not between benign and malignant nodules; c) different 201T1 kinetics behaviour in different kinds of solid thyroid lesions with a satisfactory statistical difference of the radiothallium nodular disappearance-index.

Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine

PubMed Central

Nagarajah, James; Le, Mina; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Larson, Steven M.; Ho, Alan L.; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A.; Fagin, James A.

2016-01-01

Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer. PMID:27669459

Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine.

PubMed

Nagarajah, James; Le, Mina; Knauf, Jeffrey A; Ferrandino, Giuseppe; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Saqcena, Mahesh; Larson, Steven M; Ho, Alan L; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A; Fagin, James A

2016-11-01

Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer.

Management of thyroid carcinoma with radioactive 131I.

PubMed

Paryani, S B; Chobe, R J; Scott, W; Wells, J; Johnson, D; Kuruvilla, A; Schoeppel, S; Deshmukh, A; Miller, R; Dajani, L; Montgomery, C T; Puestow, E; Purcell, J; Roura, M; Sutton, D; Mallett, R; Peer, J

1996-08-01

To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy.

PubMed

Gao, Rui; Gao, Shan; Feng, Jinteng; Wang, Yuanbo; Zhang, Guangjian

2017-09-01

Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the Tc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

DEVELOPMENT OF AN IN VITRO RADIOACTIVE IODIDE UPTAKE ASSAY (RAIU) WITH HUMAN NIS-EXPRESSING HEK293T-EPA CELL LINE

EPA Science Inventory

Many high-throughput screening (HTPS) assays are available in the US EPA ToxCast program for estrogen and androgen pathways; only a limited number of assays exist for thyroid pathways. One potential target of thyroid-disrupting chemicals is the active uptake of iodide into the t...

The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

PubMed

Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

Is 18F-FDG PET/CT useful for distinguishing between primary thyroid lymphoma and chronic thyroiditis?

PubMed

Nakadate, Masashi; Yoshida, Katsuya; Ishii, Akihiro; Koizumi, Masayuki; Tochigi, Naobumi; Suzuki, Yoshio; Ryu, Yoshiharu; Nakagawa, Tassei; Umehara, Isao; Shibuya, Hitoshi

2013-09-01

This study aims to investigate the usefulness of (18)F-FDG PET/CT for distinguishing between primary thyroid lymphoma (PTL) and chronic thyroiditis. We retrospectively reviewed the data of 196 patients with diffuse (18)F-FDG uptake of the thyroid gland and enrolled patients who were diagnosed as having PTL or chronic thyroiditis based on the medical records, pathological findings, and laboratory data. The enrolled patients comprised 10 PTL patients (M/F = 4:6) and 51 chronic thyroiditis patients (M/F = 8:43). Images had been acquired on a PET/CT scanner at 100 minutes after intravenous injection of (18)F-FDG. The PTL group consisted of 7 patients with diffuse large B-cell lymphoma (DLBCL) and 3 with mucosa-associated lymphoid tissue (MALT) lymphoma. The maximum standardized uptake value (SUV(max)) was significantly higher in the PTL group than that in the chronic thyroiditis group (25.3 ± 8.0 and 7.4 ± 3.2, P < 0.001). On the other hand, the CT density (Hounsfield unit: HU) was significantly lower in the PTL group than that in the chronic thyroiditis group (46.1 ± 7.0 HU and 62.1 ± 6.9 HU, P < 0.001). Within the PTL group, the SUV(max) was significantly higher in the cases of DLBCL than in those of MALT lymphoma (29.0 ± 6.4 and 16.7 ± 2.3, P = 0.017). The SUV(max) was significantly higher and the CT density was significantly lower in PTL as compared with those in chronic thyroiditis. Thus, (18)F-FDG PET/CT may be useful for distinguishing between PTL and chronic thyroiditis.

MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

EPA Science Inventory

The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.

PubMed

Schwartz, Frederik; Bergmann, Natasha; Zerahn, Bo; Faber, Jens

2013-04-01

Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Automated MicroSPECT/MicroCT Image Analysis of the Mouse Thyroid Gland.

PubMed

Cheng, Peng; Hollingsworth, Brynn; Scarberry, Daniel; Shen, Daniel H; Powell, Kimerly; Smart, Sean C; Beech, John; Sheng, Xiaochao; Kirschner, Lawrence S; Menq, Chia-Hsiang; Jhiang, Sissy M

2017-11-01

The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve 131 I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer. A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post injection of 123 I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively. FVB/N mice with normal thyroid glands and TgBRAF V600E mice with thyroid tumors were imaged. In-house CTViewer software was developed to streamline image analysis with new capabilities, along with display of 3D voxel-based 123 I gamma photon intensity in MATLAB. The customized mouse cradle facilitates consistent tissue configuration among image acquisitions such that rigid body registration can be applied to align serial images of the same mouse via the in-house CTViewer software. CTViewer is designed specifically to streamline SPECT/CT image analysis with functions tailored to quantify thyroid radioiodine uptake. Automatic segmentation of thyroid volumes of interest (VOI) from adjacent salivary glands in t1 images is enabled by superimposing the thyroid VOI from the t24 image onto the corresponding aligned t1 image. The extent of heterogeneity in 123 I accumulation within thyroid VOIs can be visualized by 3D display of voxel-based 123 I gamma photon intensity. MicroSPECT/CT image acquisition and analysis for thyroidal RAI uptake is greatly improved by the cradle and the CTViewer software, respectively. Furthermore, the approach of superimposing thyroid VOIs from t24 images to select thyroid VOIs on corresponding aligned t1 images can be applied to studies in which the target tissue has differential radiotracer retention from surrounding tissues.

Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated thyroid carcinoma for determining the feasibility of peptide receptor radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for peptide receptor radionuclide therapy and evidence of chromogranin A level-positive neuroendocrine differentiation.

PubMed

Jois, Bhargavi; Asopa, Ramesh; Basu, Sandip

2014-06-01

The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin level was noted in one of the patients, and the other patient was lost to follow-up. Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is observed in a relatively low fraction of patients that could favor the feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking into account that no treatment exists in this group, somatostatin receptor-targeted imaging can be an alternative diagnostic modality in the therapeutic decision making with peptide receptor radionuclide therapy and monitoring. The documentation of elevated serum chromogranin A level in 3 patients with intense tracer uptake could suggest a possible neuroendocrine differentiation in the affected tissues leading to the expression of chromogranin A along with SSTR-avid expression. This observation needs to be explored in future studies. No definite conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy in this group at present, and more prospective research is required in this area.

Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

PubMed

D'Arcy, R; McDonnell, M; Spence, K; Courtney, C H

2017-01-01

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T 4 ). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T 3 ) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging ( 123 I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T 3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. Free tri-iodothyronine (T 3 ) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T 4 ) or T 3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a patient with minimally invasive follicular carcinoma of thyroid.

PubMed

Malhotra, Gaurav; Nair, Narendra; Menon, Hari; Gujral, Sumit; Abhyankar, Amit; Baghel, Nawab S; Awasare, Sushama; Nabar, Swapna J; Abhyankar, Suman; Kand, Purushottam G

2008-01-01

A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass. Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion continued to show I-131 uptake even while on daily T3 substitution, suggesting that the mass was thyroid stimulating hormone-independent. Because the mass showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat with I-131. He was continued on T3 substitution therapy and was given 209 mCi of I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests the possibility of this therapeutic option in nonthyroidal tumors that may concentrate radioiodine.

Late 124I PET/CT Uptake Measurement-Assessment of Appropriate Examination Protocol in Benign Thyroid Diseases.

PubMed

Freesmeyer, Martin; Gabler, Anja S; Kühnel, Christian; Winkens, Thomas

2017-07-01

This study aimed at investigating the performance of late I PET/CT for radioiodine uptake (RAIU) measurement at 336 hours after administration in patients with benign thyroid diseases requiring radioiodine therapy. Special attention was paid to the comparability of I uptake (I-RAIU) to the clinical standard (I-RAIU, probe measurement). Considering cost aspects, we sought to establish an economically reasonable examination protocol based on scan duration and administered activity. List-mode PET data sets of 40-minute acquisition time were acquired 336 hours after administration of 1 MBq I in 18 patients. Different scan durations were simulated by different reconstruction intervals (RIs) ranging from 5 seconds to 40 minutes, and total thyroid activity was measured. Mean I-RAIU levels of each RI were compared with mean I-RAIU levels (3 MBq). A hypothetical scan duration or hypothetical activity, respectively, was sought by means of a proportion equation, considering that the length of an RI is equitable to a hypothetical activity. After 336 hours, the mean total thyroid activity was 254 ± 7.7 kBq for I and 26.9 ± 8.7 kBq for I. The mean I-RAIU and I-RAIU showed high levels of agreement for RI from 2 minutes to 40 minutes. Reconstruction interval shorter than 2 minutes did not result in sufficient agreement. The present study confirmed the feasibility of late I PET/CT as alternative method for RAIU measurement in patients with benign thyroid diseases; 1 MBq I PET/CT scans as short as 2 minutes resulted in RAIU levels comparable to those of standard I-RAIU. The parameter "appropriate scan-duration activity product" is proposed to enable an economically reasonable examination protocol.

Inter- and intraobserver variability of (semi-)quantitative parameters commonly used in feline thyroid scintigraphy.

PubMed

Volckaert, Veerle; Vandermeulen, Eva; Duchateau, Luc; Saunders, Jimmy H; Peremans, Kathelijne

2016-04-01

The aim of this study was to assess inter- and intraobserver variability of commonly used semi-quantitative and quantitative parameters in feline thyroid scintigraphy: thyroid to salivary gland ratio (T/S), thyroid to background ratio (T/B) and the percentage technetium pertechnetate uptake for the thyroid glands (%TcUT). These parameters are being used to diagnose thyroid disease and to assess its severity, but may be influenced by operator related factors when processing the images. Additionally, inter- and intraobserver variability of the percentage technetium pertechnetate uptake for the salivary glands was determined (%TcUSG). The study included technetium pertechnetate scans of 100 hyperthyroid cats. Variability within and between three observers was determined using a random effects model and variance components were estimated by the restricted maximum likelihood procedure. The %TcU for the thyroid and salivary glands, as well as the T/S ratio, showed little to no difference in inter- and intraobserver variability, whereas this was clearly present for the T/B ratio. Overall, the T/S ratio and %TcUSG showed a good repeatability and reproducibility with low inter- and intraobserver variabilities. Inter- and intraobserver variability was higher for the %TcUT, however variations were still considered to be acceptable. On the contrary, inter- and intraobserver variability was clearly larger for the T/B ratio. These findings suggest the preferential use of the T/S ratio or %TcU, especially in facilities with a less experienced staff. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

PubMed

Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

2006-11-10

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

Three-dimensional Noninvasive Monitoring Iodine-131 Uptake in the Thyroid Using a Modified Cerenkov Luminescence Tomography Approach

PubMed Central

Qu, Xiaochao; Yang, Weidong; Liang, Jimin; Wang, Jing; Tian, Jie

2012-01-01

Background Cerenkov luminescence tomography (CLT) provides the three-dimensional (3D) radiopharmaceutical biodistribution in small living animals, which is vital to biomedical imaging. However, existing single-spectral and multispectral methods are not very efficient and effective at reconstructing the distribution of the radionuclide tracer. In this paper, we present a semi-quantitative Cerenkov radiation spectral characteristic-based source reconstruction method named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer with both encouraging reconstruction results and less acquisition and image reconstruction time. Methodology/Principal Findings We constructed the implantation mouse model implanted with a 400 µCi Na131I radioactive source and the physiological mouse model received an intravenous tail injection of 400 µCi radiopharmaceutical Iodine-131 (I-131) to validate the performance of the hybrid spectral CLT and compared the reconstruction results, acquisition, and image reconstruction time with that of single-spectral and multispectral CLT. Furthermore, we performed 3D noninvasive monitoring of I-131 uptake in the thyroid and quantified I-131 uptake in vivo using hybrid spectral CLT. Results showed that the reconstruction based on the hybrid spectral CLT was more accurate in localization and quantification than using single-spectral CLT, and was more efficient in the in vivo experiment compared with multispectral CLT. Additionally, 3D visualization of longitudinal observations suggested that the reconstructed energy of I-131 uptake in the thyroid increased with acquisition time and there was a robust correlation between the reconstructed energy versus the gamma ray counts of I-131 (). The ex vivo biodistribution experiment further confirmed the I-131 uptake in the thyroid for hybrid spectral CLT. Conclusions/Significance Results indicated that hybrid spectral CLT could be potentially used for thyroid imaging to evaluate its function and monitor its treatment for thyroid cancer. PMID:22629431

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

PubMed

Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study.

PubMed

Ceccarelli, Claudia; Bencivelli, Walter; Vitti, Paolo; Grasso, Lucia; Pinchera, Aldo

2005-03-01

To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules. Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years. A total of 346 patients treated with 131I in the years 1975-95, for a single hyperfunctioning nodule. Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism. The cumulative incidence of hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0.01), 24-th 131I uptake (P < 0.05) and previous treatment with methimazole (MMI, P < 0.1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0.01). After 20 years of follow-up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.

Effects of 3-nitro-l-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect

PubMed Central

Green, William L.

1971-01-01

The effects on thyroid function of an inhibitor of tyrosine dehalogenase, 3-nitro-L-tyrosine (MNT) have been investigated in rats. In preliminary studies, marked inhibition of iodotyrosine deiodination was demonstrated in rats drinking 8 mM MNT. A series of experiments was then performed in which rats received Remington low iodine diet and 8 mM MNT as drinking fluid. This regimen had the following effects, compared to the effects of a low iodine diet alone: (a) a decrease in serum protein-bound iodine, elevation of serum thyrotropin level, goiter, and growth inhibition all prevented or reversed by iodine supplements: (b) on initiation of MNT, a 2- to 3-fold increase in the rate of release of radioiodine from the thyroid and concomitant urinary excretion of large amounts of organic iodine: and (c) after 2 wk of MNT, a greatly increased rate of thyroidal uptake and release of 131I, an increase in the ratio of monoiodotyrosine-131I to diiodotyrosine-131I in thyroid proteolysates and the appearance of labeled iodotyrosines in serum. Acute administration of MNT intraperitoneally to rats on either an iodine-deficient or iodine-sufficient diet did not inhibit thyroidal uptake of 131I or alter the distribution of 131I among thyroidal iodoamino acids. It is concluded that MNT is an effective inhibitor of iodotyrosine deiodination in vivo, without other important actions on thyroid function. Thus, MNT treatment affords a model for the human dehalogenase defect. By provoking iodotyrosine secretion and consequent urinary loss of iodine, MNT can exaggerate the effects of a low iodine intake, producing goitrous hypothyroidism despite a rapid rate of iodine turnover in the thyroid. Images PMID:5129302

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice.

PubMed

Schmohl, Kathrin A; Müller, Andrea M; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J; Spitzweg, Christine

2015-09-01

Due to the high variance in available protocols on iodide-131 ((131)I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of (131)I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and (99m)Tc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) (131)I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) (131)I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high (131)I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) (131)I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. (99m)Tc-pertechnetate scintigraphy revealed absence of thyroidal (99m)Tc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

PubMed Central

Schmohl, Kathrin A.; Müller, Andrea M.; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J.; Spitzweg, Christine

2015-01-01

Due to the high variance in available protocols on iodide-131 (131I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of 131I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and 99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) 131I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) 131I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high 131I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) 131I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. 99mTc-pertechnetate scintigraphy revealed absence of thyroidal 99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene. PMID:26601076

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

High-Throughput Screening and Quantitative Chemical Ranking for Sodium-Iodide Symporter Inhibitors in ToxCast Phase I Chemical Library.

PubMed

Wang, Jun; Hallinger, Daniel R; Murr, Ashley S; Buckalew, Angela R; Simmons, Steven O; Laws, Susan C; Stoker, Tammy E

2018-05-01

Thyroid uptake of iodide via the sodium-iodide symporter (NIS) is the first step in the biosynthesis of thyroid hormones that are critical for health and development in humans and wildlife. Despite having long been a known target of endocrine disrupting chemicals such as perchlorate, information regarding NIS inhibition activity is still unavailable for the vast majority of environmental chemicals. This study applied a previously validated high-throughput approach to screen for NIS inhibitors in the ToxCast phase I library, representing 293 important environmental chemicals. Here 310 blinded samples were screened in a tiered-approach using an initial single-concentration (100 μM) radioactive-iodide uptake (RAIU) assay, followed by 169 samples further evaluated in multi-concentration (0.001 μM-100 μM) testing in parallel RAIU and cell viability assays. A novel chemical ranking system that incorporates multi-concentration RAIU and cytotoxicity responses was also developed as a standardized method for chemical prioritization in current and future screenings. Representative chemical responses and thyroid effects of high-ranking chemicals are further discussed. This study significantly expands current knowledge of NIS inhibition potential in environmental chemicals and provides critical support to U.S. EPA's Endocrine Disruptor Screening Program (EDSP) initiative to expand coverage of thyroid molecular targets, as well as the development of thyroid adverse outcome pathways (AOPs).

Thyroid Carcinoma

PubMed

Ahmed, Najeeb; Niyaz, Kashif; Borakati, Aditya; Marafi, Fahad; Birk, Rubinder; Usmani, Sharjeel

2018-02-26

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice. Creative Commons Attribution License

Struma Ovarii With Hyperthyroidism.

PubMed

Ang, Lynn P; Avram, Anca M; Lieberman, Richard W; Esfandiari, Nazanene H

2017-06-01

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar I-WBS for diagnosis of extrathyroidal thyrotoxicosis.

Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

PubMed

Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

2018-07-01

Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Bexarotene via CBP/p300 induces suppression of NF-κB-dependent cell growth and invasion in thyroid cancer.

PubMed

Cras, Audrey; Politis, Béatrice; Balitrand, Nicole; Darsin-Bettinger, Diane; Boelle, Pierre Yves; Cassinat, Bruno; Toubert, Marie-Elisabeth; Chomienne, Christine

2012-01-15

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway. ©2011 AACR.

Radionuclide thyroid imaging in the newborn with suspected hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoosufani, Z.; Karimeddini, M.K.; Spencer, R.P.

1985-05-01

The authors reviewed their experience with thyroid imaging in newborns with suspected congenital hypothyroidism. The infants were selected through a hypothyroidism screening program. There were 19 infants (14 females, 5 males) from 2 to 8 weeks of age with a blood T4 <6 ..mu..g/dl. Thyroid imaging was performed with either IV or IM injection of 0.5 to 1 mCi of Tc 99m pertechnetate using a gamma camera with a pinhole collimator. Salivary glands and stomach were also imaged for assessing the presence of the transport system. In 6 infants (32%) no thyroid tissue was visualized (thyroid hypoplasia). Four infants (21%)more » showed ectopic thyroid tissue in the lingual or sublingual area. Two infants (10%) had evidence of goiter. The remaining 7 infants (37%) had normal appearing glands in size and position. TSH values were markedly elevated (> 100 ..mu mu../ml) in all 10 patients with hypoplastic or ectopic thyroid. Two patients were subsequently found to have normal thyroid function (one with TBG deficiency and one with transient hypothyroidism). Thyroidal as well as salivary gland trapping of the radiotracer in these two infants was clearly less than that of adults suggesting immaturity of the transport/trapping mechanism. All 4 patients with ectopic thyroid had markedly increased uptake of the radiotracer. All other patients with elevated TSH levels had increased uptake of the radiotracer as compared to the normals. They conclude that thyroid scanning is an important tool in delineating the etiology of congenital hypothyroidism.« less

Whole-body scintigraphy with radioiodine-131. A comprehensive list of false-positives with some examples.

PubMed

McDougall, I R

1995-10-01

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michigishi, T.; Mizukami, Y.; Mura, T.

1991-05-01

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

A Case of Severe and Recurrent Painless Thyroiditis Requiring Thyroidectomy

PubMed Central

Ishii, Hiroaki; Takei, Masahiro; Sato, Yoshihiko; Ito, Tokiko; Ito, Ken-ichi; Sakai, Yasuhiro; Yumita, Wataru; Suzuki, Satoru; Komatsu, Mitsuhisa

2013-01-01

Objective To report a case of severe and recurrent painless thyroiditis requiring thyroidectomy. Clinical Presentation and Intervention A 47-year-old man who presented with severe thyrotoxicosis was found to have extremely low radioactive iodine uptake, negative TSH receptor antibodies, and normal C-reactive protein; these findings suggested a diagnosis of painless thyroiditis. Due to the severity and recurrence of thyrotoxicosis, surgical resection of the thyroid gland was performed to prevent a thyrotoxic storm. Histological examination revealed typical lymphoid infiltration of the thyroid gland. Conclusion This case illustrates that a patient with painless thyroiditis was successfully treated with surgery. PMID:23182952

Transient thyrotoxicosis from thyroiditis induced by sibutramine overdose: a case report.

PubMed

Kim, S K; Lee, S M; Yoo, S S; Hahm, J R; Jung, J H; Kim, H S; Kim, S; Chung, S I; Jung, T S

2013-08-01

Sibutramine is an antiobesity drug that inhibits the reuptake of serotonin and noradrenalin in the hypothalamus. A 37-year-old Korean man presented to the emergency room for the oral intake of 280 mg of sibutramine. The patient was in thyrotoxic state. The (99m)Technetium-pertechnetate thyroid scan showed irregular uptake of radioisotope and thyroid-stimulating hormone receptor antibody and thyroperoxidase antibody were negative. Thyroid function normalized after that. The patient had transient thyrotoxicosis with thyroiditis. We report a case of thyrotoxicosis accompanied by thyroiditis resulting from the intentional overdose of sibutramine.

Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer.

PubMed

Ocak, Meltem; Demirci, Emre; Kabasakal, Levent; Aygun, Aslan; Tutar, Rumeysa O; Araman, Ahmet; Kanmaz, Bedii

2013-11-01

Somatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. Thirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. Both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, P<0.001), respectively. Our study suggested that Ga-68 DOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.

[Sub-acute thyroiditis in a patient on immunosuppressive treatment].

PubMed

D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

2013-01-01

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

Thyroid axis disruption in juvenile brown trout (Salmo trutta) exposed to the flame retardant β-tetrabromoethylcyclohexane (β-TBECH) via the diet.

PubMed

Park, Bradley J; Palace, Vince; Wautier, Kerry; Gemmill, Bonnie; Tomy, Gregg

2011-09-15

Tetrabromoethylcyclohexane (TBECH) is an additive brominated flame retardant used in domestic and industrial applications. It has been detected in wildlife, and there is early evidence that it is an endocrine disruptor. Whereas other brominated flame retardants with similar physicochemical properties have been shown to disrupt the thyroid axis, no such evaluation has been conducted for TBECH. To elucidate this, juvenile brown trout (Salmo trutta) were fed either a control diet or diets containing low, medium, or high doses of β-TBECH, the isomer most frequently detected in wildlife, for 56 days (uptake phase) followed by a control diet for an additional 77 days (depuration phase). Eight fish per treatment were lethally sampled on uptake days 7, 14, 21, 35, 49, and 56 and on depuration days 7, 21, 35, 49, and 77 to assess fish condition, circulating free and total triiodothyronine and thyroxine, and thyroid epithelial cell height. Although there was no effect on condition factor, there was a significant reduction in total plasma thyroxine in the high dose group and a significant increase in mean thyroid epithelial cell height in the low, medium, and high dose groups during the uptake phase, whereas there were no differences in the depuration phase. These results indicate that β-TBECH may modulate the thyroid axis in fish at environmentally relevant concentrations.

Evaluation of 99mTc-MIBI in thyroid gland imaging for the diagnosis of amiodarone-induced thyrotoxicosis

PubMed Central

Zhang, Ruiguo

2017-01-01

Objective: Amiodarone-induced thyrotoxicosis (AIT) is caused by amiodarone as a side effect of cardiovascular disease treatment. Based on the differences in their pathological and physiological mechanisms, many methods have been developed so far to differentiate AIT subtypes such as colour flow Doppler sonography (CFDS) and 24-h radioiodine uptake (RAIU). However, these methods suffer from inadequate accuracy in distinguishing different types of AITs and sometimes lead to misdiagnosis and delayed treatments. Therefore, there is an unmet demand for an efficient method for accurate classification of AIT. Methods: Technetium-99 methoxyisobutylisonitrile (99mTc-MIBI) thyroid imaging was performed on 15 patients for AIT classification, and the results were compared with other conventional methods such as CFDS, RAIU and 99mTcO4 imaging. Results: High uptake and retention of MIBI in thyroid tissue is characteristic in Type I AIT, while in sharp contrast, low uptake of MIBI in the thyroid tissue was observed in Type II AIT. Mixed-type AIT shows uptake value between Types I and II. MIBI imaging outperforms other methods with a lower misdiagnosis rate. Conclusion: Among the methods evaluated, MIBI imaging enables an accurate identification of Type I, II and mixed-type AITs by showing distinct images for different types of AITs. The results obtained from our selected subjects revealed that MIBI imaging is a reliable method for diagnosis and classification of AITs and MIBI imaging has potential in the treatment of thyroid diseases. Advances in knowledge: 99mTc-MIBI imaging is a useful method for the diagnosis of AIT. It can distinguish different types of AITs especially for mixed-type AIT, which is usually difficult to treat. 99mTc-MIBI has potential advantages over conventional methods in the efficient treatment of AIT. PMID:28106465

The Clinical and Thyroid Function Studies of Lymphocytic Thyroiditis with Spontaneously Resolving Hyperthyroidism: Comparison to Subacute Thyroiditis

PubMed Central

Koh, Eun Hee; Park, Yong Joon; Lee, Hyun Chul; Hong, Chein Soo; Huh, Kap Bum; Lee, Sang Yong; Ryu, Kyung Za

1986-01-01

Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH) has been reported in the past years, and is referred to as “silent thyroiditis.” It is characterized by a low or decreased radioactive iodine uptake (RAIU) of thyroid in a patient with hyperthyroidism in whom initial diagnosis is generally thought to be Graves’ disease. Thirty-five patients who had hyperthyroidism or goiter with decreased RAIU have been assessed. Twenty-four (68.6%) of 35 patients had LT-SRH and the remaining patients, subacute thyroiditis (SAT). The clinical characteristics of the patients with LT-SRH were a history of delivery, painless goiter, elevated T3 and T4 levels and positive anti-microsomal antibodies. Anti-microsomal antibodies were positive in 70.8% of the LT-SRH group, whereas 12.5% in the SAT group. Resolution of the hyperthyroidism took 8 to 12 months. It is considered that LT-SRH is an autoimmune thyroiditis with spontaneously resolving hyperthyroidism and determination of the RAIU is very useful in differentiating from other forms of hyperthyroidism. PMID:15759376

Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

PubMed Central

Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete

2016-01-01

Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to have more aggressive biological course and need early detection and other kind of treatment. PMID:27703298

Optimization of (131)I doses for the treatment of hyperthyroidism.

PubMed

Araujo, F; Rebelo, A M O; Pereira, A C; Moura, M B; Lucena, E A; Dantas, A L A; Dantas, B M; Corbo, R

2009-11-15

Several methods can be used to determine the activity of (131)I in the treatment of hyperthyroidism. However, many of them do not consider all the parameters necessary for optimum dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: organ mass, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with (131)I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the IRD was used to calibrate a scintillation camera and a uptake probe SCT-13004 at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and a uptake probe SCT-13002, available at the Nuclear Medicine Institute in Goiânia. The biokinetic parameters were determined based on measurements performed in eight voluntary patients. It is concluded that the use of the equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable and feasible procedure for dose optimization in terms of effectiveness, simplicity and cost.

21 CFR 862.1715 - Triiodothyronine uptake test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid...

21 CFR 862.1715 - Triiodothyronine uptake test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid...

21 CFR 862.1715 - Triiodothyronine uptake test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid...

21 CFR 862.1715 - Triiodothyronine uptake test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid...

21 CFR 862.1715 - Triiodothyronine uptake test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid...

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

PubMed Central

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

Thyroid Scan and Uptake

MedlinePlus

... minutes prior to the test. When it is time for the imaging to begin, you will lie down on a moveable examination table with your head tipped backward and neck extended. The gamma camera will then take a series of images, capturing images of the thyroid gland ...

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

PubMed

Bailey, J J; Dewaraja, Y; Hubers, D; Srinivasa, R N; Frey, K A

2017-10-01

To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Reevaluation of the thyroidal radioactive iodine uptake test, with special reference to reversible primary hypothyroidism with elevated thyroid radioiodine uptake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamura, K.; Sato, K.; Ikenoue, H.

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidismmore » was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.« less

Correlation between thyroidal and peripheral blood total T cells, CD8+ T cells, and CD8+ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves' ophthalmopathy.

PubMed

Al-Ansari, Farah; Lahooti, Hooshang; Stokes, Leanne; Edirimanne, Senarath; Wall, Jack

2018-05-22

Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 +  T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. We found a positive correlation between thyroidal CD8 +  T cells and CD8 +  T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. Our observations provide further evidence for a possible role of thyroidal CD8 +  T cells, CD8 +  T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.

Subacute Thyroiditis: Clinical Presentation and Long Term Outcome

PubMed Central

Alfadda, Assim A.; Sallam, Reem M.; Elawad, Ghadi E.; AlDhukair, Hisham; Alyahya, Mossaed M.

2014-01-01

Few studies have been reported from the Kingdom of Saudi Arabia (SA) to describe the clinical presentation and long term outcomes of subacute thyroiditis (SAT). Our aim was to review the demographic, anthropometric, clinical presentation, laboratory results, treatment, and disease outcome in Riyadh region and to compare those with results from different regions of the Kingdom and different parts of the world. We reviewed the medical files of patients who underwent thyroid uptake scan during an 8-year period in King Khalid University Hospital. Only 25 patients had confirmed diagnosis of thyroiditis. Age and gender distribution were similar to other studies. Most patients presented with palpitation, goiter, and weight change. Elevated thyroid hormones, suppressed thyroid-stimulating hormone, and elevated ESR were reported. Among those, 7 cases of SAT were recorded. β-Blockers were prescribed to 57% and nonsteroidal anti-inflammatory drugs to 29% of SAT. Long follow-up demonstrated that 85.7% of SAT cases recovered, while 14.3% developed permanent hypothyroidism. In conclusion, SAT is uncommon in the central region of SA. Compared to the western region, corticosteroid is not commonly prescribed, and permanent hypothyroidism is not uncommon. A nation-wide epidemiological study to explain these interprovincial differences is warranted. PMID:24803929

Modulation of thyroidal radioiodide uptake by oncological pipeline inhibitors and Apigenin.

PubMed

Lakshmanan, Aparna; Scarberry, Daniel; Green, Jill A; Zhang, Xiaoli; Selmi-Ruby, Samia; Jhiang, Sissy M

2015-10-13

Targeted radioiodine therapy for thyroid cancer is based on selective stimulation of Na+/I- Symporter (NIS)-mediated radioactive iodide uptake (RAIU) in thyroid cells by thyrotropin. Patients with advanced thyroid cancer do not benefit from radioiodine therapy due to reduced or absent NIS expression. To identify inhibitors that can be readily translated into clinical care, we examined oncological pipeline inhibitors targeting Akt, MEK, PI3K, Hsp90 or BRAF in their ability to increase RAIU in thyroid cells expressing BRAFV600E or RET/PTC3 oncogene. Our data showed that (1) PI3K inhibitor GDC-0941 outperformed other inhibitors in RAIU increase mainly by decreasing iodide efflux rate to a great extent; (2) RAIU increase by all inhibitors was extensively reduced by TGF-β, a cytokine secreted in the invasive fronts of thyroid cancers; (3) RAIU reduction by TGF-β was mainly mediated by NIS reduction and could be reversed by Apigenin, a plant-derived flavonoid; and (4) In the presence of TGF-β, GDC-0941 with Apigenin co-treatment had the highest RAIU level in both BRAFV600E expressing cells and RET/PTC3 expressing cells. Taken together, Apigenin may serve as a dietary supplement along with small molecule inhibitors to improve radioiodine therapeutic efficacy on invasive tumor margins thereby minimizing future metastatic events.

A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy.

PubMed

Aoyama, Mariko; Takizawa, Hiromitsu; Tsuboi, Mitsuhiro; Nakagawa, Yasushi; Tangoku, Akira

2017-12-28

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.

Tc-99m imaging in thyroidectomized differentiated thyroid cancer patients immediately before I-131 treatment.

PubMed

Tsai, Chi-Jung; Cheng, Cheng-Yi; Shen, Daniel Hueng-Yuan; Kuo, Shou Jen; Wang, Lien-Yen; Lee, Chiang-Hsuan; Wang, Jhi-Joung; Chang, Ming-Che; Huang, Wen-Sheng

2016-02-01

The aim of this study was to evaluate the clinical role of technetium-99m pertechnetate (Tc-99m) imaging in thyroidectomized differentiated thyroid cancer patients immediately before radioiodine-131 (I-131) treatment (Tx). Eighty-six consecutive post-total-thyroidectomy patients (15 men, 71 women; mean age: 46.8 years) with pathologically diagnosed differentiated thyroid cancer were retrospectively studied. Tc-99m imaging immediately before I-131 Tx using both patient-based and lesion-based measurements were analyzed and were further compared with those of post-Tx I-131 whole-body scans. For patients with unequivocally positive Tc-99m uptake, the sensitivity was 77% (patient-based) and 59% (site-based). The positive predictive value (PPV) was 100% for both patient-based and site-based measurements. If equivocal Tc-99m uptake was counted as positive, the sensitivity was 83 and 67%, and the PPV was 100 and 99% for patient-based and site-based measurements, respectively. (a) To increase sensitivity yet maintaining high PPV, equivocal Tc-99m uptake should be considered a positive finding. (b) The nearly 100% PPV of Tc-99m imaging immediately before I-131 Tx for remnant detection suggests that Tc-99m imaging not only serves as an alternative to low-dose I-131 scanning in the low-risk post-thyroidectomy patients but also provides a clue for the subsequent I-131 therapeutic dosage and even for the outcome prediction.

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

PubMed

Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

1999-01-15

Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.

Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Jeffrey; Almarzouki, Hani; Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah

Purpose: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. Methods and Materials: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection,more » hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. Results: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. Conclusions: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. This technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.« less

Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?

PubMed Central

Beyer, S.J.; Jimenez, R.E.; Shapiro, C.L.; Cho, J.Y.; Jhiang, S.M.

2009-01-01

The Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized. PMID:18500672

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site.

PubMed

Gold, Ellen B; Blount, Benjamin C; O'Neill Rasor, Marianne; Lee, Jennifer S; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-07-01

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Hyperfunctioning solid/trabecular follicular carcinoma of the thyroid gland.

PubMed

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the (99m)Tc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

The utility of indocyanine green near infrared fluorescent imaging in the identification of parathyroid glands during surgery for primary hyperparathyroidism.

PubMed

Zaidi, Nisar; Bucak, Emre; Okoh, Alexis; Yazici, Pinar; Yigitbas, Hakan; Berber, Eren

2016-06-01

Intraoperative adjuncts for the localization of parathyroid glands in parathyroid surgery are limited. The aim of this study is to assess the usefulness of indocyanine green (ICG) near-infrared (NIR) fluorescent imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT). ICG imaging was performed in 33 patients undergoing parathyroidectomy (PTX). Thyroid and parathyroid ICG uptake were assessed and independently verified on a grading scale. Clinical variables were recorded and analyzed for factors associated with ICG uptake. Of 112 glands identified by naked eye, 104 (92.9%) demonstrated ICG uptake. Concomitant ICG fluorescence was identified in the thyroid in all patients. There was a trend toward increased ICG fluorescence in patients <60 years of age (P = 0.05). A higher degree of fluorescence was seen in patients presenting with pre-operative calcium values >11 mg/dl (P = 0.04) and in those parathyroids larger than 10 mm (P < 0.01). All patients had biochemically proven cure. No patients who underwent subtotal PTX (n = 6) developed postoperative hypoparathyroidism. ICG can reliably localize parathyroid glands during PTX and additionally allow for assessment of parathyroid perfusion in patients undergoing subtotal resection. Concomitant fluorescence of the thyroid gland limits ICG's usefulness in directing the course of PTX. J. Surg. Oncol. 2016;113:771-774. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

PubMed

Delivanis, Danae A; Gustafson, Michael P; Bornschlegl, Svetlana; Merten, Michele M; Kottschade, Lisa; Withers, Sarah; Dietz, Allan B; Ryder, Mabel

2017-08-01

Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Single-center, retrospective cohort study. We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment. Copyright © 2017 Endocrine Society

False-positive iodine-131 whole-body scan findings in patients with differentiated thyroid carcinoma: report of 11 cases and review of the literature.

PubMed

Buton, Leckzinscka; Morel, Olivier; Gault, Patricia; Illouz, Frédéric; Rodien, Patrice; Rohmer, Vincent

2013-07-01

Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

PubMed

Monzani, F; Del Guerra, P; Caraccio, N; Casolaro, A; Lippolis, P V; Goletti, O

1997-05-01

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

[Poorly differentiated thyroid carcinomas: new therapeutic considerations].

PubMed

Graf, Hans

2005-10-01

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

PubMed Central

Liu, Yu-Yu; Brandt, Michael P; Shen, Daniel H; Kloos, Richard T; Zhang, Xiaoli; Jhiang, Sissy M

2014-01-01

Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T3)-supplemented mice was much less than that in mice received neither bTSH nor T3 (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model. PMID:20943721

Percutaneous ethanol injection of hyperfunctioning thyroid nodules: long-term follow-up in 125 patients.

PubMed

Tarantino, Luciano; Francica, Giampiero; Sordelli, Ignazio; Sperlongano, Pasquale; Parmeggiani, Domenico; Ripa, Carmine; Parmeggiani, Umberto

2008-03-01

The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules < or = 10 mL, 63 (94.0%) of 67; nodules > 10 to < or = 30 mL, 32 (91.4%) of 35; nodules > 30 to < or = 60 mL, 17 (89.5%) of 19; nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months' follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up. PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

NASA Astrophysics Data System (ADS)

Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

2001-11-01

Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

Predictive value of tracer studies for /sup 131/I treatment in hyperthyroid cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broome, M.R.; Turrel, J.M.; Hays, M.T.

In 76 cats with hyperthyroidism, peak thyroidal radioiodine (/sup 131/I) uptakes and effective half-lives were determined after administration of tracer and therapeutic activities of /sup 131/I. In 6 additional hyperthyroid cats, only peak thyroidal uptakes after administration of tracer and therapeutic activities of /sup 131/I were determined. Good correlation was found between peak thyroidal uptakes of tracer and therapeutic /sup 131/I; however, only fair correlation was observed between effective half-lives. In 79% of the cats, the effective half-life for therapeutic /sup 131/I was longer than that for tracer /sup 131/I. After administration of therapeutic activity of /sup 131/I, monoexponential andmore » biphasic decay curves were observed in 51 and 16 cats, respectively. Using therapeutic kinetic data, radiation doses to the thyroid gland were calculated retrospectively on the basis of 2 methods for determining the activity of /sup 131/I administered: (1) actual administration of tracer-compensated activity and (2) hypothetic administration of uniform activity (3 mCi). Because of the good predictive ability of tracer kinetic data for the therapeutic kinetic data, the tracer-compensated radiation doses came significantly (P = 0.008) closer to the therapeutic goal than did the uniform-activity doses. In addition, the use of tracer kinetic information reduced the extent of the tendency for consistently high uniform-activity doses. A manual method for acquiring tracer kinetic data was developed and was an acceptable alternative to computerized techniques. Adoption of this method gives individuals and institutions with limited finances the opportunity to characterize the iodine kinetics in cats before proceeding with administration of therapeutic activities of /sup 131/I.« less

Development of a Screening Approach to Detect Thyroid Disrupting Chemicals that Inhibit the Human Sodium/Iodide Symporter (NIS)

EPA Science Inventory

Thyroid hormone synthesis requires active iodide uptake mediated by the sodium/iodide symporter (NIS). Monovalent anions, such as the environmental contaminant perchlorate, have been well characterized as competitive inhibitors of NIS, yet limited information exists for more stru...

SPORADIC GOITROUS CRETINISM

PubMed Central

Mosier, H. David

1959-01-01

Five to 10 per cent of cretinism in the United States is due to some congenital enzymatic defect in thyroid hormone synthesis. The clinical signs of hypothyroidism appear in early infancy. Differentiation from athyreotic cretinism is important because the metabolic defect tends to be familial and its presence in the patient's infant relatives should be diagnosed as early as possible. The differentiation is easily made if a goiter is discernible, but if it is not, radioiodine uptake should be measured, for in this condition the uptake is normal or greater. Thyroid replacement is the treatment in either the athyreotic state or the metabolic deficiency. The three known defects in thyroid hormone synthesis are (1) failure to oxidize iodine to elemental iodine resulting in failure of all subsequent processes; (2) failure to deiodinate free iodotyrosine, and (3) failure to form iodothyronine although the previous steps are accomplished. PMID:13618742

Diffuse thyroid uptake incidentally found on 18F-fluorodeoxyglucose positron emission tomography in subjects without cancer history.

PubMed

Lee, Ji Young; Choi, Joon Young; Choi, Yoon-Ho; Hyun, Seung Hyup; Moon, Seung Hwan; Jang, Su Jin; Choe, Yearn Seong; Lee, Kyung-Han; Kim, Byung-Tae

2013-01-01

We investigated the clinical significance of incidental diffuse thyroid uptake (DTU) on (18)F-FDG PET in subjects without a history of cancer. This study included 2062 studies from adults who underwent (18)F-FDG PET as a cancer screening program. Subjects were divided into the following two groups: with (group I) or without (group II) DTU. The presence of DTU and the thyroid visual grading score were compared with thyroid function tests, serum anti-microsomal antibody (AMA) levels, and the presence of diffuse parenchymal change (DPC) on ultrasonography (USG). DTU was found in 6.6% of the scans (137/2062). Serum thyroid stimulating hormone (TSH) and AMA levels were significantly higher in group I than in group II. Increased AMA level (55.1%) and DPC (48.7%) were more frequently found in group I (p < 0.001). The proportion of subjects with any abnormal results in serum free thyroxine, triiodothyronine, TSH, or AMA levels or DPC on USG was significantly higher in group I than in group II (71.5% vs. 10.6%, p < 0.001), and was significantly and gradually increased according to the visual grading score group (0 vs. 1-2 vs. 3-4 = 10.6% vs. 58.5% vs. 90.9%, p < 0.001). TSH and is AMA levels were significantly increased according to the visual grading score. The presence or degree of incidental DTU on (18)F-FDG PET is closely correlated with increased serum AMA and TSH levels, and the presence of DPC on USG. Therefore, the most plausible pathological cause of DTU may be cell damage by an autoimmune mechanism.

Radiation Exposure to Relatives of Patients Treated with Iodine-131 for Thyroid Cancer at Siriraj Hospital.

PubMed

Tonnonchiang, Siriporn; Sritongkul, Nopamon; Chaudakshetrin, Pachee; Tuntawiroon, Malulee

2016-02-01

Thyroid cancer patients treated with 1-131 are potential source of radiation exposure to relatives who are knowingly and willingly exposed to ionizing radiation as a result of providing comfort to patients undergoing I-131 therapy. This study aims to determine radiation dose received by relatives who care for non self-supporting 1-131 patients at Siriraj Hospital. Twenty caregivers of 20 patients underwent I-131 therapy for thyroid cancer with a standard protocol were given specific instructions with regard to radiation safety and provided with electronic digital dosimeter to continuously measure radiation dose received on daily basis, three days in the hospital. On the day patient is released, thyroid uptake estimates were performed to assess internal radiation dose received by caregivers. The 3-day accumulative doses to caregivers to patients receiving 150 mCi (n = 11) and 200 mCi (n = 9) of I-131 ranged from 37 to 333 uSv and 176 to 1,920 pSv respectively depending on the level of supports required. Thyroid uptake estimates in all caregivers were undetectable. Dosimeter indicated a maximum whole-body dose of1.92 mSv was more than the public dose limit of] mSv but within the dose constraint of 5 mSv for caregivers. Radiation dose to caregivers of a non self-supporting hospitalized patient undergoing 1-131 therapy were well below the limits recommended by the ICRP. The patients can be comforted with confidence that dose to caregivers will be less than the limit. This study provides guidance for medical practitioners to obtain practical radiation safety concerns associated with hospitalized patients receiving I-131 therapy especially when patient needs assistance.

[Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma].

PubMed

Adamczewski, Zbigniew; Makarewicz, Jacek; Mikosiński, Sławomir; Knapska-Kucharska, Małgorzata; Gunerska-Szadkowska, Anna; Oszukowska, Lidia; Karwowska, Anzelmina; Lewiński, Andrzej

2006-01-01

The loss of iodine uptake by differentiated thyroid carcinoma (DTC) cells is a major therapeutic problem especially in patients with nonsurgical metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted to retain iodine uptake as a result of redifferentiation (influence by retinoic acid receptors present in DTC cells). Between 1999 and 2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were treated twice - 13 treatment cycles in total). Side effects in skin and mucous membranes were observed in all the patients, however, their intensity did not require termination of the therapy. Increase of iodine uptake was observed in 5 patients (45%). Decreased Tg concentration was observed in 9 patients. In that group, increased (131)I uptake was observed in 4 patients with distant metastases. All determinations of Tg concentrations were carried out under TSH stimulation. 13-cis-retinoic acid causes an increase of radioiodine uptake in around half of treated patients, however, the follow-up of these patients indicates that this increase does not result in either full remission or even stabilisation of neoplastic disease. The possibility should be considered to use cis-retinoic acid as an independent therapeutic approach in patients with radioiodine non-avid foci of thyroid carcinoma especially those showing high expression of RARb and RXRg receptors.

Comparison of 800 and 3700 MBq iodine-131 for the postoperative ablation of thyroid remnant in patients with low-risk differentiated thyroid cancer.

PubMed

Caglar, Meltem; Bozkurt, Fani M; Akca, Ceren Kapulu; Vargol, Sezen Elhan; Bayraktar, Miyase; Ugur, Omer; Karaağaoğlu, Ergun

2012-03-01

The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.

Semiquantitative analysis and characterization of physiological biodistribution of (68)Ga-DOTA-TATE PET/CT.

PubMed

Kunikowska, Jolanta; Królicki, Leszek; Pawlak, Dariusz; Zerizer, Imene; Mikołajczak, Renata

2012-11-01

The aim of this study was to describe the normal physiological distribution of (68)Ga-DOTA-TATE using the SUV to reflect the density of somatostatin receptors in various organ systems. A total of 250 patients (90 men and 160 women) were imaged on a Biograph 64 PET/CT TruePoint (Siemens Medical Solutions) 60 to 80 minutes after injection of 120 to 200 MBq (3.2-5.4 mCi) of (68)Ga-DOTA-TATE. Visual assessment was performed on all studies on the multimodality workstation, and sites of increased uptake were recorded. The SUVmax was also calculated for each organ demonstrating increased (68)Ga-DOTA-TATE uptake. Visual assessment of the (68)Ga-DOTA-TATE PET/CT studies revealed increased uptake in the pituitary, salivary, thyroid glands, liver, spleen, adrenals, kidneys and bone reflecting normal increased somatostatin receptor expression. These sites were confirmed to be disease free on clinical follow-up and on correlation with other imaging (CT/MRI/ultrasound). Using semiquantitative analysis, SUVmax values were the highest in the pituitary gland [11 (4.5)], spleen [18.9 (6.6)], adrenal [14.0 (5.6)], and kidneys [14.2 (3.6)]. In addition, increasing uptake in the uncinate process of pancreas was noted in 12% of patients with SUVmax of 9.2 (3.3). Moderate (68)Ga-DOTA-TATE uptake was also present in salivary gland [3.4 (1.8)], thyroid [2.9 (1.2)], and normal liver [6.5 (2.2)]. The bones generally showed low (68)Ga-DOTA-TATE uptake with an SUVmax of 1.0 (0.3). Knowledge of the normal (68)Ga-DOTA-TATE distribution is highly important for accurate interpretation of this novel imaging modality, which is increasingly being used in the imaging of neuroendocrine tumor.

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study

PubMed Central

Kilfoy, Briseis A.; Zhang, Yawei; Park, Yikyung; Holford, Theodore R.; Schatzkin, Arthur; Hollenbeck, Albert; Ward, Mary H.

2010-01-01

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk (RR) for the highest quintile versus lowest quintile RR=2.28, 95% CI: 1.29–4.04l; p-trend <0.001); however, we observed no trend with intake among women (p-trend=0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95%CI: 1.09–4.05; p-trend=0.05) and follicular thyroid cancer (RR= 3.42; 95%CI: 1.03–11.4; p-trend=0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR= 2.74; 95%CI: 0.86–8.77; p-trend=0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted. PMID:20824705

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study.

PubMed

Kilfoy, Briseis A; Zhang, Yawei; Park, Yikyung; Holford, Theodore R; Schatzkin, Arthur; Hollenbeck, Albert; Ward, Mary H

2011-07-01

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50-71 years in 1995-1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29-4.041; p-trend <0.001); however, we observed no trend with intake among women (p-trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09-4.05; p-trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03-11.4; p-trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86-8.77; p-trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted. Published 2010 UICC.

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

PubMed Central

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules. PMID:20847957

Prediction of thyroidal 131I effective half-life in patients with Graves' disease.

PubMed

Zhang, Ruiguo; Zhang, Guizhi; Wang, Renfei; Tan, Jian; He, Yajing; Meng, Zhaowei

2017-10-06

Calculation of effective thyroidal half-life (Teff) of iodine-131( 131 I) is cumbersome and tedious. The aim of this study was to investigate factors that could be used to predict Teff and to develop a Teff prediction model in Graves' disease patients. A total of 256 patients with GD were involved in this study. We investigated the influences of age, gender, disease duration, thyroid weight, antithyroid drugs, antithyroid drugs discontinuation period (ADP), thyroid function indexes, thyroid autoantibodies, thyroid-stimulating hormone receptor antibody (TRAb) level and radioactive iodine uptake (RAIU) values before 131 I therapy on Teff, applying univariate and multivariate analyses. Teff correlated negatively with thyroid peroxidase antibody, TRAb and thyroid weight, as well as positively with 24-hour, 48-hour, and 72-hour RAIU. Additionally, a longer ADP (especially≥ 14d) or without antithyroid drugs before 131 I therapy led to a longer Teff. Stepwise multiple linear regression analysis showed that 24-hour and 72-hour RAIU were statistically significant predictors of Teff ( P <0.001). The relationship was: predictive Teff=5.277+0.295×72-hour RAIU-0.217×24-hour RAIU (r =0.865, P < 0.001). The present results indicate that prediction of Teff from 24-hour and 72-hour RAIU is feasible in patients with Graves' disease, with high prediction accuracy.

Modulation of thyroidal radioiodide uptake by oncological pipeline inhibitors and Apigenin

PubMed Central

Lakshmanan, Aparna; Scarberry, Daniel; Green, Jill A.; Zhang, Xiaoli; Selmi-Ruby, Samia; Jhiang, Sissy M.

2015-01-01

Targeted radioiodine therapy for thyroid cancer is based on selective stimulation of Na+/I− Symporter (NIS)-mediated radioactive iodide uptake (RAIU) in thyroid cells by thyrotropin. Patients with advanced thyroid cancer do not benefit from radioiodine therapy due to reduced or absent NIS expression. To identify inhibitors that can be readily translated into clinical care, we examined oncological pipeline inhibitors targeting Akt, MEK, PI3K, Hsp90 or BRAF in their ability to increase RAIU in thyroid cells expressing BRAFV600E or RET/PTC3 oncogene. Our data showed that (1) PI3K inhibitor GDC-0941 outperformed other inhibitors in RAIU increase mainly by decreasing iodide efflux rate to a great extent; (2) RAIU increase by all inhibitors was extensively reduced by TGF-β, a cytokine secreted in the invasive fronts of thyroid cancers; (3) RAIU reduction by TGF-β was mainly mediated by NIS reduction and could be reversed by Apigenin, a plant-derived flavonoid; and (4) In the presence of TGF-β, GDC-0941 with Apigenin co-treatment had the highest RAIU level in both BRAFV600E expressing cells and RET/PTC3 expressing cells. Taken together, Apigenin may serve as a dietary supplement along with small molecule inhibitors to improve radioiodine therapeutic efficacy on invasive tumor margins thereby minimizing future metastatic events. PMID:26397139

Pharmacology of bovine and human thyrotropin: an historical perspective.

PubMed

Robbins, J

1999-05-01

Before the induction of a brief period of hypothyroidism became the standard method for inducing 131I uptake in thyroid cancer diagnosis and therapy, several other methods were explored and used. At the dawn of this new era of recombinant human thyrotropin (TSH) it is of interest to reflect briefly on some of this work. Partially purified bovine TSH (bTSH) was supplied for many years by the Armour Company as Thytropar for intramuscular injection and was first used in thyroid cancer 50 years ago at the Montefiore Hospital and at the Memorial Sloan Kettering Cancer Center in New York City. Most of the patients were already hypothyroid and bTSH induced further 131I uptake in only a few. Experience over the next 30 years revealed frequent allergic reactions, occasionally serious ones, and in 1961 it was shown that prolonged use could result in resistance to both bTSH and human TSH. bTSH was, therefore, reserved for thyroid cancer patients unable to increase endogenous TSH when hypothyroid. bTSH also was used widely as a test to distinguish between hypothyroidism caused by thyroid or pituitary failure until it was replaced by thyrotropin-releasing hormone (TRH). In a few studies, TRH was also tested as an adjuvant to increase endogenous TSH and thus help to stimulate function in thyroid cancer, but this attracted little interest. Prolonged hypothyroidism, enhanced by antithyroid drugs, was used early on, but this very effective stimulant of thyroid cancer function was, for multiple reasons, discarded. Beginning interest 15 to 25 years ago in obtaining TSH from human pituitary glands, a byproduct of growth hormone production, was interrupted when this product was found to risk development of Creutzfeld-Jakob disease. Recombinant human TSH, a safe and effective substitute, is now ready for widespread use and development in thyroid cancer management.

Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT.

PubMed

Thanseer, N T K; Bhadada, Sanjay Kumar; Sood, Ashwani; Parihar, Ashwin Singh; Dahiya, Divya; Singh, Priyanka; Basher, Rajender Kumar; Das, Ashim; Mittal, Bhagwant R

2018-04-01

18 F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of 18 F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented.

Diffuse thyroid 18F-FDG uptake after R-CHOP therapy predicts favorable outcome in patients with DLBCL.

PubMed

Song, Moo-Kon; Chung, Joo-Seop; Kim, Seong-Jang; Kim, Sang-Soo; Shin, Ho-Jin

2015-06-01

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0-21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

Project Overview: Inhibition of the Sodium-Iodide Symporter by Perchlorate: Evaluation of Lifestage Sensitivity Using PBPK Modeling

EPA Science Inventory

Perchlorate (ClO4-) competitively inhibits uptake of iodide by the sodium-iodide symporter (NIS) in laboratory animals and humans. NIS is found in many tissues, but is primarily responsible for sequestering iodide into the thyroid, enabling biosynthesis of thyroid hormones. The N...

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

Resveratrol has anti-thyroid effects both in vitro and in vivo.

PubMed

Giuliani, Cesidio; Iezzi, Manuela; Ciolli, Laura; Hysi, Alba; Bucci, Ines; Di Santo, Serena; Rossi, Cosmo; Zucchelli, Mirco; Napolitano, Giorgio

2017-09-01

Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 μM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thyroid Hormones and Thyroid Disease in Relation to Perchlorate Dose and Residence Near a Superfund Site

PubMed Central

Gold, Ellen B.; Blount, Benjamin C.; Rasor, Marianne O’Neill; Lee, Jennifer S.; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-01-01

Background Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. Objectives In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Methods Residential blocks were randomly selected from areas: 1) with potential perchlorate exposure via drinking water; 2) with potential exposure to environmental contaminants; and 3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20–50 years during 1988–1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone [TSH] and free thyroxine [fT4]) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Results Residential location and current perchlorate dose were not associated with thyroid function or disease. Conclusions No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped. PMID:22968349

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

Evaluation of the normal range of values for uptake of radioactive iodine by the thyroid gland.

PubMed Central

Schober, B.; Hunt, J. A.

1976-01-01

Uptake of radioactive iodine by the thyroid gland after oral administration of 75 muCi was determined in 1971-72 in 60 euthyroid female volunteers from the North Shore of Vancouver. Values were as low as 3% at 4 hours and 7% at 24 hours in subjects otherwise proven to be euthyroid. The highest values found were 13 and 26% at 4 and 24 hours. The effective thyroxine ratios were all within the accepted normal range. However, more than half of the volunteers showed some enlargement of the thyroid gland. These results suggest an increased iodine pool in the subjects, the likley source being iodine in mild, dairy products and erythrosine, a colouring agent in foods and pharmaceutical products. Potassium iodate, used sometimes in bread baking, contributed little to this pool in our sample. Subjects were, on the average, 9 to 25% heavier than their peers 20 years ago. PMID:1277057

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

PubMed

Horton, Megan K; Blount, Benjamin C; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-11-01

Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Co-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

PubMed Central

Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-01-01

Background Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy. Objectives We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (± 2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results Individual analyte concentrations in urine were significantly correlated (Spearman’s r 0.4–0.5, p < 0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. PMID:26408806

Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal.

PubMed

Vallejo Casas, Juan A; Mena Bares, Luisa M; Gálvez Moreno, Maria A; Moreno Ortega, Estefanía; Marlowe, Robert J; Maza Muret, Francisco R; Albalá González, María D

2016-06-01

Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.

Internal dosimetry of inhaled iodine-131.

PubMed

Kiani Nasab, Mitra; Rafat Motavalli, Laleh; Miri Hakimabad, Hashem

2018-01-01

In this paper, the dose assessment for the iodine inhalation exposure in 19 aerosol sizes and three gas/vapor forms at three levels of thyroid uptake, was performed. Two different modes of work (light vs. heavy) and breathing (nose vs. mouth) for aerosol inhalation were investigated. In order to calculate the cumulated activities per unit of inhaled activity, a combined model which included the latest models of both human respiratory and alimentary tract was developed. The S values for 131 I were computed based on the ICRP adult male and female reference voxel phantoms by the Monte Carlo method. Then, the committed equivalent and committed effective dose coefficients were obtained (The data are available at http://www.um.ac.ir/∼mirihakim). In general, for the nonzero thyroid uptakes, the maximum cumulated activity was found in the thyroid. When the thyroid is blocked, however, the maximum depends on the work and breathing mode and radioisotope form. Overall, the maximum CED coefficient was evaluated for the inhalation of elemental iodine at thyroid uptake of ∼27% (2.8 × 10 -8 Sv/Bq). As for the particle inhalation per se, mouth breathing of 0.6 nm and 0.2 μm AMTD particles showed to have the maximum (2.8 × 10 -8 Sv/Bq) and minimum (6.4 × 10 -9 Sv/Bq) CED coefficients, respectively. Compared to the reference CED coefficients, the authors found an increase of about 58% for inhalation of the aerosols with AMAD of 1 μm and 70% for 5 μm. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear imaging of iodine uptake in mouse tissues

NASA Astrophysics Data System (ADS)

Hammond, W. T.; Bradley, E. L.; Qian, J.; Majewski, S.

2005-04-01

We have designed and employed a compact gamma camera based on pixellated scintillators and position-sensitive photomultipliers to obtain in vivo images in mice of biological substances tagged with 125-I. Biomedical imaging studies make use of radioactive isotopes of iodine. In these applications, protection of the thyroid from the effects of the radioactive material can be important. We have studied in vivo the effectiveness in mice of pre-administration of KI in various concentrations to evaluate both the biologically effective doses for thyroid protection and the potential for use in general sodium iodide symporter studies. These findings have important implications for both intentional and accidental exposure to radioiodine.

Percutaneous ethanol injection of large autonomous hyperfunctioning thyroid nodules.

PubMed

Tarantino, L; Giorgio, A; Mariniello, N; de Stefano, G; Perrotta, A; Aloisio, V; Tamasi, S; Forestieri, M C; Esposito, F; Esposito, F; Finizia, L; Voza, A

2000-01-01

To verify the effectiveness of percutaneous ethanol injection (PEI) in the treatment of large (>30-mL) hyperfunctioning thyroid nodules. Twelve patients (eight women, four men; age range, 26-76 years) with a large hyperfunctioning thyroid nodule (volume range, 33-90 mL; mean, 46.08 mL) underwent PEI treatment under ultrasonographic (US) guidance. US was used to calculate the volume of the nodules and to assess the diffusion of the ethanol in the lesions during the procedure. When incomplete necrosis of the nodule was depicted at scintigraphy performed 3 months after treatment, additional PEI sessions were performed. Four to 11 PEI sessions (mean, seven) were performed in each patient, with an injection of 3-14 mL of 99.8% ethanol per session (total amount of ethanol per patient, 30-108 mL; mean, 48.5 mL). At scintigraphy after treatment in all patients, recovery of extranodular uptake, absence of uptake in the nodule, and normalization of thyroid-stimulating hormone (thyrotropin) levels were observed. In all patients, US showed volume reductions of 30%-50% after 3 months and 40%-80% after 6-9 months. Side effects were self-limiting in all patients. During the 6-48-month follow-up, no recurrence was observed. PEI is an effective and safe technique for the treatment of large hyperfunctioning thyroid nodules.

Effect of Dietary Intake of Stable Iodine on Dose-per-unit-intake Factors for 99Tc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strom, Daniel J.

It is well-known that the human thyroid concentrates iodine more than 100 times the concentration in plasma. Also well-known is the fact that large amounts of stable iodine in the diet can limit thyroid uptake of total iodine; this is the basis for administering potassium iodide following a release of radioiodine from a nuclear reactor accident or nuclear weapon detonation. Many researchers have shown enhanced concentrations of both organic and inorganic iodine in saliva and breast milk. Technetium-99 is a long-lived (231,000 year half-life) radionuclide of concern in the management of high-level radioactive waste. There is no doubt that 99Tc,more » if it is in groundwater, will be found in the chemical form of pertechnetate, 99TcO4?. Pertechnetate is a large anion, almost identical in size to iodide, I?. The nuclear medicine literature shows that pertechnetate concentrates in the thyroid, salivary glands, and lactating breast in addition to the stomach, liver, and alimentary tract as currently recognized by the International Commission on Radiological Protection (ICRP). The fact that large intakes of stable iodine (127I) in the diet limit uptake of iodine by the thyroid leads one to generalize that stable iodine in the diet may also limit thyroid uptake of pertechnetate. While there is at least one report that iodine in the diet blocks uptake of 99mTcO4? by the thyroid and salivary glands (which have the same Na/I symporter, the biochemical concentration mechanism), the level of protective effect seen for blocking radioactive iodine is not expected for 99TcO4? because pertechnetate does not become organically bound in the thyroid and thus is not retained for months the way iodide is. While it does account for Tc concentration in the thyroid, the existing ICRP biokinetic model for technetium does not take enhanced concentrations in salivary gland and breast tissue into account. From the survey of the nuclear medicine literature, it is not possible to compute the effect of stable iodine in the diet on the dose per unit intake factors for 99Tc without developing an improved biokinetic model for technetium. Specific experiments should be designed to quantitatively evaluate 99TcO4? metabolism, excretion, and secretion, as well as to evaluate its chemical toxicity It is recommended that the ICRP reexamine its biokinetics models for Tc based on nuclear medicine data that have accumulated over the years. In particular, the ICRP ignores the lactation pathway, the enhanced concentration of Tc in breast and breast milk, and enhanced concentration of Tc (and I) in the salivary glands as well as in the thyroid. The ICRP should also explicitly incorporate the effect of stable iodine in the diet into both its models for iodine and technetium. The effect of concentration of Tc in breast milk needs further study for dosimetric implications to nursing infants whose mothers may ingest 99TcO4? from groundwater sources. The ICRP should also investigate the possibility of enhanced concentration of both I and Tc in the non-lactating female breast. To do these re-evaluations of biokinetic models, new experiments designed specifically to evaluate these questions concerning the biokinetics of Tc and I are needed.« less

A Case of Painful Hashimoto Thyroiditis that Mimicked Subacute Thyroiditis

PubMed Central

Seo, Hye Mi; Kim, Miyeon; Bae, Jaeseok; Kim, Jo-Heon; Lee, Jeong Won; Lee, Sang Ah; Koh, Gwanpyo

2012-01-01

Hashimoto thyroiditis (HT) is an autoimmune thyroid disorder that usually presents as a diffuse, nontender goiter, whereas subacute thyroiditis (SAT) is an uncommon disease that is characterized by tender thyroid enlargement, transient thyrotoxicosis, and an elevated erythrocyte sedimentation rate (ESR). Very rarely, patients with HT can present with painful, tender goiter or fever, a mimic of SAT. We report a case of painful HT in a 68-year-old woman who presented with pain and tenderness in a chronic goiter. Her ESR was definitely elevated and her thyroid laboratory tests suggested subclinical hypothyroidism of autoimmune origin. 99mTc pertechnetate uptake was markedly decreased. Fine needle aspiration biopsy revealed reactive and polymorphous lymphoid cells and occasional epithelial cells with Hürthle cell changes. Her clinical symptoms showed a dramatic response to glucocorticoid treatment. She became hypothyroid finally and is now on levothyroxine therapy. PMID:22570820

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

PubMed

Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

2013-06-01

Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PubMed

Topić Vučenović, Valentina; Rajkovača, Zvezdana; Jelić, Dijana; Stanimirović, Dragi; Vuleta, Goran; Miljković, Branislava; Vučićević, Katarina

2018-05-13

Radioiodine ( 131 I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131 I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131 I kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131 I biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of 131 I into the thyroid (k tu ) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT 4 ), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131 I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k tu from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT 4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131 I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

PubMed

Demirci, Emre; Sahin, Onur Erdem; Ocak, Meltem; Akovali, Burak; Nematyazar, Jamal; Kabasakal, Levent

2016-11-01

Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Perchlorate in Water Supplies: Sources, Exposures, and Health Effects

PubMed Central

Steinmaus, Craig M.

2016-01-01

Perchlorate exposure occurs from ingestion of natural or manmade perchlorate in food or water. Perchlorate is used in a variety of industrial products including missile fuel, fireworks, and fertilizers, and industrial contamination of drinking water supplies has occurred in a number of areas. Perchlorate blocks iodide uptake into the thyroid, and decreases the production of thyroid hormone, a critical hormone for metabolism, neurodevelopment, and other physiologic functions. Occupational and clinical dosing studies have not identified clear adverse effects, but may be limited by small sample sizes, short study durations, and the inclusion of mostly healthy adults. Expanding evidence suggests that young children, pregnant women, fetuses, and people co-exposed to similarly acting agents may be especially susceptible to perchlorate. Given the ubiquitous nature of perchlorate exposure, and the importance of thyroid hormone for brain development, studying the impact of perchlorate on human health could have far-reaching public health implications. PMID:27026358

Clinical value of intraoperative neuromonitoring of the recurrent laryngeal nerves in improving outcomes of surgery for well-differentiated thyroid cancer.

PubMed

Barczyński, Marcin; Konturek, Aleksander; Stopa, Małgorzata; Hubalewska-Dydejczyk, Alicja; Richter, Piotr; Nowak, Wojciech

2011-04-01

The recurrent laryngeal nerve (RLN) is particularly prone to injury during thyroidectomy in case of extralaryngeal bifurcation being present in approximately one-third of patients near the inferior thyroid artery or ligament of Berry. Meticulous surgical dissection in this area may be additionally facilitated by the use of intraoperative neuromonitoring (IONM) to assure safe and complete removal of thyroid tissue. The aim of the study was to verify the hypothesis that meticulous surgical technique of tissue dissection in the area of the posterior surface of the thyroid capsule and adjacent RLN may be additionally facilitated by intraoperative neuromonitoring (IONM), and may contribute to increasing the safety and radicalness of total thyroidectomy in patients with well-differentiated thyroid cancer. The outcomes of total thyroidectomy with level VI lymph node clearance for well-differentiated thyroid cancer (WDTC; pT1-3, N0-1, Mx) were retrospectively compared between 151 patients undergoing surgery with IONM (01/2005-06/2009) and 151 patients undergoing surgery without IONM (2003-2004). RLN morbidity (calculated for nerves at risk) was assessed by videolaryngoscopy or indirect laryngoscopy (mandatory before and after surgery and at 12-month follow-up). The anatomical course of the extralaryngeal segment of RLNs were analyzed in detail in each operation. Thyroid iodine uptake (131I) was measured during endogenous TSH stimulation test a week before radioiodine therapy. Among patients operated with vs. without IONM, the early RLN injury rate was 3% vs. 6.7% (p=0.02), including 2% vs. 5% (p=0.04) of temporary nerve lesions, and 1% vs. 1.7% of permanent nerve events (p=0.31), respectively. Extralaryngeal RLN bifurcation was identified in 42 (27.8%) vs. 25 (16.6%) of patients operated with vs. without IONM, respectively (p=0.001). Mean I-131 uptake following total thyroidectomy with vs. without IONM was 0.67 ± 0.39% vs. 1.59 ± 0.69% (p<0.001). 131I uptake lower than 1% was found in 106 (70.2%) vs. 38 (25.2%) patients operated with vs. without IONM, respectively (p<0.001). Most patients with WDTC who undergo total thyroidectomy have a small amount of residual thyroid tissue. The use of IONM may improve the outcomes of surgery among these patients by both increasing the completeness of total thyroidectomy and significantly reducing the prevalence of temporary RLN injury. The possible mechanism of this improvement is the aid in dissection at the level of the Berry's ligament offered by IONM which enhances the surgeon's ability to identify a branched RLN, and allows for reduction of traction injury and neuropraxia of the anterior branch of bifid nerves.

The prevalence of thyroid cancer in patients with hyperthyroidism

PubMed Central

Kunjumohamed, Fathimabeebi P.; Al-Busaidi, Noor B.; Al-Musalhi, Hilal N.; Al-Shereiqi, Sulaiman Z.; Al-Salmi, Issa S.

2015-01-01

Objectives: To determine the prevalence of thyroid cancer in patients with hyperthyroidism. Methods: This is a retrospective observational study using the data of 71 Omani patients with a diagnosis of hyperthyroidism due to Grave’s disease, toxic multinodular goiter, and solitary toxic adenoma. These patients underwent thyroidectomy at the Royal Hospital (RH), Muscat, Oman, and were followed up at the National Diabetes and Endocrine Center (NDEC) between 2007 and 2013. The details were collected from the medical records of both the RH and the NDEC. Patients who underwent thyroidectomy for other reasons like non-toxic goiter and hypothyroidism with cancer were excluded from the study. Results: Thyroid cancer was identified in 32.8% (n=23) of patients with hyperthyroidism. Half of these patients 52.1% (n=12) had papillary micro-cancer (intra-thyroidal), and 3 patients with Grave’s disease (13%) had lymph nodes metastasis (loco-regional infiltration. The cancer preponderance was higher in young (n=21, 91.3%) and female patients (n=18, 73.9%). Most patients with thyroid cancer had abnormal ultrasound neck findings and thyroid scintigraphy (99 mTc uptake). Conclusion: Many patients with hyperthyroidism in Muscat, Oman, especially those with Grave’s disease, show malignancy, and hence a proper initial evaluation of these patients is required as part of long-term management. PMID:26108596

The prevalence of thyroid cancer in patients with hyperthyroidism.

PubMed

Kunjumohamed, Fathimabeebi P; Al-Busaidi, Noor B; Al-Musalhi, Hilal N; Al-Shereiqi, Sulaiman Z; Al-Salmi, Issa S

2015-07-01

To determine the prevalence of thyroid cancer in patients with hyperthyroidism. This is a retrospective observational study using the data of 71 Omani patients with a diagnosis of hyperthyroidism due to Grave's disease, toxic multinodular goiter, and solitary toxic adenoma. These patients underwent thyroidectomy at the Royal Hospital (RH), Muscat, Oman, and were followed up at the National Diabetes and Endocrine Center (NDEC) between 2007 and 2013. The details were collected from the medical records of both the RH and the NDEC. Patients who underwent thyroidectomy for other reasons like non-toxic goiter and hypothyroidism with cancer were excluded from the study. Thyroid cancer was identified in 32.8% (n=23) of patients with hyperthyroidism. Half of these patients 52.1% (n=12) had papillary micro-cancer (intra-thyroidal), and 3 patients with Grave's disease (13%) had lymph nodes metastasis (loco-regional infiltration. The cancer preponderance was higher in young (n=21, 91.3%) and female patients (n=18, 73.9%). Most patients with thyroid cancer had abnormal ultrasound neck findings and thyroid scintigraphy (99 mTc uptake). Many patients with hyperthyroidism in Muscat, Oman, especially those with Grave's disease, show malignancy, and hence a proper initial evaluation of these patients is required as part of long-term management.

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurementsmore » were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

2014-01-15

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurementsmore » were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, S.; Bellamy, M.; Hertel, N.; ...

2015-03-25

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewji, S.; Bellamy, M.; Hertel, N.

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Effects of Sample Handling and Analytical Procedures on Thyroid Hormone Concentrations in Pregnant Women's Plasma.

PubMed

Villanger, Gro Dehli; Learner, Emily; Longnecker, Matthew P; Ask, Helga; Aase, Heidi; Zoeller, R Thomas; Knudsen, Gun P; Reichborn-Kjennerud, Ted; Zeiner, Pål; Engel, Stephanie M

2017-05-01

Maternal thyroid function is a critical mediator of fetal brain development. Pregnancy-related physiologic changes and handling conditions of blood samples may influence thyroid hormone biomarkers. We investigated the reliability of thyroid hormone biomarkers in plasma of pregnant women under various handling conditions. We enrolled 17 pregnant women; collected serum and plasma were immediately frozen. Additional plasma aliquots were subjected to different handling conditions before the analysis of thyroid biomarkers: storage at room temperature for 24 or 48 hours before freezing and an extra freeze-thaw cycle. We estimated free thyroid hormone indices in plasma based on T3 uptake. High correlations between plasma and serum (>0.94) and intraclass correlation coefficients for plasma handling conditions (0.96 to 1.00) indicated excellent reliability for all thyroid hormone biomarkers. Delayed freezing and freeze-thaw cycles did not affect reliability of biomarkers of thyroid function in plasma during pregnancy. See video abstract at, http://links.lww.com/EDE/B180.

Influence of lake trophic structure on iodine-131 accumulation and subsequent cumulative radiation dose to trout thyroids.

PubMed

Martinez, Nicole E; Johnson, Thomas E; Pinder, John E

2014-05-01

Iodine-131 is a major component of the atmospheric releases following reactor accidents, and the passage of (131)I through food chains from grass to human thyroids has been extensively studied. By comparison, the fate and effects of (131)I deposition onto lakes and other aquatic systems have been less studied. In this study we: (1) reanalyze 1960s data from experimental releases of (131)I into two small lakes; (2) compare the effects of differences in lake trophic structures on the accumulation of (131)I by fish; (3) relate concentrations in fish and fish tissues to that in the water column using empirically estimated uptake (L kg(-1) d(-1)) and loss (d(-1)) parameters; and (4) show that the largest concentrations in the thyroids of trout (Oncorhynchus mykiss) may occur from 8 to 32 days after initial release. Iodine-131 concentration in trout thyroids at 30-days post release may be >1000 times that in the water. Estimates of cumulative radiation dose (mGy) to thyroids computed using an anatomically-appropriate model of trout thyroid structure within the Monte Carlo N-particle modeling software predicted cumulative thyroid doses that increased approximately linearly after the first 8 days and resulted in 32-day cumulative thyroid doses that ranged from 6 mGy g(-1) to 18 mGy g(-1) per 1 Bq mL(-1) of initial (131)I in the water depending upon fish size. The majority of this dose is due to beta emissions, and the dose varies with positions in the thyroid tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expression and Function of Thyroid Hormone Transporters in the Microvillous Plasma Membrane of Human Term Placental Syncytiotrophoblast

PubMed Central

Loubière, L. S.; Vasilopoulou, E.; Glazier, J. D.; Taylor, P. M.; Franklyn, J. A.; Kilby, M. D.

2012-01-01

The transplacental passage of thyroid hormones (THs) from mother to fetus in humans has been deduced from observational clinical studies and is important for normal fetoplacental development. To investigate the transporters that regulate TH uptake by syncytiotrophoblast (the primary barrier to maternal-fetal exchange, which lies in direct contact with maternal blood), we isolated the microvillous plasma membrane (MVM) of human term syncytiotrophoblasts. We have demonstrated that MVM vesicles express plasma membrane TH transporter proteins, including system-L (L-type amino acid transporter 1 and CD98), monocarboxylate transporters (MCTs) 8 and 10, organic anion-transporting polypeptides 1A2 and 4A1. We provide the first definitive evidence that the human syncytiotrophoblast MVM is capable of rapid, saturable T4 and T3 uptake at similar rates and in a Na+-independent manner. These two major forms of THs could not significantly inhibit each others' uptake, suggesting that each is mediated by largely different transporters. No single transporter was noted to play a dominant role in either T4 or T3 uptake. Using combinations of transporter inhibitors that had an additive effect on TH uptake, we provide evidence that 67% of saturable T4 uptake is facilitated by system-L and MCT10 with a minor role played by organic anion-transporting polypeptides, whereas 87% of saturable T3 uptake is mediated by MCT8 and MCT10. Our data demonstrate that syncytiotrophoblast may control the quantity and forms of THs taken up by the human placenta. Thus, syncytiotrophoblast could be critical in regulating transplacental TH supply from the mother to the fetus. PMID:23087173

Thyroiditis: an integrated approach.

PubMed

Sweeney, Lori B; Stewart, Christopher; Gaitonde, David Y

2014-09-15

Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

PubMed Central

Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

2015-01-01

Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

Transient neonatal hypothyroidism due to transplacental transfer of maternal immunoglobulins that inhibit TSH binding, TSH-induced cAMP increase and cell growth.

PubMed

Cho, B Y; Shong, Y K; Lee, H K; Koh, C S; Min, H K; Lee, M

1988-12-01

Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr-old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH-stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H-thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby.

Radioiodine remnant ablation in differentiated thyroid cancer after combined endogenous and exogenous TSH stimulation.

PubMed

Vrachimis, A; Schober, O; Riemann, B

2012-01-01

Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed. The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation. Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III. The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ENHANCES ALTERATIONS OF THE PITUITARY-THYROID AXIS CAUSED BY THE INDIVIDUAL CHEMICALS IN ADULT MALE F344 RATS

EPA Science Inventory

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the U.S. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting the iodide uptake, thus hindering the synt...

Submandibular Lateral Ectopic Thyroid Tissue: Ultrasonography, Computed Tomography, and Scintigraphic Findings

PubMed Central

Çeliker, Metin; Beyazal Çeliker, Fatma; Turan, Arzu; Beyazal, Mehmet; Beyazal Polat, Hatice

2015-01-01

Ectopic thyroid can be encountered anywhere between the base of tongue and pretracheal region. The most common form is euthyroid neck mass. Herein, we aimed to present the findings of a female case with ectopic thyroid tissue localized in the left submandibular region. A 44-year-old female patient, who underwent bilateral subtotal thyroidectomy four years ago with the diagnosis of multinodular goiter, was admitted to our hospital due to a mass localized in the left submandibular area that gradually increased in the last six months. Neck ultrasonography, contrast-enhanced computed tomography, and scintigraphic examination were performed on the patient. On thyroid scintigraphy with Tc-99m pertechnetate, thyroid tissue activity uptake showing massive radioactivity was observed in the normal localization of the thyroid gland and in the submandibular localization. The focus in the submandibular region was excised. Pathological examination of the specimen showed normal thyroid follicle cells with no signs of malignancy. The submandibular mass is a rarely encountered lateral ectopic thyroid tissue. Accordingly, ectopic thyroid tissue should also be considered in the differential diagnosis of masses in the submandibular region. PMID:26634164

Use of thyroid scintigraphy and pituitary immunohistochemistry in the diagnosis of spontaneous hypothyroidism in a mature cat.

PubMed

Blois, Shauna L; Abrams-Ogg, Anthony C G; Mitchell, Colleen; Yu, Anthony; Stoewen, Debbie; Lillie, Brandon N; Kiupel, Matti

2010-02-01

A 12-year old, castrated male domestic shorthair cat presented with a 2-year history of poor hair coat, seborrhea, generalized pruritus and otitis externa. Low circulating concentrations of total serum thyroxine (TT(4)) and free thyroxine (fT(4)) and an elevated thyroid stimulating hormone concentration supported a diagnosis of primary hypothyroidism. Thyroid scintigraphy did not show uptake of radioactive technetium in the thyroid area. Treatment with levothyroxine resulted in clinical improvement. Recurrence of dermatitis 8 months after onset of treatment resulted in euthanasia of the cat. On post-mortem examination, thyroid tissue was not identified on gross or histological examination. Pituitary immunohistochemistry identified hyperplasia of chromophobe cells. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Effect of lithosperm on thyroidal /sup 32/P uptake at various times of injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breneman, W.R.; Zeller, F.J.

These experiments were performed to increase our understanding of possible side effects in the use of extracts of the plant Lithospermum ruderale (LSPM) as a contraceptive. Cold-water extracts of LSPM were used to note possible effects on injected TSH and on endogenous TSH which was increased by the use of propylthiouracil. It was demonstrated that LSPM had a biphasic effect on both endogenous and exogenous TSH activity as measured by chick thyroid /sup 32/P uptake. When given 18h before autopsy, LSPM decreased TSH activity in both, whereas when LSPM was administered 42h or 44h before autopsy, TSH activity was significantlymore » increased.« less

Hyperfunctioning thyroid cancer: a five-year follow-up.

PubMed

Azevedo, Monalisa Ferreira; Casulari, Luiz Augusto

2010-02-01

Differentiated thyroid cancer rarely occurs in association with hyperfunctioning nodules. We describe a case of a 47-year-old woman who developed symptoms of hyperthyroidism associated with a palpable thyroid nodule. Thyroid scintigraphy showed an autonomous nodule, and fine-needle aspiration biopsy was suggestive of papillary carcinoma. Laboratorial findings were consistent with the diagnosis of hyperthyroidism. The patient underwent thyroidectomy and a papillary carcinoma of 3.0 x 3.0 x 2.0 cm, follicular variant, was described by histological examination. The surrounding thyroid tissue was normal. Postoperatively, the patient received 100 mCi of (131)I, and whole body scans detected only residual uptake. No evidence of metastasis was detected during five years of follow-up. Hot thyroid nodules rarely harbor malignancies, and this case illustrated that, when a carcinoma occurs the prognosis seems to be very good with no evidence of metastatic dissemination during a long-term follow-up.

Spectrometric measurements of radioisotope activity in the thyroid

NASA Astrophysics Data System (ADS)

Osko, Jakub; Golnik, Natalia

2008-01-01

The results of measurements of iodine 131I and technetium 99mTc uptake in human thyroid, performed with scintillation or semiconductor detectors can exhibit a considerable uncertainty due to the differences in the thyroid position in the patient's neck. Basic physical laws of radiation attenuation and scattering show that the final shape of the registered spectrum should depends on the thyroid position in the neck and on the thickness of the tissue between the thyroid and the detector. The use of the spectrometric measuring method is proposed in this work for determination of the iodine gathering effective depth. The performed studies showed that the measurements results can be used for improving the accuracy of the iodine 131I activity in thyroid measurements and for selection of the group of patients for whom the anatomical position of the thyroid or the spatial distribution of the iodine gathering is much different than the standard one, assumed during the calibration of the counters. The results of the measurements were in agreement with Monte-Carlo calculations of the detector response. The method was used in routine monitoring of occupationally exposed persons, using the thyroid counter. A group of six persons with measurable internal contamination was selected and the measurements were performed on consecutive days, so the results could be registered at decreasing iodine activities in the thyroid. Larger series of measurements were performed at Brodno Regional Hospital in Warsaw, for a group of 95 patients after diagnostic administration of iodine 131I.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

PubMed

Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

2015-12-01

Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

MEK Inhibition Leads To Lysosome-Mediated Na+/I- Symporter Protein Degradation In Human Breast Cancer Cells

PubMed Central

Zhang, Zhaoxia; Beyer, Sasha; Jhiang, Sissy M

2013-01-01

The Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates active iodide uptake into thyroid follicular cells. NIS-mediated iodide uptake in thyroid cells is the basis for targeted radionuclide imaging and treatment of differentiated thyroid carcinomas and their metastases. Furthermore, NIS is expressed in many human breast tumors but not in normal non-lactating breast tissue, suggesting that NIS-mediated radionuclide uptake may also allow the imaging and targeted therapy of breast cancer. However, functional cell surface NIS expression is often low in breast cancer, making it important to uncover signaling pathways that modulate NIS expression at multiple levels, from gene transcription to post-translational processing and cell surface trafficking. In this study, we investigated NIS regulation in breast cancer by MEK (MAPK/ERK kinase) signaling, an important cell signaling pathway involved in oncogenic transformation. We found that MEK inhibition decreased NIS protein levels in all-trans retinoic acid (tRA)/hydrocortisone treated MCF-7 cells as well as human breast cancer cells expressing exogenous NIS. The decrease in NIS protein levels by MEK inhibition was not accompanied by a decrease in NIS mRNA or a decrease in NIS mRNA export from the nucleus to the cytoplasm. NIS protein degradation upon MEK inhibition was prevented by lysosome inhibitors, but not by proteasome inhibitors. Interestingly, NIS protein level was correlated with MEK/ERK activation in human breast tumors from a tissue microarray. Taken together, MEK activation appears to play an important role in maintaining NIS protein stability in human breast cancers. PMID:23404856

The Purity of Radioiodide-I131 Assessed by in Vivo and in Vitro Methods

PubMed Central

Fawcett, D. M.; Olde, G. L.; McLeod, L. E.

1962-01-01

Between 41 and 94% of the radioactivity of 24 preparations of I131 supplied without cysteine preservative was non-iodide on chromatographic analysis. Extraneous radio-activity was essentially absent from I131 supplied with cysteine. It was converted to iodide-I131 by 10-3 M cysteine or iodide but not by incubation at pH 2. The average thyroid uptake of I131 containing extraneous radioactivity was significantly lower than the uptake of I131 free from non-iodide impurity in 16 human subjects measured under controlled conditions and in a random group of 669 patients. Incubation of samples of I131 containing non-iodide radioactivity with tyrosine and cupric chloride resulted in the non-enzymatic formation of monoiodotyrosine-I131 either in the presence or absence of thyroid homogenate. Enzymatic formation of monoiodotyrosine-I131 by thyroid homogenates could be demonstrated only when I131 free from extraneous activity was used. ImagesFig. 1Fig. 2 PMID:13891874

A new appraisal of iodine refractory thyroid cancer.

PubMed

Vaisman, Fernanda; Carvalho, Denise P; Vaisman, Mario

2015-12-01

Thyroid cancer incidence is increasing all over the world - mostly due to an increase in the detection of small tumors that were previously undetected. A small percentage of these tumors lose the ability to uptake and/or to respond to radioiodine (RAI) therapy, especially in metastatic patients. There are several new therapeutic options that have emerged in the last 5 years to treat RAI refractory thyroid cancer patients, however, it is very important to properly identify RAI refractory patients and to clarify those appropriate for these treatments. In this review, we discuss the RAI refractory definitions and the criteria that have been suggested based on RAI uptake in the post therapy scan, as well as the response after RAI therapy and the possible molecular mechanisms involved in this process. We offer a review of the therapeutic options available at the moment and the therapeutic considerations based on a patient's individualized personal characteristics, primary tumor histology, tumor burden and location and velocity of lesion growth. © 2015 Society for Endocrinology.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

PubMed

Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

2014-08-01

Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lithium carbonate pre-treatment in 131-I therapy of hyperthyroidism.

PubMed

Płazińska, Maria Teresa; Królicki, Leszek; Bąk, Marianna

2011-01-01

The aim of the present work was to investigate the influence of lithium carbonate on the kinetics of radioiodine in the thyroid gland, and the long-lasting effect of radioiodine therapy pre-treated with lithium carbonate in patients with different types of hyperthyreosis and low baseline 24-h thyroidal radioactive iodine uptake (RAIU). The examinations were performed in two groups of patients: in a control group with RAIU 〉 30% and in patients with RAIU 〈 30%. All groups were comparable with regard to age, sex, duration and type of disease (Graves' disease, autonomous node, multinodular goitre). The control group was treated (without lithium) according to described protocol. The second group was pre-treated with lithium carbonate in a dose of 1.0 g/day for 6 days before radioiodine and 3 days thereafter. A significant increase in iodide uptake in the thyroid gland was observed during intake of lithium carbonate in 106 out of 128 patients. A decrease of T(3), FT(3), T(4), and FT(4) levels and no significant changes in concentration of TSH were observed as an effect of lithium carbonate treatment. Three years of follow-up show that the results of radioiodine therapy with short lasting lithium carbonate intake are better in the first year and are similar in the second and third years in comparison to the control group. Lithium pre-treatment in hyperthyroid patients with low baseline uptake of radioiodine can increase iodine retention in the thyroid gland independently of the primary disease and permits the use of lower doses of radiation in the therapy.

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

PubMed Central

Ravera, Silvia; Reyna-Neyra, Andrea; Ferrandino, Giuseppe; Amzel, L. Mario; Carrasco, Nancy

2017-01-01

Active iodide (I−) transport in both the thyroid and some extrathyroidal tissues is mediated by the N a+/I− symporter (NIS). In the thyroid, NIS-mediated I− uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. The molecular characterization of NIS in 1996 and the use of radioactive I− isotopes have led to significan advances in the diagnosis and treatment of thyroid cancer and provide the molecular basis for studies aimed at extending the use of radioiodide treatment in extrathyroidal malignancies. This review focuses on the most recent finding on I− homeostasis and I− transport deficiency-causin NIS mutations, as well as current knowledge of the structure/function properties of NIS and NIS regulatory mechanisms. We also discuss employing NIS as a reporter gene using viral vectors and stem cells in imaging, diagnostic, and therapeutic procedures. PMID:28192058

Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

PubMed

Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

2017-01-01

In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine.

PubMed

Moncayo, Roy; Moncayo, Helga

2017-06-01

Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy. Current biochemical evidence about the elements required to maintain thyroid function shows that these not only include dietary iodine but also magnesium, iron, selenium and coenzyme Q10. Iron is important for the synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process of iodine uptake; iodine has to be sufficiently present in the diet; selenium acts through selenoproteins to protect the thyroid cell during hormone synthesis and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As a consequence, good clinical practice requires additional biochemical information on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status. Since these elements are also important for the maintenance of reproductive function, we postulate that they constitute the connecting link between both endocrine systems.

Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

PubMed

Peterson, Mark E

2014-11-01

Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.

The rs2910164 Genetic Variant of miR-146a-3p Is Associated with Increased Overall Mortality in Patients with Follicular Variant Papillary Thyroid Carcinoma

PubMed Central

Kubiak, Anna; Czetwertyńska, Małgorzata; Świerniak, Michał; Gierlikowski, Wojciech; Kolanowska, Monika; Bakuła-Zalewska, Elwira; Jhiang, Sissy M.; Jażdżewski, Krystian; Wójcicka, Anna

2018-01-01

Aberrant expression of the sodium-iodide symporter (NIS) and the resistance to post-operative radioactive iodide treatment is a crucial cause of higher mortality of some thyroid cancer patients. In this study, we analyzed the impact of miR-146a on the expression and function of NIS and on the overall survival of thyroid cancer patients. The study included 2441 patients (2163 women; 278 men); including 359 cases with follicular variant of papillary thyroid carcinoma (fvPTC). miR:NIS interactions were analyzed in cell lines using in vivo binding and inhibition assays and radioactive iodine uptake assays. Tumor/blood DNA was used for rs2910164 genotyping. Overall survival was assessed retrospectively. In the results, we showed that miR-146a-3p directly binds to and inhibits NIS. Inhibition of miR-146a-3p restores the expression and function of NIS, increasing radioactive iodine uptake. Rs2910164 functional variant within miR-146a-3p is associated with increased overall mortality among fvPTC female patients. The deaths per 1000 person-years were 29.7 in CC carriers vs. 5.08 in GG/GC-carriers (HR = 6.21, p = 0.006). Higher mortality of CC vs. GG/GC carriers was also observed in patients with lower clinical stage (HR = 22.72, p < 0.001), smaller tumor size (pT1/pT2) (HR = 25.05, p < 0.001), lack of extrathyroidal invasion (HR = 9.03, p = 0.02), lack of nodular invasion (HR = 7.84, p = 0.002), lack of metastases (HR = 6.5, p = 0.005) and older (age at diagnosis >50 years) (HR = 7.8, p = 0.002). MiR-146a-3p underwent somatic mutations in 16.1% of analyzed specimens, mainly towards the deleterious C allele. In this report we propose a novel molecular marker of the clinical outcome of fvPTC patients. Rs2910164 increases the overall mortality with inhibition of NIS and disruption of radioiodine uptake as a possible mechanism. PMID:29495389

Comparison between computed tomography and (99m)TC- pertechnetate scintigraphy characteristics of the thyroid gland in cats with hyperthyroidism.

PubMed

Lautenschlaeger, Ines E; Hartmann, Antje; Sicken, Julia; Mohrs, Sabrina; Scholz, Volkher B; Neiger, Reto; Kramer, Martin

2013-01-01

Scintigraphy is currently the reference standard for diagnosing feline hyperthyroidism; however, computed tomography (CT) is more widely available in veterinary practice. The purposes of this prospective study were to describe the CT appearance of thyroid glands in cats with hyperthyroidism and compare CT findings with findings from (99m) Tc-pertechnetate scintigraphy. Twenty-five adult hyperthyroid cats were included. Plain CT images were acquired for each cat and the following characteristics recorded for each thyroid lobe: visibility, delineation, position, attenuation, shape, and subjective size. Scintigraphic images were also acquired and the following characteristics recorded: radiopharmaceutical uptake, delineation, ectopic foci, shape, and subjective size. In CT images, thyroid lobes were most commonly found between the second and fourth cervical vertebrae, dorsolateral to the trachea. Affected thyroid lobes (based on scintigraphy reference standard) were most commonly oval and moderately enlarged in CT images. A heterogeneous attenuation pattern (isoattenuating to adjacent soft tissues with hypo- and hyperattenuating foci) was most commonly found in affected thyroid lobes. A positive correlation (P < 0.01) was identified between CT and scintigraphy for left-to-right thyroid lobe size relationship and subjective size of the larger thyroid lobe. The CT estimated mass was significantly higher (median = 148.8; range = [0;357.6]) for the more active thyroid lobe compared to the less active thyroid lobe (median = 84.6; range = [0;312.3]); (W = 154; P < 0.01). Findings indicated that CT may not reliably differentiate unilateral vs. bilateral hyperthyroidism in cats; however, CT may be a reliable alternative test for correctly identifying the more active thyroid lobe. © 2013 Veterinary Radiology & Ultrasound.

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression of Duox1 and the Anion Transporter Pendrin

PubMed Central

Achouri, Younes; Hahn, Stephan; Many, Marie-Christine; Craps, Julie; Refetoff, Samuel; Liao, Xiao-Hui; Dumont, Jacques E.; Van Sande, Jacqueline; Corvilain, Bernard; Miot, Françoise; De Deken, Xavier

2016-01-01

Background: The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. Methods: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. Results: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. Conclusions: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype. PMID:27599561

Late manifestation of subclinical hyperthyroidism after goitrogenesis in an index patient with a N670S TSH receptor germline mutation masquerading as TSH receptor antibody negative Graves' disease.

PubMed

Schaarschmidt, J; Paschke, S; Özerden, M; Jäschke, H; Huth, S; Eszlinger, M; Meller, J; Paschke, R

2012-12-01

In 27 families with familial non-autoimmune hyperthyroidism (FNAH) reported up to date, the onset of hyperthyroidism varies from 18 months to 60 years. Also the manifestation of goitres is variable in these families. A 74-year-old woman first presented at the age of 69 years with tachyarrhythmia and hypertension. After initial treatment of her hypertension and oral anticoagulation for her intermittent atrial fibrillation, a thyroid workup revealed a suppressed TSH and normal fT3 and fT4. TPO, TSH receptor (TSHR), and thyroglobulin antibodies were negative. Thyroid ultrasound revealed a thyroid volume of 102 ml with several nodules with diameters of up to 2.6 cm right and up to 1.8 cm left. Scintigraphy showed a homogeneous Technetium-99 m ((99 m)Tc) uptake of 1.27%. She was subsequently treated with 1 GBq radioiodine ((131)I). At the age of 74, her thyroid function was normal and her thyroid volume decreased to 90 ml. Because of the diffuse (99 m)Tc uptake and the negative TPO, TSHR, and thyroglobulin antibodies, genetic analysis of her TSHR gene was performed, in spite of her negative family history for hyperthyroidism. Sequencing revealed a N670S TSHR germline mutation. Previous in vitro characterisation of this TSHR mutation suggests a weak constitutive activity, yet the experimental data are ambiguous. This case illustrates the necessity to analyse patients with hyperthyroidism accompanied by diffuse (99 m)Tc uptake and negative TPO, TSHR, and thyroglobulin antibodies for TSHR germline mutations. Moreover, it demonstrates that TSHR germline mutations may first lead to longstanding nodular goitrogenesis before the late manifestation of subclinical hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horton, Megan K., E-mail: megan.horton@mssm.edu; Blount, Benjamin C.; Valentin-Blasini, Liza

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New Yorkmore » City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.« less

Hiatal hernia uptake of iodine-131 mimicking mediastinal metastasis of papillary thyroid carcinoma.

PubMed

Haghighatafshar, Mahdi; Khajehrahimi, Farnaz

2015-01-01

There are a few case reports of hiatal hernia demonstrating thoracic uptake on I-131 scintigraphy. In this case, high thyroglobulin levels in combination with misinterpretation of I-131 uptake in the mediastinum, leaded to mismanagement of the patient. Here we present a case of focal I-131 uptake within a hiatal hernia initially mimicking an isolated mediastinal metastasis. There are many potential causes of false-positive I-131 scan result. In this case, adjunctive chest computed tomography and gastroesophageal barium study helped to elucidate the true nature of this I-131 uptake. False-positive findings may be caused by a wide variety of nonthyroidal carcinomas, which can concentrate radioiodine or from skin contamination. Several organs, such as the gastric, salivary glands, renal cyst, pericardial effusion, and ovarian can accumulate I-131. It should be borne in mind as a potential source of false-positive whole-body I-131 imaging.

Nitrate intake and the risk of thyroid cancer and thyroid disease.

PubMed

Ward, Mary H; Kilfoy, Briseis A; Weyer, Peter J; Anderson, Kristin E; Folsom, Aaron R; Cerhan, James R

2010-05-01

Nitrate is a contaminant of drinking water in agricultural areas and is found at high levels in some vegetables. Nitrate competes with uptake of iodide by the thyroid, thus potentially affecting thyroid function. We investigated the association of nitrate intake from public water supplies and diet with the risk of thyroid cancer and self-reported hypothyroidism and hyperthyroidism in a cohort of 21,977 older women in Iowa who were enrolled in 1986 and who had used the same water supply for >10 years. We estimated nitrate ingestion from drinking water using a public database of nitrate measurements (1955-1988). Dietary nitrate intake was estimated using a food frequency questionnaire and levels from the published literature. Cancer incidence was determined through 2004. We found an increased risk of thyroid cancer with higher average nitrate levels in public water supplies and with longer consumption of water exceeding 5 mg/L nitrate-N (for >or=5 years at >5 mg/L, relative risk [RR] = 2.6 [95% confidence interval (CI) = 1.1-6.2]). We observed no association with prevalence of hypothyroidism or hyperthyroidism. Increasing intake of dietary nitrate was associated with an increased risk of thyroid cancer (highest vs. lowest quartile, RR = 2.9 [1.0-8.1]; P for trend = 0.046) and with the prevalence of hypothyroidism (odds ratio = 1.2 [95% CI = 1.1-1.4]), but not hyperthyroidism. Nitrate may play a role in the etiology of thyroid cancer and warrants further study.

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

PubMed Central

Saito, T; Endo, T; Kawaguchi, A; Ikeda, M; Katoh, R; Kawaoi, A; Muramatsu, A; Onaya, T

1998-01-01

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue. PMID:9525971

Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism

PubMed Central

Bunch, Ronald; Leung, Angela M.

2016-01-01

Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40–69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health. PMID:26946249

Medical imaging by fluorescent x-ray CT: its preliminary clinical evaluation

NASA Astrophysics Data System (ADS)

Takeda, Tohoru; Zeniya, Tsutomu; Wu, Jin; Yu, Quanwen; Lwin, Thet T.; Tsuchiya, Yoshinori; Rao, Donepudi V.; Yuasa, Tetsuya; Yashiro, Toru; Dilmanian, F. Avraham; Itai, Yuji; Akatsuka, Takao

2002-01-01

Fluorescent x-ray CT (FXCT) with synchrotron radiation (SR) is being developed to detect the very low concentration of specific elements. The endogenous iodine of the human thyroid and the non-radioactive iodine labeled BMIPP in myocardium were imaged by FXCT. FXCT system consists of a silicon (111) double crystal monochromator, an x-ray slit, a scanning table for object positioning, a fluorescent x-ray detector, and a transmission x-ray detector. Monochromatic x-ray with 37 keV energy was collimated into a pencil beam (from 1 mm to 0.025 mm). FXCT clearly imaged endogenous iodine of thyroid and iodine labeled BMIPP in myocardium, whereas transmission x-ray CT could not demonstrate iodine. The distribution of iodine was heterogeneous within thyroid cancer, and its concentration was lower than that of normal thyroid. Distribution of BMIPP in normal rat myocardium was almost homogeneous; however, reduced uptake was slightly shown in ischemic region. FXCT is a highly sensitive imaging modality to detect very low concentration of specific element and will be applied to reveal endogenous iodine distribution in thyroid and to use tracer study with various kinds of labeled material.

Thyroid profiles in a patient with resistance to thyroid hormone and episodes of thyrotoxicosis, including repeated painless thyroiditis.

PubMed

Taniyama, Matsuo; Otsuka, Fumiko; Tozaki, Teruaki; Ban, Yoshiyuki

2013-07-01

Thyrotoxic disease can be difficult to recognize in patients with resistance to thyroid hormone (RTH) because the clinical symptoms of thyrotoxicosis cannot be observed, and thyrotropin (TSH) may not be suppressed because of hormone resistance. Painless thyroiditis is a relatively common cause of thyrotoxicosis, but its occurrence in RTH has not been reported. We assessed the thyroid profile in a patient with RTH and episodes of thyrotoxicosis who experienced repeated painless thyroiditis. A 44-year-old Japanese woman with RTH, which was confirmed by the presence of a P453A mutation in the thyroid hormone receptor β (TRβ) gene, showed a slight elevation of the basal levels of thyroid hormones, which indicated that her pituitary RTH was mild. She experienced a slight exacerbation of hyperthyroxinemia concomitant with TSH suppression. A diagnosis of painless thyroiditis was made because of the absence of TSH receptor antibodies, low Tc-99m pertechnetate uptake by the thyroid gland, and transient suppression followed by a slight elevation of TSH following the elevation of thyroid hormones. The patient's complaints of general malaise and occasional palpitations did not change throughout the course of painless thyroiditis. Three years later, painless thyroiditis occurred again without any deterioration of the clinical manifestations. Mild pituitary RTH can be overcome by slight exacerbation of hyperthyroxinemia during mild thyrotoxicosis. When pituitary resistance is severe and TSH is not suppressed, thyrotoxicosis may be overlooked.

High Level of Agreement Between Pretherapeutic 124I PET and Intratherapeutic 131I Imaging in Detecting Iodine-Positive Thyroid Cancer Metastases.

PubMed

Ruhlmann, Marcus; Jentzen, Walter; Ruhlmann, Verena; Pettinato, Cinzia; Rossi, Gloria; Binse, Ina; Bockisch, Andreas; Rosenbaum-Krumme, Sandra

2016-09-01

The aim of this retrospective study was to assess the level of agreement between PET and scintigraphy using diagnostic amounts of (124)I and therapeutic amounts of (131)I, respectively, in detecting iodine-positive metastases in patients with differentiated thyroid carcinoma. The study included patients who underwent PET /: CT 24 and 120 h after administration of approximately 25 MBq of (124)I and subsequently underwent imaging 5-10 d after administration of 1-10 GBq of (131)I. For each patient, the intratherapeutic (131)I imaging comprised a whole-body scintigraphy scan and a SPECT/CT scan of the neck to distinguish between metastatic and thyroid remnant tissues. Iodine uptake was rated as a metastatic focus if located outside the thyroid bed. Lesion- and patient-based analyses were performed. The study included 137 patients with 227 metastases iodine-positive on both functional imaging modalities. In the lesion-based analysis, (124)I PET and (131)I imaging detected 98% (223/227) and 99% (225/227) of the iodine-positive metastases, respectively; the level of agreement between (124)I PET and (131)I imaging was 97% (221/227). Four metastases (3 lymph node and 1 bone) in 4 patients were (124)I-negative but (131)I-positive, and 2 lymph node metastases in 2 patients were (131)I-negative but (124)I-positive. In the patient-based analysis, 61 of the 137 patients presented with iodine-positive metastases. (124)I PET and (131)I imaging detected at least one iodine-positive metastasis in 97% (59/61) and 98% (60/61) of the patients, respectively. The level of agreement was 95% (58/61). Both imaging modalities concordantly identified 76 of 137 patients without pathologic iodine uptake. Because of the high level of agreement, pretherapeutic (124)I PET/CT is an adequate methodology in the detection of iodine-positive metastases and can be used as a reliable tool for staging of thyroid cancer patients and individualized treatment planning. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

PubMed

Morita, Koji; Sakamoto, Takahiko; Ota, Shuji; Masugi, Hideo; Chikuta, Ikumi; Mashimo, Yamato; Edo, Naoki; Tokairin, Takuo; Seki, Nobuhiko; Ishikawa, Toshio

2017-01-01

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huysmans, D.A.; Corstens, F.H.; Kloppenborg, P.W.

1991-01-01

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 ({sup 131}I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule.more » The risk of development of hypothyroidism is low if extranodular uptake of {sup 131}I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.« less

A rare cause of hyperthyroidism: functioning thyroid metastases.

PubMed

Gardner, Daphne; Ho, Su Chin

2014-10-09

Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome. 2014 BMJ Publishing Group Ltd.

Effects of thyroidal, gonadal and adrenal hormones on tissue respiration of streaked frog, Rana limnocharis, at low temperature.

PubMed

Gupta, B B; Chakrabarty, P

1990-01-01

In vivo and in vitro effects of thyroidal, gonadal and adrenal hormones were studied on the rate of liver and skeletal muscle respiration in both the sexes of R. limnocharis during active and inactive phases of the annual activity cycle. Triiodothyronine (L-T3) and thyroxine (L-T4) did not stimulate tissue (liver and muscle) respiration in any of the experiments irrespective of season, sex and temperature. Testosterone, estradiol and corticosterone stimulated O2 uptake significantly irrespective of season, sex and temperature. Adrenaline and nor-adrenaline also stimulated tissue respiration significantly during the winter month. Since the ambient temperature was low even during the active phase (max. temperature 21 degrees C), it seems that the frog might have developed tissue sensitivity for gonadal and adrenal hormones at low temperatures when thyroid hormones are calorigenically ineffective.

Iodine deficiency and thyroid disorders.

PubMed

Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes.

PubMed

Schnell, Christian; Shahmoradi, Ali; Wichert, Sven P; Mayerl, Steffen; Hagos, Yohannes; Heuer, Heike; Rossner, Moritz J; Hülsmann, Swen

2015-01-01

Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though the labeling mechanism remains unknown and the efficacy of labeling in different brain regions is heterogeneous. By combining region-specific isolation of astrocytes followed by transcriptome analysis, two-photon excitation microscopy, and mouse genetics, we identified the thyroid hormone transporter OATP1C1 as the SR101-uptake transporter in hippocampus and cortex.

Preoperative localization of parathyroid carcinoma using Tc-99m MIBI.

PubMed

Kitapçi, M T; Tastekin, G; Turgut, M; Caner, B; Kars, A; Barista, I; Bekdik, C

1993-03-01

A patient with parathyroid cancer is presented who underwent Tc-99m MIBI scintigraphy. The Tc-99m MIBI image demonstrated increased accumulation of activity at the lower pole of the left thyroid lobe which was later confirmed as a parathyroid cancer. Uptake by parathyroid cancer must be kept in mind as a cause of increased Tc-99m MIBI accumulation when a disease is in question in the thyroid or parathyroid gland.

Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy.

PubMed

Szumowski, Piotr; Mojsak, Małgorzata; Abdelrazek, Saeid; Sykała, Monika; Amelian-Fiłonowicz, Anna; Jurgilewicz, Dorota; Myśliwiec, Janusz

2016-12-01

The therapeutic activity of 131 I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake ( 131 IU max ) needed for the calculation is usually determined with the use of 131 I. The purpose of the paper was to estimate 131 IU max on the basis of technetium uptake in the thyroid at 20 min ( 99m TcU 20min ). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT 4 , fT 3 , thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131 IU max for each patient was determined according to the levels of 131 I after 24 h ( 131 IU 24h ), while effective half-life (T eff ) according to the measurements of 131 IU 24h and 131 I uptake after 48 h ( 131 IU 48h ). Additionally, on the day before measuring 131 IU 24h , 99m TcU 20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and 131 IU 24h , TRAb and 99m TcU 20min , and 99m TcU 20min and 131 IU 24h . The interdependence between 131 IU 24h and 99m TcU 20min at the level of significance p < 0.05 is described by the following algorithms: 131 IU 24h  = 17.72 × ln ( 99m TcU 20min ) + 30.485, if TRAb < 10 IU/ml, and 131 IU 24h  = 18.03 × ln ( 99m TcU 20min ) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake 131 IU 24h in Graves' disease on the basis of measuring the uptake of 99m TcU 20min . This shortens the time necessary for diagnosis and enables the calculation of 131 I activity using Marinelli's formula.

Silent Thyroiditis

PubMed Central

Walker, Peter

1984-01-01

Silent or painless thyroiditis is a frequent cause of transient hyperthyroidism, which is characterized by recent onset of symptoms in a patient with a normal to modestly enlarged and firm thyroid gland. The hallmarks of the disease are the absence of thyroidal pain or tenderness and a markedly reduced radioiodine uptake. Histologically, the gland is characterized by an important lymphocytic infiltration, occasionally to the point of lymphoid follicle formation. However, other indices of an autoimmune cause are usually absent. The disease appears to have a predilection for the postpartum period. Relapses may occur with subsequent pregnancies. Otherwise, the course is usually benign and transient, requiring moderate doses of β-adrenergic blocking agents for symptomatic relief. No pathogenetic factors are known, but the disease may conceivably have an autoimmune basis, particularly in the postpartum patient. PMID:21278944

Clinical determinants of fluorodeoxyglucose positron emission tomography/computed tomography in differentiated thyroid cancer patients with elevated thyroglobulin and negative (131)iodine whole body scans after (131)iodine therapy.

PubMed

Shamim, Syed Ejaz; Nang, Lee Boon; Shuaib, Ibrahim Lutfi; Muhamad, Nor Asiah

2014-05-01

A cross-sectional prospective study has been conducted on differentiated thyroid cancer (DTC) patients using negative (131)Iodine ((131)I) whole body scans and elevated thyroglobulin (Tg) levels. The main objective of this research was to determine the prevalence of the conversion of differentiated to dedifferentiated thyroid cancer patients during follow up at the Hospital Kuala Lumpur. It has been demonstrated that fluorodeoxyglucose (FDG) uptake is inversely proportional to the iodine concentration and to differentiation of the cells. Thirty-five patients with histologically proven DTC that have undergone total or near total thyroidectomy, and post (131)I radioactive iodine ablation therapy, were selected and prospectively analysed. The patients also had to show at least one negative whole body scan and Tg levels of 10 μg/L and above. The results of the FDG-Positron Emission Tomography/Computed Tomography (PET/CT) were then studied to determine the association and the predictors influencing the outcome by using univariable and multivariable analyses. Out of the thirty-five patients, 60% of them (twenty-one) showed positive results and 40% (fourteen) showed negative. Age, gender, and type of histopathology (HPE) showed significant associations with the positive results of the FDG-PET/CT. The results also showed no correlations observed between the Tg levels and standardised uptake value (SUV)max in the DTC patients with positive disease findings in the FDG-PET/CT. The predictor for this study was age. The prevalence of the conversion of differentiated to dedifferentiated thyroid cancer among patients with negative (131)I and elevated Tg was 60%, with age as the predictor. DTC patients aged 45 year-old and older were seven times more likely to have positive results of FDG-PET/CT imaging.

Clinical Determinants of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin and Negative 131Iodine Whole Body Scans after 131Iodine Therapy

PubMed Central

SHAMIM, Syed Ejaz; NANG, Lee Boon; SHUAIB, Ibrahim Lutfi; MUHAMAD, Nor Asiah

2014-01-01

Background: A cross-sectional prospective study has been conducted on differentiated thyroid cancer (DTC) patients using negative 131Iodine (131I) whole body scans and elevated thyroglobulin (Tg) levels. The main objective of this research was to determine the prevalence of the conversion of differentiated to dedifferentiated thyroid cancer patients during follow up at the Hospital Kuala Lumpur. It has been demonstrated that fluorodeoxyglucose (FDG) uptake is inversely proportional to the iodine concentration and to differentiation of the cells. Methods: Thirty-five patients with histologically proven DTC that have undergone total or near total thyroidectomy, and post 131I radioactive iodine ablation therapy, were selected and prospectively analysed. The patients also had to show at least one negative whole body scan and Tg levels of 10 μg/L and above. The results of the FDG-Positron Emission Tomography/Computed Tomography (PET/CT) were then studied to determine the association and the predictors influencing the outcome by using univariable and multivariable analyses. Results: Out of the thirty-five patients, 60% of them (twenty-one) showed positive results and 40% (fourteen) showed negative. Age, gender, and type of histopathology (HPE) showed significant associations with the positive results of the FDG-PET/CT. The results also showed no correlations observed between the Tg levels and standardised uptake value (SUV)max in the DTC patients with positive disease findings in the FDG-PET/CT. The predictor for this study was age. Conclusion: The prevalence of the conversion of differentiated to dedifferentiated thyroid cancer among patients with negative 131I and elevated Tg was 60%, with age as the predictor. DTC patients aged 45 year-old and older were seven times more likely to have positive results of FDG-PET/CT imaging. PMID:25246834

Ultrasound-guided laser thermal ablation in the treatment of autonomous hyperfunctioning thyroid nodules and compressive nontoxic nodular goiter.

PubMed

Spiezia, Stefano; Vitale, Giovanni; Di Somma, Carolina; Pio Assanti, Angelo; Ciccarelli, Antonio; Lombardi, Gaetano; Colao, Annamaria

2003-10-01

Percutaneous laser thermal ablation (LTA) has been applied in several tumors. In this study we evaluated the safety and long-term efficacy of LTA in the treatment of benign thyroid nodules. Seven patients with autonomous hyperfunctioning thyroid nodule (group A) and five patients with compressive nodular goiter (group B) were treated with LTA. Up to three needles were positioned centrally in the thyroid nodule and laser fiber was placed in the lumen of the needle. Laser illumination was performed reaching a maximal energy deposition of 1800 J per fiber. Thyroid nodule volume, endocrinologic, and clinical evaluation were performed at baseline, 3, and 12 months after the treatment. Scintigraphy was performed at diagnosis and 12 months after the first session in group A. In group A, mean thyroid volume decreased from 3.15 +/- 1.26 mL to 0.83 +/- 0.49 mL (p < 0.001) after 12 months. The treatment induced disappearance of clinical signs and symptoms related to hyperthyroidism; normalization of free triiodothyronine (FT(3)), free thyroxine (FT(4)), and thyrotropin (TSH) serum levels and recovery of extranodular uptake at scintiscan. In group B, mean thyroid volume decreased from 11.14 +/- 4.99 mL to 3.73 +/- 1.47 mL (p < 0.01) after 12 months. Pressure symptoms in the neck, difficulty in swallowing and tracheal displacement improved in all patients. The treatment was well tolerated in both groups of patients. LTA appears to be a valid and safe alternative approach in the treatment of benign thyroid nodules.

Treatment of hyperfunctioning thyroid nodules with percutaneous ethanol injection: Eight years' experience.

PubMed

Monzani, F; Caraccio, N; Goletti, O; Casolaro, A; Lippolis, P V; Cavina, E; Miccoli, P

1998-01-01

The aim of our study was to define the long-term efficacy and safety of percutaneous ethanol injection (PEI) for the treatment of autonomous thyroid nodule (ATN), and to optimise the clinical usefulness of such a therapy. We treated 132 patients with ATN (30 M and 102 F, aged 47.5+/-12.9 years; mean+/-SD), in case other established treatments were refused or contraindicated. Eighty-five patients were affected by toxic adenoma and 47 suffered from pre-toxic nodules. Ethanol was administered weekly under sonographic control, in 7 sessions (range 2-16). During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. Three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra nodular tissue uptake, along with elevated free thyroid hormone and undetectable TSH levels); partial cure (normal free thyroid hormone and low/undetectable TSH levels); complete cure (normal thyroid hormone and TSH levels; restored extra nodular uptake). The patients were followed for up to 8.5 years (median 76 months). PEI therapy was well tolerated by all patients though a mild to moderate local pain occurred in about 30% of sessions. Complete cure was achieved in all pre-toxic patients and in 60 (70.6%) patients with toxic adenoma, while partial cure was observed in 11 cases (12.9%) and failure in 14 (16.5%). A significant shrinkage of nodule volume was observed in all patients (p = 0.0001), while those with toxic nodules larger than 30 mL showed a significantly lower response rate to PEI (p < 0.05). At controls, only one patient developed subclinical hypothyroidism while, among partially cured patients, five relapsed. The administration of methimazole and/or propranolol did not modify PEI outcome. In conclusion, we suggest that PEI therapy may be the treatment of choice in patients with pre-toxic thyroid adenoma where therapy is least necessary- despite the nodule volume. Though ethanol injection therapy of toxic thyroid nodules may be troublesome for the need of multiple sessions, it appears an effective alternative procedure in patients at poor surgical risk, and in younger patients in whom radioiodine is contraindicated. Since a special technical skill in intervention procedures is required, PEI therapy may be suitable only for patients living nearby a trained centre.

Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

PubMed Central

Lakshmanan, Aparna; Doseff, Andrea I.; Ringel, Matthew D.; Saji, Motoyasu; Rousset, Bernard; Zhang, Xiaoli

2014-01-01

Background: Selectively increased radioiodine accumulation in thyroid cells by thyrotropin (TSH) allows targeted treatment of thyroid cancer. However, the extent of TSH-stimulated radioiodine accumulation in some thyroid tumors is not sufficient to confer therapeutic efficacy. Hence, it is of clinical importance to identify novel strategies to selectively further enhance TSH-stimulated thyroidal radioiodine accumulation. Methods: PCCl3 rat thyroid cells, PCCl3 cells overexpressing BRAFV600E, or primary cultured tumor cells from a thyroid cancer mouse model, under TSH stimulation were treated with various reagents for 24 hours. Cells were then subjected to radioactive iodide uptake, kinetics, efflux assays, and protein extraction followed by Western blotting against selected antibodies. Results: We previously reported that Akt inhibition increased radioiodine accumulation in thyroid cells under chronic TSH stimulation. Here, we identified Apigenin, a plant-derived flavonoid, as a reagent to further enhance the iodide influx rate increased by Akt inhibition in thyroid cells under acute TSH stimulation. Akt inhibition is permissive for Apigenin's action, as Apigenin alone had little effect. This action of Apigenin requires p38 MAPK activity but not PKC-δ. The increase in radioiodide accumulation by Apigenin with Akt inhibition was also observed in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβPV/PV mice. Conclusion: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer. PMID:24400871

Comparative effects of in ovo exposure to sodium perchlorate on development, growth, metabolism, and thyroid function in the common snapping turtle (Chelydra serpentina) and red-eared slider (Trachemys scripta elegans).

PubMed

Eisenreich, Karen M; Dean, Karen M; Ottinger, Mary Ann; Rowe, Christopher L

2012-11-01

Perchlorate is a surface and groundwater contaminant found in areas associated with munitions and rocket manufacturing and use. It is a thyroid-inhibiting compound, preventing uptake of iodide by the thyroid gland, ultimately reducing thyroid hormone production. As thyroid hormones influence metabolism, growth, and development, perchlorate exposure during the embryonic period may impact embryonic traits that ultimately influence hatchling performance. We topically exposed eggs of red-eared sliders (Trachemys scripta) and snapping turtles (Chelydra serpentina) to 200 and 177 μg/g of perchlorate (as NaClO(4)), respectively, to determine impacts on glandular thyroxine concentrations, embryonic growth and development, and metabolic rates of hatchlings for a period of 2 months post-hatching. In red-eared sliders, in ovo perchlorate exposure delayed hatching, increased external yolk size at hatching, increased hatchling mortality, and reduced total glandular thyroxine concentrations in hatchlings. In snapping turtles, hatching success and standard metabolic rates were reduced, liver and thyroid sizes were increased, and total glandular thyroxine concentrations in hatchlings were reduced after exposure to perchlorate. While both species were negatively affected by exposure, impacts on red-eared sliders were most severe, suggesting that the slider may be a more sensitive sentinel species for studying effects of perchlorate exposure to turtles. Copyright © 2012 Elsevier Inc. All rights reserved.

Radioactive iodine therapy in cats with hyperthyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turrel, J.M.; Feldman, E.C.; Hays, M.

Eleven cats with hyperthyroidism were treated with radioactive iodine (/sup 131/I). Previous unsuccessful treatments for hyperthyroidism included hemithyroidectomy (2 cats) and an antithyroid drug (7 cats). Two cats had no prior treatment. Thyroid scans, using technetium 99m, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 5 cats and in both lobes in 6 cats. Serum thyroxine concentrations were high and ranged from 4.7 to 18 micrograms/dl. Radioactive iodine tracer studies were used to determine peak radioactive iodine uptake (RAIU) and effective and biological half-lives. Activity of /sup 131/I administered was calculated from peak RAIU, effective half-life, andmore » estimated thyroid gland weight. Activity of /sup 131/I administered ranged from 1.0 to 5.9 mCi. The treatment goal was to deliver 20,000 rad to hyperactive thyroid tissue. However, retrospective calculations based on peak RAIU and effective half-life obtained during the treatment period showed that radiation doses actually ranged from 7,100 to 64,900 rad. Complete ablation of the hyperfunctioning thyroid tissue and a return to euthyroidism were seen in 7 cats. Partial responses were seen in 2 cats, and 2 cats became hypothyroid. It was concluded that /sup 131/I ablation of thyroid tumors was a reasonable alternative in the treatment of hyperthyroidism in cats. The optimal method of dosimetry remains to be determined.« less

Thyroid Isthmus Length and Iodine Turnover as Predictors of Successful Radioactive Iodine Therapy in Patients with Graves' Disease

PubMed Central

Hwang, Sena; Han, Seunghee; Lee, Eun Jig

2017-01-01

Radioactive iodine (RAI) therapy is an effective treatment option for Graves' disease. However, predicting treatment failures after RAI therapy remains controversial. The objective of this study was to investigate the factors associated with the success rate of RAI therapy for treatment of Graves' hyperthyroidism. Thyroid functional outcome, pre-RAI ultrasonographic features, and clinical parameters were evaluated retrospectively in 98 patients followed up for at least 12 months after RAI (mean RAI dose was 11.7 ± 1.8 mCi). Hypothyroidism was achieved in 59 patients (60.2%), and euthyroidism in 16 patients (16.3%), while 23 patients (23.5%) remained hyperthyroid. Age, sex, body mass index, pre-RAI thyroid function, or thyroid-stimulating immunoglobulin levels were not associated with treatment outcome. Length of thyroid isthmus (p = 0.028) and 2- to 24-hour iodine uptake ratios (p = 0.002) were significantly associated with treatment failure, which was defined as a persistent hyperthyroid status after RAI therapy. Patients with a longer isthmus had a higher risk of remaining hyperthyroid, with a threshold for isthmus length of 5.2 mm, with a sensitivity of 69.6% and specificity of 70.3% for treatment success. Measuring the length of the thyroid isthmus can be a simple and useful way to predict RAI treatment outcome. PMID:29358949

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid

PubMed Central

Heitkötter, Birthe; Steinestel, Konrad; Trautmann, Marcel; Grünewald, Inga; Barth, Peter; Gevensleben, Heidrun; Bögemann, Martin; Wardelmann, Eva; Hartmann, Wolfgang; Rahbar, Kambiz; Huss, Sebastian

2018-01-01

Aim PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer. PMID:29515776

Modeled nitrate levels in well water supplies and prevalence of abnormal thyroid conditions among the Old Order Amish in Pennsylvania

PubMed Central

2012-01-01

Background Nitrate is a widespread contaminant of drinking water supplies, especially in agricultural areas. Nitrate intake from drinking water and dietary sources can interfere with the uptake of iodide by the thyroid, thus potentially impacting thyroid function. Methods We assessed the relation of estimated nitrate levels in well water supplies with thyroid health in a cohort of 2,543 Old Order Amish residing in Lancaster, Chester, and Lebanon counties in Pennsylvania for whom thyroid stimulating hormone (TSH) levels were measured during 1995-2008. Nitrate measurement data (1976-2006) for 3,613 wells in the study area were obtained from the U.S. Geological Survey and we used these data to estimate concentrations at study participants' residences using a standard linear mixed effects model that included hydrogeological covariates and kriging of the wells' residuals. Nitrate levels estimated by the model ranged from 0.35 mg/L to 16.4 mg/L N-NO3-, with a median value of 6.5 mg/L, which was used as the cutpoint to define high and low nitrate exposure. In a validation analysis of the model, we calculated that the sensitivity of the model was 67% and the specificity was 93%. TSH levels were used to define the following outcomes: clinical hyperthyroidism (n = 10), clinical hypothyroidism (n = 56), subclinical hyperthyroidism (n = 25), and subclinical hypothyroidism (n = 228). Results In women, high nitrate exposure was significantly associated with subclinical hypothyroidism (OR = 1.60; 95% CI: 1.11-2.32). Nitrate was not associated with subclinical thyroid disease in men or with clinical thyroid disease in men or women. Conclusions Although these data do not provide strong support for an association between nitrate in drinking water and thyroid health, our results do suggest that further exploration of this hypothesis is warranted using studies that incorporate individual measures of both dietary and drinking water nitrate intake. PMID:22339761

Modeled nitrate levels in well water supplies and prevalence of abnormal thyroid conditions among the Old Order Amish in Pennsylvania.

PubMed

Aschebrook-Kilfoy, Briseis; Heltshe, Sonya L; Nuckols, John R; Sabra, Mona M; Shuldiner, Alan R; Mitchell, Braxton D; Airola, Matt; Holford, Theodore R; Zhang, Yawei; Ward, Mary H

2012-02-17

Nitrate is a widespread contaminant of drinking water supplies, especially in agricultural areas. Nitrate intake from drinking water and dietary sources can interfere with the uptake of iodide by the thyroid, thus potentially impacting thyroid function. We assessed the relation of estimated nitrate levels in well water supplies with thyroid health in a cohort of 2,543 Old Order Amish residing in Lancaster, Chester, and Lebanon counties in Pennsylvania for whom thyroid stimulating hormone (TSH) levels were measured during 1995-2008. Nitrate measurement data (1976-2006) for 3,613 wells in the study area were obtained from the U.S. Geological Survey and we used these data to estimate concentrations at study participants' residences using a standard linear mixed effects model that included hydrogeological covariates and kriging of the wells' residuals. Nitrate levels estimated by the model ranged from 0.35 mg/L to 16.4 mg/L N-NO3(-), with a median value of 6.5 mg/L, which was used as the cutpoint to define high and low nitrate exposure. In a validation analysis of the model, we calculated that the sensitivity of the model was 67% and the specificity was 93%. TSH levels were used to define the following outcomes: clinical hyperthyroidism (n = 10), clinical hypothyroidism (n = 56), subclinical hyperthyroidism (n = 25), and subclinical hypothyroidism (n = 228). In women, high nitrate exposure was significantly associated with subclinical hypothyroidism (OR = 1.60; 95% CI: 1.11-2.32). Nitrate was not associated with subclinical thyroid disease in men or with clinical thyroid disease in men or women. Although these data do not provide strong support for an association between nitrate in drinking water and thyroid health, our results do suggest that further exploration of this hypothesis is warranted using studies that incorporate individual measures of both dietary and drinking water nitrate intake.

Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism.

PubMed

Felker, Peter; Bunch, Ronald; Leung, Angela M

2016-04-01

Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40-69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Determining thyroid {sup 131}I effective half-life for the treatment planning of Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willegaignon, Jose; Sapienza, Marcelo T.; Barberio Coura Filho, George

2013-02-15

Purpose: Thyroid {sup 131}I effective half-life (T{sub eff}) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple {sup 131}I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T{sub eff}, these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T{sub eff} for dosimetric purposes. Methods: A total of 50 patients with GD were included in this prospectivemore » study. Thyroidal {sup 131}I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T{sub eff} was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). Results: When considering all the measured points, the representative T{sub eff} for all the patients was 6.95 ({+-}0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 ({+-}0.81), 6.90 ({+-}0.81), and 6.95 ({+-}0.81) days, respectively. According to the mean deviations 2.2 ({+-}2.4)%, 2.1 ({+-}2.0)%, and 0.04 ({+-}0.09)% found in T{sub eff}, calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). Conclusions: T{sub eff} obtained from only two thyroid {sup 131}I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning of Graves' disease.« less

Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism.

PubMed

Nourbakhsh, Mitra; Ahmadpour, Fatemeh; Chahardoli, Behnam; Malekpour-Dehkordi, Zahra; Nourbakhsh, Mona; Hosseini-Fard, Seyed Reza; Doustimotlagh, Amirhossein; Golestani, Abolfazl; Razzaghy-Azar, Maryam

2016-03-01

The essential trace element selenium (Se) is required for thyroid hormone synthesis and metabolism. Selenoproteins contain selenocysteine and are responsible for biological functions of selenium. Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage. Selenoprotein P (SePP) is considered as the plasma selenium transporter to tissues. The aim of this study was to evaluate serum Se and SePP levels, and GPx activity in erythrocytes of children and adolescents with treated Hashimoto's thyroiditis, hypothyroidism, and normal subjects. Blood samples were collected from 32 patients with Hashimoto's thyroiditis, 20 with hypothyroidism, and 25 matched normal subjects. All the patients were under treatment with levothyroxine and at the time of analysis all of the thyroid function tests were normal. GPx enzyme activity was measured by spectrophotometry at 340 nm. Serum selenium levels were measured by high-resolution continuum source graphite furnace atomic absorption. SePP, TPOAb (anti-thyroid peroxidase antibody), and TgAb (anti-thyroglobulin antibody) were determined by ELISA kits. T4, T3, T3 uptake and TSH were also measured. Neither GPx activity nor SePP levels were significantly different in patients with Hashimoto's thyroiditis or hypothyroidism compared to normal subjects. Although GPx and SePP were both lower in patients with hypothyroidism compared to those with Hashimoto's thyroiditis and normal subjects but the difference was not significant. Serum Se levels also did not differ significantly in patients and normal subjects. We did not find any correlation between GPx or SePP with TPOAb or TgAb but SePP was significantly correlated with Se. Results show that in patients with Hashimoto's thyroiditis or hypothyroidism who have been under treatment with levothyroxine and have normal thyroid function tests, the GPx, SePP and Se levels are not significantly different. Copyright © 2015 Elsevier GmbH. All rights reserved.

Can technical characteristics predict clinical performance in PET/CT imaging? A correlation study for thyroid cancer diagnosis

NASA Astrophysics Data System (ADS)

Kallergi, Maria; Menychtas, Dimitrios; Georgakopoulos, Alexandros; Pianou, Nikoletta; Metaxas, Marinos; Chatziioannou, Sofia

2013-03-01

The purpose of this study was to determine whether image characteristics could be used to predict the outcome of ROC studies in PET/CT imaging. Patients suspected for recurrent thyroid cancer underwent a standard whole body (WB) examination and an additional high-resolution head-and-neck (HN) F18-FDG PET/CT scan. The value of the latter was determined with an ROC study, the results of which showed that the WB+HN combination was better than WB alone for thyroid cancer detection and diagnosis. Following the ROC experiment, the WB and HN images of confirmed benign or malignant thyroid disease were analyzed and first and second order textural features were determined. Features included minimum, mean, and maximum intensity, as well as contrast in regions of interest encircling the thyroid lesions. Lesion size and standard uptake values (SUV) were also determined. Bivariate analysis was applied to determine relationships between WB and HN features and between observer ROC responses and the various feature values. The two sets showed significant associations in the values of SUV, contrast, and lesion size. They were completely different when the intensities were considered; no relationship was found between the WB minimum, maximum, and mean ROI values and their HN counterparts. SUV and contrast were the strongest predictors of ROC performance on PET/CT examinations of thyroid cancer. The high resolution HN images seem to enhance these relationships but without a single dramatic effect as was projected from the ROC results. A combination of features from both WB and HN datasets may possibly be a more robust predictor of ROC performance.

Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study.

PubMed

Aschebrook-Kilfoy, Briseis; Shu, Xiao-Ou; Gao, Yu-Tang; Ji, Bu-Tian; Yang, Gong; Li, Hong Lan; Rothman, Nathaniel; Chow, Wong-Ho; Zheng, Wei; Ward, Mary H

2013-02-15

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40-70 years enrolled in 1996-2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow-up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RR(Q4) = 0.93; 95% confidence interval (CI): 0.42-2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RR(Q4) = 2.05; 95%CI: 1.20-3.51), but there was not a monotonic trend with increasing intake (p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RR(Q4) = 1.96; 95%CI: 1.28-2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer. Copyright © 2012 UICC.

Uptake, elimination, and relative distribution of perchlorate in various tissues of channel catfish

USGS Publications Warehouse

Park, J.-W.; Bradford, C.M.; Rinchard, J.; Liu, F.; Wages, M.; Waters, A.; Kendall, R.J.; Anderson, T.A.; Theodorakis, C.W.

2007-01-01

This study was undertaken to determine the kinetics of uptake and elimination of perchlorate in channel catfish, Ictalurus punctatus. Perchlorate - an oxidizer used in solid fuel rockets, fireworks, and illuminating munitions - has been shown to effect thyroid function, causing hormone disruption and potential perturbations of metabolic activities. For the uptake study, catfish were exposed to 100 mg/L sodium perchlorate for 12 h to 5 d in the laboratory. Perchlorate in tissues was analyzed using ion chromatography. The highest perchlorate concentrations were found in the head and fillet, indicating that these tissues are the most important tissues to analyze when determining perchlorate uptake into large fish. To calculate uptake and elimination rate constants for fillet, gills, G-I tract, liver, and head, fish were exposed to 100 ppm sodium perchlorate for 5 days, and allowed to depurate in clean water for up to 20 days. The animals rapidly eliminated the perchlorate accumulated showing the highest elimination in fillet (Ke = 1.67 day -1) and lowest elimination in liver (Ke = 0.79 day -1). ?? 2007 American Chemical Society.

Hyperthyroidism.

PubMed

Maji, D

2006-10-01

Hyperthyroidism is a clinical situation where there is excess thyroid hormones in the circulation due to increased synthesis of hormone from a hyperactive thyroid gland. Common causes are Graves' disease, toxic multinodular goitre and toxic solitary nodule. Excess thyroid hormones in the circulation are also found in thyroiditis (hormone leakage) and excess exogenous thyroxine intake. Thyrotoxicosis is the term applied when there is excess thyroid hormone in the circulation due to any cause. Thyrotoxicosis can be easily diagnosed by high serum level of thyroxine (T4) and triiodothyronine (T3) and low serum level of thyroid stimulating hormone (TSH). Hyperthyroidism is confirmed by high isotope (I 131 or Tc99) uptake by the thyroid gland, while in thyroiditis it will be low. Treatment of hyperthyroidism depends on the underlying cause. Antithyroid drugs, 1131 therapy and surgery are the options of treatment of hyperthyroidism. Surgery is the preferred treatment for toxic adenoma and toxic multinodular goitre, while 1131 therapy may be suitable in some cases. Antithyroid drugs and 1131 therapy are mostly preferred for Graves' disease. Beta-adrenergic blockers are used for symptomatic relief in most patients of thyrotoxicosis due to any cause. Other rare causes of hyperthyroidism like, amiodarone induced thyrotoxicosis, choriocarcinoma, thyrotropin secreting pituitary tumour are difficult to diagnose as well as to treat.

Recurrent Medullary Thyroid Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT: Exploring New Theranostic Avenues.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Parida, Girish Kumar; Singhal, Abhinav; Nalli, Harish; Dattagupta, Shreya; Bal, Chandrasekar

2018-05-01

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.

Outpatient thyroid remnant ablation using repeated low 131-iodine activities (740 MBq/20 mCix2) in patients with low-risk differentiated thyroid cancer.

PubMed

Clerc, Jérôme; Bienvenu-Perrard, Marie; de Malleray, Caroline Pichard; Dagousset, Françoise; Delbot, Thierry; Dreyfuss, Marc; Groussin, Lionel; Marlowe, Robert J; Leger, Françoise Aubène; Chevalier, Alain

2012-03-01

In low-risk differentiated thyroid cancer (DTC), postoperative (131)I remnant ablation should employ a minimum effective activity; reports increasingly suggest efficacy of low activities, e.g. 1110 MBq/30 mCi. OBJECTIVES, DESIGN, PATIENTS, AND INTERVENTIONS: We retrospectively studied the ablation capability and diagnostic utility of the Minidose protocol, two 740-MBq/20 mCi outpatient administrations, 6-18 months apart, plus related diagnostic procedures, in 160 consecutive (near-) totally thyroidectomized low-risk DTC (pT1/N0-Nx) patients. Successful ablation comprised negative 740-MBq whole-body scintigraphy with cervical uptake below 0.1%, negative stimulated thyroglobulin (STg) (<1 ng/ml, negative thyroglobulin antibodies), and negative Doppler ultrasonography (performed around Minidose 2). The study took place at a referral center. Minidose imaging found unsuspected nodal or distant metastases in nine of 160 patients (5.6%). Ablation success rates after one (two) 740-MBq activity (activites) were 75.9% (90.2%) in 145 (132) evaluable imaging-negative patients. Compared with thyroid hormone withdrawal, recombinant human TSH stimulation was associated with higher urinary iodine excretion/creatinine, lower cervical uptake, and more frequent ablation success after the first 740 MBq; success rates no longer differed significantly after both administrations. Patients with STg below 10 ng/ml at Minidose 1 were oftener ablated at Minidose 2 (odds ratio=13.9, 95% confidence interval=2.5-76.4, P<0.003), attaining 92.0% final ablation success after recombinant human TSH preparation, suggesting that one 740-MBq activity should suffice in this subgroup. All 81 evaluable patients with prolonged follow-up (mean 41.8±21.9 months after Minidose 1) had no evidence of disease at the last visit. The Minidose outpatient ablation protocol is effective and diagnostically useful in low-risk DTC.

Genetic Factors That Might Lead to Different Responses in Individuals Exposed to Perchlorate

PubMed Central

Scinicariello, Franco; Murray, H. Edward; Smith, Lester; Wilbur, Sharon; Fowler, Bruce A.

2005-01-01

Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell–surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels. PMID:16263499

The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.

PubMed

Irimie, Alexandru; Piciu, Doina

2017-11-10

The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

PubMed Central

Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.

2011-01-01

Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

[Apathetic hyperthyroidism with heart failure in an elderly patient with Plummer's disease].

PubMed

Narisawa, Manabu; Okada, Yosuke; Arao, Tadashi; Kuno, Fumi; Tanaka, Yoshiya

2014-12-01

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Luchuan; Lv, Bin; Chen, Bo

2015-07-10

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, wasmore » picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.« less

Iodine status and thyroid function of Boston-area vegetarians and vegans.

PubMed

Leung, Angela M; Lamar, Andrew; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N

2011-08-01

Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8-964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3-778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31-1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T(4) (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T(4) (P = 0.14), even when adjusted for multiple variables. U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups.

Iodine Status and Thyroid Function of Boston-Area Vegetarians and Vegans

PubMed Central

LaMar, Andrew; He, Xuemei; Braverman, Lewis E.; Pearce, Elizabeth N.

2011-01-01

Context: Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. Objective: The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. Design and Setting: This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. Subjects: One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Results: Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8–964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3–778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31–1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T4 (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T4 (P = 0.14), even when adjusted for multiple variables. Conclusions: U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups. PMID:21613354

Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.

PubMed

Yavuz, Sahzene; Apolo, Andrea B; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A; Shawker, Thomas; Reynolds, James; Celi, Francesco S

2014-08-01

Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event.

Cabozantinib-Induced Thyroid Dysfunction: A Review of Two Ongoing Trials for Metastatic Bladder Cancer and Sarcoma

PubMed Central

Yavuz, Sahzene; Apolo, Andrea B.; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A.; Shawker, Thomas; Reynolds, James

2014-01-01

Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Results: Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. Conclusion: TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event. PMID:24724719

Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oda, Kenzaburo; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540

Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of pre-hormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tgmore » can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated pre-hormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways. - Highlights: • Follicular Tg increases cathepsin H mRNA and protein levels in rat thyroid cells. • Follicular Tg increases cathepsin H enzyme activity in rat thyroid cells. • After Tg stimulation cathepsin H co-localizes to lysosomes with follicular Tg. • Cathepsin H promotes hormone secretion by lysosome-mediated mechanisms.« less

A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.

PubMed

Pilli, Tania; Brianzoni, Ernesto; Capoccetti, Francesca; Castagna, Maria Grazia; Fattori, Sara; Poggiu, Angela; Rossi, Gloria; Ferretti, Francesca; Guarino, Elisa; Burroni, Luca; Vattimo, Angelo; Cipri, Claudia; Pacini, Furio

2007-09-01

Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.

Asymmetric chorea as presenting symptom in Graves' disease.

PubMed

Park, Jinsung; Kim, Jung-Guk; Park, Sung-Pa; Lee, Ho-Won

2012-04-01

Chorea is an involuntary movement disorder characterized by irregular, brief movements that flow from one body part to another in a non-stereotyped fashion. In rare instances, chorea is associated with autoimmune thyroid disease. Most of them have been related with Hashimoto's encephalopathy and few cases have been related with Graves' disease. Most reported cases have been in women with Graves' disease. We describe a 16-year-old male patient with asymmetric chorea as presenting symptom in Graves' disease. He had no family history of neurological disease. Brain imaging, laboratory findings and electroencephalogram demonstrated no abnormality except for thyroid dysfunction which was proved by thyroid function test, sonography and radioiodine uptake scan. Asymmetric chorea improved over months after anti-thyroid medications. This asymmetry could be explained by difference in increased hypersensitivity or by the difference in the number of dopamine receptors, and an asymmetrical breakdown of blood-brain barrier due to their genetic differences.

Effects of Ammonium Perchlorate on Thyroid Function in Developing Fathead Minnows, Pimephales promelas

PubMed Central

Crane, Helen M.; Pickford, Daniel B.; Hutchinson, Thomas H.; Brown, J. Anne

2005-01-01

Perchlorate is a known environmental contaminant, largely due to widespread military use as a propellant. Perchlorate acts pharmacologically as a competitive inhibitor of thyroidal iodide uptake in mammals, but the impacts of perchlorate contamination in aquatic ecosystems and, in particular, the effects on fish are unclear. Our studies aimed to investigate the effects of concentrations of ammonium perchlorate that can occur in the environment (1, 10, and 100 mg/L) on the development of fathead minnows, Pimephales promelas. For these studies, exposures started with embryos of < 24-hr postfertilization and were terminated after 28 days. Serial sectioning of thyroid follicles showed thyroid hyperplasia with increased follicular epithelial cell height and reduced colloid in all groups of fish that had been exposed to perchlorate for 28 days, compared with control fish. Whole-body thyroxine (T4) content (a measure of total circulating T4) in fish exposed to 100 mg/L perchlorate was elevated compared with the T4 content of control fish, but 3,5,3′-triiodothyronine (T3) content was not significantly affected in any exposure group. Despite the apparent regulation of T3, after 28 days of exposure to ammonium perchlorate, fish exposed to the two higher levels (10 and 100 mg/L) were developmentally retarded, with a lack of scales and poor pigmentation, and significantly lower wet weight and standard length than were control fish. Our study indicates that environmental levels of ammonium perchlorate affect thyroid function in fish and that in the early life stages these effects may be associated with developmental retardation. PMID:15811828

A patient with stress-related onset and exacerbations of Graves disease.

PubMed

Vita, Roberto; Lapa, Daniela; Vita, Giuseppe; Trimarchi, Francesco; Benvenga, Salvatore

2009-01-01

An 18-year-old, nonsmoking woman presented to her general practitioner with a 1-week history of weakness, fatigue, palpitations, nervousness, tremors, insomnia, heat intolerance, and sudden enlargement of a thyroid goiter that had been detected 2 years earlier. The patient's symptoms had started shortly after she experienced emotional stress. Diagnostic work-up disclosed an avid radioactive iodine uptake by the goiter. On ultrasound examination, the thyroid gland was enlarged with a diffusely hypoechogenic structure and intense vascularization. Thyroid scintigraphy with (131)I; ultrasonography of the thyroid gland; and measurements of serum free T(3), free T(4), TSH levels and thyroid autoantibodies, including autoantibodies against thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb). Graves disease, with stress-related onset and subsequent stress-related exacerbations. The patient was treated with methimazole to normalize levels of thyroid hormone and thyroid autoantibodies, and with bromazepam to help her cope with stress. The daily dose of methimazole was kept low during pregnancy. Over the 4 year period when the patient was taking methimazole, exacerbations of hyperthyroidism occurred twice: during her first pregnancy and 9 months after her first delivery. On all three occasions, symptoms were preceded by stressful life events. Further exacerbations were avoided by starting bromazepam treatment soon after the patient experienced stressful events.

Thyrotoxicosis-induced acute myocardial infarction due to painless thyroiditis.

PubMed

Kim, Hee Jin; Jung, Tae Sik; Hahm, Jong Ryeal; Hwang, Seok-Jae; Lee, Sang Min; Jung, Jung Hwa; Kim, Soo Kyoung; Chung, Soon Il

2011-10-01

Thyrotoxicosis influences cardiovascular hemodynamics and can induce coronary vasospasm. Patients with thyrotoxicosis-induced acute myocardial infarction (AMI) are unusual and almost all reported cases have been associated with Graves' disease. Patients with painless thyroiditis show a thyrotoxic phase during the early stages. Here we describe a very rare case of thyrotoxicosis with painless thyroiditis-induced AMI. A 35-year-old Korean man visited the emergency room for a 2-hour duration of typical AMI chest pain. The patient did not have any coronary artery disease (CAD) risk factors. The electrocardiogram showed 3 mm of ST-segment elevation in leads II, III, and aVF, which is consistent with inferior AMI. We immediately treated the patient with aspirin, clopidogrel, and nitroglycerine and performed emergent coronary angiography. Coronary angiography showed normal coronary arteries without any stenotic lesions. Consistent with AMI, cardiac enzyme levels of serum creatine kinase (CK), CK-MB, and troponin-I were also elevated. Laboratory findings showed thyrotoxicosis without any thyroid autoantibodies. A 99m-technetium scintigraphy showed markedly decreased thyroid uptake compatible with thyroiditis. We treated the patient with calcium channel blockers and nitrates. The patient spontaneously recovered normal thyroid function after 6 weeks of observation and did not complain of chest pain. Thyrotoxicosis due to painless thyroiditis provoked AMI in a young man who had no atherosclerotic coronary lesions and no CAD risk factors.

Iodine-131 Therapy and Lacrimal Drainage System Toxicity: Nasal Localization Studies Using Whole Body Nuclear Scintigraphy and SPECT-CT.

PubMed

Ali, Mohammad Javed; Vyakaranam, Achyut Ram; Rao, Jyotsna Eleshwarapu; Prasad, Giri; Reddy, Palkonda Vijay Anand

The objective of this study was to evaluate the influence of dose on nasal localization of radioactive iodine-131 (I-131) following therapy for differentiated thyroid carcinomas. Retrospective evaluation of all patients who underwent post-therapy I-131 whole body scintigraphy and single photon emission computed tomography was performed. Patients were divided into 2 groups; group A were treated with 100 millicurie (mCi) and group B with ≥150 mCi. Databases were reviewed for demographics, diagnosis, and administered dosage of I-131. Whole body scintigraphy images were retrieved and nasal uptake was analyzed and classified as nil to trace, low, moderate, and high uptake and corresponding single photon emission CTs were analyzed for radioactive nasal activity. A total of 100 patients were studied, 50 in each of the groups. The M:F ratio was 1.1:1 (27:23) in group A and 1.5:1 (30:20) in group B. The mean age was 43.12 years and 54.6 years in groups A and B, respectively. Papillary carcinoma of the thyroid was the most common type accounting for 82% (41/50) of patients in group A and 62% (31/50) in group B. Imaging studies revealed nil to trace nasal activity in 80% (40/50) in group A as compared with 56% (28/50) in group B. None of the patients in group A showed high nasal uptake, whereas 4% (2/50) in group B demonstrated such high activity. Intranasal localization of radioactive I-131 was significant in patients receiving a dose of ≥150 mCi. Intranasal localization may partly explain toxicity to nasolacrimal duct and may be a risk factor for subsequent development of nasolacrimal duct obstructions.

[The effect of arotinolol on the thyroid function and the autonomic nerve systems].

PubMed

Fukasawa, N; Iitaka, M; Kitahama, S; Miura, S; Sakurai, S; Kawakami, Y; Ishii, J

1993-01-20

beta-blockers have been accepted as a reasonable adjunct therapy for the treatment of hyperthyroidism. They lessen the sympathetic symptoms such as tachycardia and finger tremor. On the other hand, many studies have demonstrated a decrease in 3, 3', 5-triiodothyronine (T3) during treatment with beta-blockers (especially propranolol). The purpose of this study is to clarify the effect of arotinolol (alpha 1, beta-blocker) on the thyroid functions and autonomic nerve systems (ANS) of patients with Graves' disease. Arotinolol 20mg a day p.o. was given to untreated patients with Graves' disease (n = 16) for 2 weeks. Blood sampling and the ANS function-tests were done before and after the treatment. In addition, the in vitro effects of arotinolol on the cAMP production and the radioactive iodine uptake (RAIU) using rat thyroid cell line FRTL5 were evaluated to examine the direct influence on thyroid cells. Arotinolol improved hyperthyroid symptoms including tachycardia, but had no effect on ANS function-tests. It is of interest that not only T3 but also T4 decreased after the arotinolol treatment. We therefore suspected the direct suppressive effects of arotinolol on the thyroid. There were, however, no in vitro inhibitory effects on the cAMP production and the RAIU in TSH-stimulated FRTL5 cells. The reason why serum T4 levels in patients with untreated Graves' disease have decreased after the treatment of arotinolol could not be clarified. In conclusion, arotinolol is a very useful drug for the initial therapy of patients with Graves' disease to reduce the serum thyroid hormone levels and symptoms of hyperthyroidism when combined with antithyroid drugs.

Difficulties in deciding whether to ablate patients with putatively "low-intermediate-risk" differentiated thyroid carcinoma: do guidelines mainly apply in the centres that produce them? Results of a retrospective, two-centre quality assurance study.

PubMed

Frangos, Savvas; Iakovou, Ioannis P; Marlowe, Robert J; Eftychiou, Nicolaos; Patsali, Loukia; Vanezi, Anna; Savva, Androulla; Mpalaris, Vassilis; Giannoula, Evanthia I

2015-12-01

We determined the reasons for radioiodine thyroid remnant ablation, and the procedure's necessity based on postsurgical remnant size, in patients with putatively "low-intermediate-risk" differentiated thyroid carcinoma (DTC). We identified key clinicopathological, treatment and remnant characteristics, and factors associated with remnant size in 336 patients with pT1/2, M0 DTC ablated during the period September 2010 to October 2013 at one Cypriot or one Greek referral centre. Clinicopathological/treatment characteristics were compiled from charts. Experienced nuclear medicine physicians rated the numbers/intensities of uptake foci in the thyroid bed on postablation planar scintigrams using scales of 0-4 points and 0-3 points, respectively. The product of these scores was taken as the "remnant score" that ranged from 0 (no remnant) to 12 (multiple remnants, intense uptake). DTC was predominantly papillary. The median [25th-75th percentile] longest primary tumour diameter was 1.0 cm [0.7-1.5 cm]. Despite favourable histotypes and primary tumour classifications, patients often had preablation characteristics suggesting elevated or uncertain risk: 31.0% of patients (104 of 336) had primary tumour multifocality, 22.0% (74) had confirmed cervical lymph node metastases, 37.2% (125) had unknown nodal status, and 38.1% (128) had antithyroglobulin antibody seropositivity. The median [25th-75th percentile] remnant score was 4 [2-6]; 39.9% of patients (134 of 336) had scores ≥6. For the entire cohort, T or N stages (r ≤ 0.174, P ≤ 0.05) correlated positively with the remnant score in a univariate Spearman analysis. The numbers of patients referred by the surgeon, cervical lymph nodes excised and metastatic nodes excised correlated negatively (r ≤ 0.243, P ≤ 0.038) with the remnant score, and the first two factors independently predicted the remnant score (P ≤ 0.037) in a multivariate analysis. Patients with putatively "low-intermediate-risk" DTC frequently had disease characteristics denoting high or uncertain risk, suggesting that "selective" radioiodine ablation in such patients may seldom be applicable outside international centres of excellence. Proxies for surgeon experience and surgical completeness correlated with remnant number/uptake intensity and may aid ablation-related decision-making.

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

PubMed

Iwata, Masahiro; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Fujita, Toru; Konishi, Junji

2002-06-01

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.

TPA induces a block of differentiation and increases the susceptibility to neoplastic transformation of a rat thyroid epithelial cell line.

PubMed

Portella, G; Vitagliano, D; Li, Z; Sferratore, F; Santoro, M; Vecchio, G; Fusco, A

1998-01-01

The PC Cl 3 cell line is a well-characterized epithelial cell line of rat thyroid origin. This cell line retains in vitro the typical markers of thyroid differentiation: thyroglobulin (TG) synthesis and secretion, iodide uptake, thyroperoxidase (TPO) expression, and dependency on TSH for growth. Although the differentiated phenotype of thyroid cells has been relatively well described, the molecular mechanisms that regulate both differentiation and neoplastic transformation of thyroid cells still need to be investigated in detail. Protein kinase C (PKC), the target of tetradecanoylphorbol acetate (TPA), regulates growth and differentiation of several cell types. Here we show that treatment of PC Cl 3 cells with TPA induces an acute block of thyroid differentiation. TPA-treated PC Cl 3 cells are unable to trap iodide and the expression levels of thyroglobulin, TSH receptor, and TPO genes are drastically reduced by TPA treatment. This differentiation block is not caused by a reduced expression of one of the master genes of thyroid differentiation, the thyroid transcription factor 1 (TTF-1). TPA-treated PC Cl 3 cells display an increased growth rate indicating that, in addition to the differentiation block, TPA also significantly affects the growth regulation of thyroid cells. Finally, TPA treatment dramatically increases the number of transformation foci induced in PC Cl 3 cells by retroviruses carrying v-Ki-ras, v-Ha-ras, and v-mos oncogenes. These findings support the notion that the PKC pathway can influence proliferation, differentiation, and neoplastic transformation of thyroid cells in culture.

Nivolumab-induced thyroid dysfunction in patients with lung cancer.

PubMed

Ramos-Levi, Ana M; Rogado, Jacobo; Sanchez-Torres, Jose Miguel; Colomer, Ramón; Marazuela, Mónica

2018-06-14

Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of Tc-99 m thyroid scans in borderline congenital hypothyroidism.

PubMed

Oren, Asaf; Wang, Michael Ke; Brnjac, Lori; Mahmud, Farid H; Palmert, Mark R

2016-03-01

Mild or borderline congenital hypothyroidism [often referred to as mild neonatal hyperthyrotropinemia (MNH)] is characterized by an abnormal newborn screen (NBS), followed by mildly elevated TSH and normal FT4 on confirmatory testing. This condition is increasingly observed, but data regarding optimal management are limited. Examine the use of routine technetium thyroid scanning (TS) in the management of MNH. Retrospective study of infants with MNH between 2000 and 2011. We assessed the clinical course of infants with MNH according to TS results; as a comparator, infants with classic congenital hypothyroidism (CH) were analysed in parallel. We identified 69 infants (52% boys) with MNH and 164 (34% boys) with classic CH. TS results were divided into four subgroups: no uptake in 7% of MNH vs 24% of classic CH (P < 0·01), decreased uptake/anatomical abnormalities in 39% vs 46% (p = NS), increased uptake in 35% vs 26% (p = NS) and normal uptake in 19% vs 4% (P < 0·01). In MNH, neither NBS-TSH, confirmatory TSH and FT4, mean LT-4 treatment doses and number of dose escalations, nor post-treatment FT4 and TSH differed among the four subgroups. In contrast, clinical features in infants with classic CH differed among the subgroups. Among MNH infants who reached 3 years of age, trial-off treatment was successful in 6 of 11 (55%) with no apparent difference in success rates among TS subgroups. The information provided by TS during evaluation of MNH does not predict clinical course; obtaining these scans in infants with MNH may not be an effective use of healthcare resources. © 2015 John Wiley & Sons Ltd.

Estimated dose rates to members of the public from external exposure to patients with {sup 131}I thyroid treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewji, S., E-mail: dewjisa@ornl.gov; Bellamy, M.; Leggett, R.

Purpose: Estimated dose rates that may result from exposure to patients who had been administered iodine-131 ({sup 131}I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered {sup 131}I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with {sup 131}I. Tissue attenuation and iodine biokinetics were considered in the patient in a larger comprehensive effort to improvemore » external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the {sup 131}I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of {sup 131}I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after {sup 131}I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of {sup 131}I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for {sup 131}I patients with normal thyroid uptake (peak thyroid uptake of ∼27% of administered {sup 131}I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ∼4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ∼3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with {sup 131}I therapy, consideration must be given to (patient- and case-specific) administered {sup 131}I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. The method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Evidence of Prostate-Specific Membrane Antigen Expression in Metastatic Differentiated Thyroid Cancer Using 68Ga-PSMA-HBED-CC PET/CT.

PubMed

Verma, Priyanka; Malhotra, Gaurav; Agrawal, Ritesh; Sonavane, Sunita; Meshram, Vilas; Asopa, Ramesh V

2018-06-12

Prostate-specific membrane antigen (PSMA) overexpression is not restricted to prostate cancer, but it has also been demonstrated in gliomas, lung cancer, and in tumor neovasculature. Systematic studies exploring PSMA uptake in thyroid tumors are lacking. The aim of this pilot study was to assess PSMA expression in patients with metastatic differentiated thyroid cancer (mDTC). Ten patients of mDTC harboring 32 lesions (5 men; age range, 38-65 years; mean age, 50 years) underwent prospective evaluation with radioiodine (I), F-FDG PET, and Ga-PSMA-HBED-CC PET scans as per the institution protocol. PSMA expression (SUVmax) was compared with F-FDG and I scan findings in all patients. Lesions were radioiodine avid in 8 patients, whereas 2 were classified as thyroglobulin elevation with negative iodide scintigraphy (TENIS) patients. All patients with iodine-avid metastatic disease showed substantial PSMA uptake. PSMA PET detected 30/32 total lesions (93.75%; SUVmax ranging from 4.86 to 101.81 with median SUVmax of 31.35), whereas FDG PET/CT was positive in 23/32 lesions (81.85%). Twenty-one (70%) of 30 lesions that showed PSMA expression were localized to the bones. PSMA localized a lesion in each of the 2 TENIS patients similar to FDG PET scan. Ga-PSMA-HBED-CC PET/CT is a potentially useful imaging modality in patients of mDTC with most (70%) of PSMA expressing metastasis being localized to the bones. PSMA PET/CT could be useful for identifying patients with limited therapeutic options (eg, TENIS) who might benefit from PSMA-targeted radionuclide therapy.

Anaplastic Carcinoma and Toxic Multinodular Goiter: An Unusual Presentation

PubMed Central

Marcelino, Mafalda; Marques, Pedro; Lopes, Luis; Leite, Valeriano; de Castro, João Jácome

2014-01-01

A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far. PMID:25759806

Growth stimulating antibody, as another predisposing factor of Graves' disease (GD): analysis using monoclonal TSH receptor antibodies derived from patients with GD.

PubMed

Ihara, Yoshiaki; Kanda, Yasunari; Seo, Marie; Watanabe, Yasuhiro; Akamizu, Takashi; Tanaka, Yuji

2012-01-01

TSH receptor antibody (TRAb) is clinically classified into thyroid stimulating antibody (TSAb) and thyroid-stimulation blocking antibody (TSBAb). Although the former is considered to cause Graves' disease (GD), its activity does not necessarily reflect hormone production and goiter size. Moreover, uptake of 99mTcO4(-), the best indicator for GD, is correlated with activity of TSH binding inhibitor immunoglobulin better than activity of TSAb. Because uptake of 99mTcO4(-) reflects thyroid volume, these observations suggest that there exist TRAb with thyrocyte growth stimulating activity (GSA) other than TSAb. In this study, we analyzed GSA of monoclonal TRAb established from patients with GD or idiopathic myxedema (IME). GSA was measured as the degree of FRTL-5 cell growth stimulated by each TRAb. The signaling pathways of the cell growth were pharmacologically analyzed. The cell growth stimulated by TSH was strongly suppressed by protein kinase A (PKA) inhibitor, but was not affected by extracellular signal regulated kinase kinase (MEK) inhibitor. Although TSAb from GD stimulated the cell growth, both inhibitors suppressed it. Surprisingly, the cell growth was also induced by TSBAb from GD and was only suppressed by MEK inhibitor. TSBAb from IME did not have GSA and attenuated the cell growth stimulated by TSH. We concluded that 1; in GD, not only TSAb but some TSBAb could stimulate thyrocyte growth. 2; TSBAb might be classified with respect to their effects on thyrocyte growth; i.e., thyrocyte growth stimulating antibody and thyrocyte growth-stimulation blocking antibody.

Linking loss of sodium-iodide symporter expression to DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lyckesvärd, Madeleine Nordén; Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg; Kapoor, Nirmal

Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1 nM) calicheamicin blocked NIS mRNA expression andmore » transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. - Highlights: • DNA damage inhibits polarized iodide transport in normal thyroid cells. • Down-regulation of NIS expression is mediated by activation of the ATM kinase. • Long-term ATM inhibition also represses NIS-mediated iodide transport. • IGF-1 rescues NIS expression and iodide transport in DNA-damaged cells.« less

Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?

PubMed

Mooradian, Arshag D

2008-01-01

Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.

Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy.

PubMed

Gurgul, Edyta; Sowinski, Jerzy

2011-01-01

Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.

In vitro screening for potential chemical inhibitors of deiodinase type 1 activity

EPA Science Inventory

Control of thyroid hormone (TH) signaling in vertebrates is dependent upon multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and more...

Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.

PubMed

Sáez, Carmen; Martínez-Brocca, M Asunción; Castilla, Carolina; Soto, Alfonso; Navarro, Elena; Tortolero, María; Pintor-Toro, José A; Japón, Miguel A

2006-04-01

Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. The study was conducted at a tertiary university hospital. Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.

Pendulum swings from hypo- to hyperthyroidism: thyrotoxicosis after severe hypothyroidism following neck irradiation in a patient with a history of Hodgkin's lymphoma.

PubMed

Lewandowski, Krzysztof; Dąbrowska, Katarzyna; Makarewicz, Jacek; Lewiński, Andrzej

2016-01-01

A change in a thyrometabolic state from severe hypothyroidism to thyrotoxicosis is very uncommon, but possible in some circumstances. A 27-year old female presented with clinical and biochemical thyrotoxicosis with a previous history chemo- and radiotherapy (including the neck region) for a Hodgkin's lymphoma (at the age of 18). At the age of 20 this was followed by severe hypothyrodism [TSH > 100 μIU/mL (reference range: 0.27-4.2)]. She was stated on L-thyroxine, but the dose was later reduced and subsequently discontinued. She had significantly elevated titres of both anti-thyroid peroxidase antibodies and anti-TSH-receptor antibodies throughout the course of disease. Thyroid scintigraphy revealed a normal and homogenous iodine uptake. We suspect that a gradual switch from thyroid-blocking to thyroid-stimulating antibodies resulted in development of an overt thyrotoxicosis, possibly with a contributory effect of neck irradiation on her autoimmune status.

Chronic cyanide exposure: a clinical, radioisotope, and laboratory study.

PubMed Central

El Ghawabi, S H; Gaafar, M A; El-Saharti, A A; Ahmed, S H; Malash, K K; Fares, R

1975-01-01

The effect of chronic cyanide exposure in the electroplating sections of three factories employing 36 workers was studied and compared with a control group. The concentration of cyanides to which the workers were exposed was measured. The regression line showing the relationship between thiocyanates in urine and the concentration of cyanides in the air was plotted. Increased percentages of haemoglobin and lymphocyte count were present in all exposed workers, in addition to punctate basophilia in 28 workers. Cyanmethaemoglobin was found to be characteristic. Apart from other complaints, two men with psychosis similar to one case reported in therapeutic thiocyanate intoxication were found. Twenty of the workers had thyroid enlargements to a variable degree and consistency, in two of whom it resembled lymphadenoid goitre. Thyroid 131I uptakes at 4 and 24 hours were significantly higher than in the controls, while 131PBI was unchanged. The reason for this iodine deficiency-like action is discussed. PMID:1156569

A Study of the Cost Savings Potential of the Military - Civilian Health Services Partnership Program in the Nuclear Medicine and Radioimmunoassay Services at Ireland Army Community Hospital, Fort Knox, Kentucky

DTIC Science & Technology

1989-01-01

Esophageal Studies Patient 1 Sequential Images for Transit and or Reflux 30 Computer Acq/Process 20 (b) Stomach Patient 1 Sequential Images Transit...132 141 119 113 150 159 152 124 1715 Liver-Spleen 8 12 7 9 7 5 6 14 5 13 12 12 110 Renal 10 9 19 8 7 8 15 8 7 9 7 7 114 Renal Reflux 4 2 1 0 0 0 0 2 0 0...Scan 0 0 0 0 0 0 0 0 0 1 0 0 Gastric Reflux 0 0 0 0 0 0 0 1 0 1 0 0 2 1-123 Thyroid 11 3 5 9 9 7 10 7 9 11 7 14 102 Thyroid Uptake 11 S 5 9 9 7 10 7 9

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

PubMed

Zhao, Zitong; Lee, Yu Jin; Zheng, Shuwei; Khor, Li Yan; Lim, Kok Hing

2018-05-31

IgG4-related disease of the thyroid gland is a recently recognized subtype of thyroiditis, often with rapid progression requiring surgical treatment. It is considered as a spectrum of disease varying from early IgG4-related Hashimoto's thyroiditis (HT) pattern to late fibrosing HT or Riedel's thyroiditis patterns. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over 3 years and subclinical hypothyroidism. Computed tomography (CT) scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed a limited number of follicular epithelial cell groups with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of 'atypia of undetermined significance'. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate and fibrosis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. The overall features suggest the diagnosis of IgG4-related disease of the thyroid gland in the form of IgG4-related HT. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids for treatment of IgG4-related disease.

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8.

PubMed

Johannes, Jörg; Jayarama-Naidu, Roopa; Meyer, Franziska; Wirth, Eva Katrin; Schweizer, Ulrich; Schomburg, Lutz; Köhrle, Josef; Renko, Kostja

2016-04-01

Thyroid hormones (THs) are charged and iodinated amino acid derivatives that need to pass the cell membrane facilitated by thyroid hormone transmembrane transporters (THTT) to exert their biological function. The importance of functional THTT is affirmed by the devastating effects of mutations in the human monocarboxylate transporter (MCT) 8, leading to a severe form of psychomotor retardation. Modulation of THTT function by pharmacological or environmental compounds might disturb TH action on a tissue-specific level. Therefore, it is important to identify compounds with relevant environmental exposure and THTT-modulating activity. Based on a nonradioactive TH uptake assay, we performed a screening of 13 chemicals, suspicious for TH receptor interaction, to test their potential effects on THTT in MCT8-overexpressing MDCK1-cells. We identified silymarin, an extract of the milk thistle, to be a potent inhibitor of T3 uptake by MCT8. Because silymarin is a complex mixture of flavonolignan substances, we further tested its individual components and identified silychristin as the most effective one with an IC50 of approximately 100 nM. The measured IC50 value is at least 1 order of magnitude below those of other known THTT inhibitors. This finding was confirmed by T3 uptake in primary murine astrocytes expressing endogenous Mct8 but not in MCT10-overexpressing MDCK1-cells, indicating a remarkable specificity of the inhibitor toward MCT8. Because silymarin is a frequently used adjuvant therapeutic for hepatitis C infection and chronic liver disease, our observations raise questions regarding its safety with respect to unwanted effects on the TH axis.

Perchlorate Clinical Pharmacology and Human Health: A Review

PubMed Central

Soldin, Offie Porat; Braverman, Lewis E.; Lamm, Steven H.

2013-01-01

Summary Potassium perchlorate has been used at various times during the last 50 years to treat hyperthyroidism. Since World War II ammonium perchlorate has been used as a propellant for rockets. In 1997, the assay sensitivity for perchlorate in water was improved from 0.4 mg/L (ppm) to 4 µg/L (ppb). As a result, public water supplies in Southern California were found to contain perchlorate ions in the range of 5 to 8 ppb, and those in Southern Nevada were found to contain 5 to 24 ppb. Research programs have been developed to assess the safety or risk from these exposures and to assist state and regulatory agencies in setting a reasonable safe level for perchlorate in drinking water. This report reviews the evidence on the human health effects of perchlorate exposure. Perchlorate is a competitive inhibitor of iodine uptake. All of its pharmacologic effects at current therapeutic levels or lower are associated with inhibition of the sodium-iodide symporter (NIS) on the thyroid follicular cell membrane. A review of the medical and occupational studies has been undertaken to identify perchlorate exposure levels at which thyroid hormone levels may be reduced or thyrotropin levels increased. This exposure level may begin in the 35 to 100 mg/d range. Volunteer studies have been designed to determine the exposure levels at which perchlorate begins to affect iodine uptake in humans. Such effects may begin at levels of approximately 1 mg/d. Environmental studies have assessed the thyroidal health of newborns and adults at current environmental exposures to perchlorate and have concluded that the present levels appear to be safe. Whereas additional studies are underway both in laboratory animals and in the field, it appears that a safe level can be established for perchlorate in water and that regulatory agencies and others are now trying to determine that level. PMID:11477312

Evidence of the Presence of Thyroid Hormones in Achatina fulica Snails.

PubMed

Lustrino, Danilo; Silva, Alba C M; Araujo, Iracema G; Tunholi, Victor M; Tunholi-Alves, Vinícius M; Castro, Rosane N; Carvalho, Denise P; Pinheiro, Jairo; Marassi, Michelle P

2017-01-01

The objective of this study was to identify thyroid hormones and to examine their putative site of synthesis in Achatina fulica snails. For this purpose, radioimmunoassays were performed for T3 and T4 before and after long starvation with or without hemolymph deproteinization. Sodium/iodide symporter activity in vivo was analyzed through 125I administration with and without KClO4 pretreatment. Only T4 was detected, and its concentration decreased due to starvation or deproteinization. However, high-performance liquid chromatography analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not detected in the A. fulica hemolymph. The sodium/iodide symporter activity was greater in cerebral ganglia than digestive gland, but KClO4 treatment did not inhibit iodide uptake in any of the tissues analyzed. Altogether, our data confirm for the first time the presence of thyroid hormones in A. fulica snails and suggest their participation in the metabolism control in this species, although the putative site of hormone biosynthesis remains to be elucidated.

Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis.

PubMed

Iqbal, Ayesha A; Burgess, Elizabeth H; Gallina, Daniel L; Nanes, Mark S; Cook, Curtiss B

2003-01-01

To present two cases of hypercalcemia associated with thyrotoxicosis and to describe serial biochemical findings during the course of treatment of hyperthyroidism. We report two cases, illustrate the changes in serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis, and compare our findings with those in previous studies. Hypercalcemia attributable to thyrotoxicosis is well documented, but the mechanism for the hypercalcemia is incompletely understood. Our first patient had a complicated medical history and several potential causes of hypercalcemia, including recurrent hyperparathyroidism, metastatic breast cancer, and relapse of previously treated thyrotoxicosis. A suppressed parathyroid hormone level and negative bone and computed tomographic scans excluded the first two factors. After thyroid ablation with 131I, the serum calcium and thyroxine levels decreased, and the parathyroid hormone and 1,25-dihydroxyvitamin D3 levels normalized. Our second patient, who was referred to our institution with a preliminary diagnosis of hypercalcemia associated with malignant disease and who had no symptoms of hyperthyroidism, was found to have a high free thyroxine level, diffuse enlargement of the thyroid, and high uptake (58%) of 123I on a thyroid scan. After thyroid ablation, the serum calcium, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone levels normalized, and the free thyroxine level declined. The probable pathogenesis of hypercalcemia in thyrotoxicosis is reviewed with respect to thyroid hormone and its effect on bone turnover. Physicians should consider thyrotoxicosis in the differential diagnosis of hypercalcemia.

Hyperthyroidism. Causes, clinical features, and diagnosis.

PubMed

Spaulding, S W; Lippes, H

1985-09-01

The usual patient with hyperthyroidism has Graves' disease: If serum levels of thyroid hormone are clearly elevated, the presence of infiltrative ophthalmopathy or pretibial myxedema is probably sufficient for establishing the diagnosis. However, if the ancillary findings of Graves' are not present, the radioactive iodine uptake should be determined to rule out other possible etiologies of hyperthyroidism. Signs of hyperthyroidism may be subtle or misleading, particularly in the elderly; the well-informed clinician keeps the diagnosis in mind, and if the initial thyroid hormone tests are not definitive, employs additional tests that are cost-effective in the individual clinical situation.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

2017-02-06

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

NF-κB p65 Subunit Mediates Lipopolysaccharide-Induced Na+/I− Symporter Gene Expression by Involving Functional Interaction with the Paired Domain Transcription Factor Pax8

PubMed Central

Nicola, Juan Pablo; Nazar, Magalí; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Masini-Repiso, Ana María

2010-01-01

The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a variety of biological responses. Na+/I− symporter (NIS)-mediated iodide uptake is the main rate-limiting step in thyroid hormonogenesis. We have recently reported that LPS stimulates TSH-induced iodide uptake. Here, we further analyzed the molecular mechanism involved in the LPS-induced NIS expression in Fisher rat thyroid cell line 5 (FRTL-5) thyroid cells. We observed an increase in TSH-induced NIS mRNA expression in a dose-dependent manner upon LPS treatment. LPS enhanced the TSH-stimulated NIS promoter activity denoting the NIS-upstream enhancer region (NUE) as responsible for the stimulatory effects. We characterized a novel putative conserved κB site for the transcription factor nuclear factor-κB (NF-κB) within the NUE region. NUE contains two binding sites for the transcription factor paired box 8 (Pax8), main regulator of NIS transcription. A physical interaction was observed between the NF-κB p65 subunit and paired box 8 (Pax8), which appears to be responsible for the synergic effect displayed by these transcription factors on NIS gene transcription. Moreover, functional blockage of NF-κB signaling and site-directed mutagenesis of the κB cis-acting element abrogated LPS stimulation. Silencing expression of p65 confirmed its participation as an effector of LPS-induced NIS stimulation. Furthermore, chromatin immunoprecipitation corroborated that NIS is a novel target gene for p65 transactivation in response to LPS. Moreover, we were able to corroborate the LPS-stimulatory effect on thyroid cells in vivo in LPS-treated rats, supporting that thyrocytes are capable of responding to systemic infections. In conclusion, our results reveal a new mechanism involving p65 in the LPS-induced NIS expression, denoting a novel aspect in thyroid cell differentiation. PMID:20667985

Screening the ToxCast Phase 1 chemical library for inhibition of deiodinase type 1 activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper TH signaling. Deiodinase enzymes catalyze iodide release from THs to interconvert THs between active a...

Screening the ToxCast Phase I Chemical Library for inhibition of Deiodinase Type I enzyme activity

EPA Science Inventory

Thyroid hormone (TH) signaling in vertebrates is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and...

Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California.

PubMed

Steinmaus, Craig; Pearl, Michelle; Kharrazi, Martin; Blount, Benjamin C; Miller, Mark D; Pearce, Elizabeth N; Valentin-Blasini, Liza; DeLorenze, Gerald; Hoofnagle, Andrew N; Liaw, Jane

2016-06-01

Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. We evaluated the potential effects of low environmental exposures to perchlorate on thyroid function. Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County, California, during 2000-2003, a period when much of the area's water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 μg/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. The median urinary perchlorate concentration was 6.5 μg/L, about two times higher than in the general U.S. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) [regression coefficient (β) = -0.70; 95% CI: -1.06, -0.34], decreasing free thyroxine (fT4) (β = -0.053; 95% CI: -0.092, -0.013), and increasing log10 thyroid-stimulating hormone (β = 0.071; 95% CI: 0.008, 0.133). These results suggest that environmental perchlorate exposures may affect thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment. Steinmaus C, Pearl M, Kharrazi M, Blount BC, Miller MD, Pearce EN, Valentin-Blasini L, DeLorenze G, Hoofnagle AN, Liaw J. 2016. Thyroid hormones and moderate exposure to perchlorate during pregnancy in women in Southern California. Environ Health Perspect 124:861-867; http://dx.doi.org/10.1289/ehp.1409614.

Thyrotropin Binding Inhibiting Antibody (TBIAb) in Graves’ Disease

PubMed Central

Cho, Won Yong; Choi, Hyang Hee; Chun, Hun Jae; Ahn, Il-Min

1988-01-01

To determine the nature of TBIAb in Graves’ disease, TBIAb was measured and correlated to various clinical, thyroid functional indices and thyroid autoantibodies. The incidence of TBIAb in untreated Graves’ patients, patients in treatment and those in remission was 70.9%, 53.1% and 19.2%, respectively. With respect to clinical indices, there was no correlation between TBIAb and the presence of exophthalmos or periodic paralysis, onset age, diseage duration or sex, but goiter size on initial examination did show significant correlation (r=0.95). Regarding the indices of thyroid function, 20min 99m-Tc uptake (r=0.28), free T4 index (r=0.39) and free T3 index (r=0.40) were well correlated to TBIAb activity. Also Grave’s patients with strong antimicrosomal activity exhibited a high incidence of TBIAb positiveness. PMID:2908684

Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of Thyroid Remnant.

PubMed

Ma, Chao; Feng, Fang; Wang, Shaoyan; Fu, Hongliang; Wu, Shuqi; Ye, Zhiyi; Chen, Suyun; Wang, Hui

2017-06-01

Chinese data on the efficacy of low- and high-dose radioiodine for thyroid remnant are still absent. The aim of the study was to investigate whether a low dose of radioiodine is as effective as a high dose for remnant ablation in Chinese patients. Patients presenting for radioiodine ablation in the authors' department were included. Inclusion criteria were aged ≥16 years, total or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N stage, and M0. All patients were randomly allocated to either the high-dose group of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response to treatment was defined as successful or unsuccessful after a six- to nine-month interval. Ablation was considered to be successful if patients fulfilled the following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body scanning and a negative level of serum thyroglobulin. There were 327 patients enrolled between January 2013 and December 2014. More than 95% had papillary thyroid cancer. Data could be analyzed for 278 cases (M age  = 44 years; 71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose group, and 86.2% in the high-dose group. There was no difference between the two groups (p = 0.509). In Chinese patients with differentiated thyroid carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a high dose of 3700 MBq for thyroid remnant ablation.

Effects of water temperature on perchlorate toxicity to the thyroid and reproductive system of Oryzias latipes.

PubMed

Lee, Sangwoo; Ji, Kyunghee; Choi, Kyungho

2014-10-01

Water temperature is expected to increase in many parts of the world due to global climate change. The change in water temperature may affect ecosystems through alterations of the chemical properties or by affecting the susceptibility of organisms. Perchlorate can disrupt thyroid function of an organism by inhibiting iodide uptake. In the present study, the effect of water temperature on perchlorate toxicity was evaluated using Japanese medaka (Oryzias latipes). Pairs of adult medaka fish were exposed to a sublethal concentration of sodium perchlorate (100mg/L) and a control, at a 'low' (26°C), 'medium' (29°C) or 'high' water temperature (33°C) for seven days. The effects of the water temperature on reproduction, thyroid hormones and cortisol concentrations were determined. Transcription of several genes related to thyroid function and stress were also investigated. Significant down-regulation of thyroid hormone receptor alpha (THR-α) and beta (THR-β) transcripts and up-regulation of deiodinase 2 (DIO2) transcripts were observed in the fish exposed to perchlorate. Thyroxine (T4) concentrations were decreased, while triiodothyronine (T3) levels remained constant following exposure to perchlorate, and this effect became more pronounced under the high water temperature conditions (33°C). Up-regulation of the DIO2 gene may explain these observations. The total number of spawned eggs decreased slightly as the water temperature increased, and this reduction became significant when fish were exposed to perchlorate. Our observations indicate that exposure to perchlorate could affect thyroid function and overall reproductive fitness, and these effects could be aggravated under high water temperatures. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of iodine-131-induced early thyroid hormone variations in Graves' disease.

PubMed

Xu, Feng; Gu, Aichun; Pan, Yifan; Yang, Liwen; Ma, Yubo

2016-11-01

This prospective study aimed to assess iodine-131 (I)-induced early thyroid hormone variations in Graves' disease (GD) and determine the associated factors. One hundred and seventy-one GD patients treated with I were evaluated (47 men, 124 women). I was administered at 9.0±4.9 mCi on average. Serum free triiodothyronine and free thyroxin were measured within 24 h before treatment and 8 (3-14) days after treatment. Patients were divided into increase, no change, and decrease groups, respectively, on the basis of hormone variations after treatment. χ-Test, analysis of variance, and the Kruskal-Wallis test were used to compare groups in terms of sex, age, course of disease, thyroid stimulating hormone receptor antibodies, antithyroid drug (ATD) pretreatment time, time of ATD discontinuation before I treatment, 24 h thyroid I uptake, thyroid weight, I activity, and I activity/thyroid weight (μCi/g). The Spearman method was used for correlation analyses. Twenty-seven, 20, and 124 cases were assigned to increase, no change, and decrease groups, respectively. Significant differences were found among groups in the time of ATD discontinuation before I treatment [the median duration for methimazole was 11 (5-26), 16 (10-30), and 21 (1-30) days, P=0.000, the median duration for propylthiouracil was 12.5 (5-24), 22 (11-26), and 26 (21-30) days, P=0.000], thyroid weight (93.5±33.6, 90.3±48.8, and 74.1±26.0 g, P=0.003), and μCi/g (84.8±11.8, 100.4±24.9, and 121.1±44.0 μCi/g, P=0.000). Interestingly, μCi/g was negatively and positively correlated to the possibility of hormone increase and decrease, respectively. No significant differences were found in the other parameters assessed. At the early stage of I treatment for GD, few patients showed increased thyroid hormone levels. Key factors may include time of ATD discontinuation before I treatment and μCi/g. High μCi/g might decrease thyroid hormone levels in early treatment, making it safe.

Non-hyperfunctioning nodules from multinodular goiters: a minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsalpha subunit genes.

PubMed

Derrien, C; Sonnet, E; Gicquel, I; Le Gall, J Y; Poirier, J Y; David, V; Maugendre, D

2001-05-01

Constitutive activation of the cAMP pathway stimulates thyrocyte proliferation. Gain-of-function mutations in Gsalpha protein have already been identified in thyroid nodules which have lost the ability to trap iodine. In contrast, most of the studies failed to detect somatic activating mutations in the thyrotropin receptor (TSH-R) in non-hyperfunctioning thyroid tumors. The aim of this study was to screen for mutations TSH-R exon 10, encoding the whole intracytoplasmic area involved in signal transduction, and Gsalpha exons 8 and 9, containing the two hot-spot codons 201 and 227, in a subset of non-hyperfunctioning nodules from multinodular goiter. Identified by matching ultrasonography and scintiscan, 22 eufunctioning (normal 99Tc uptake) and 15 nonfunctioning (decreased 99Tc uptake) nodules from 27 non-toxic multinodular goiters were isolated. After DNA extraction, TSH-R exon 10 was analyzed by direct sequencing of the PCR products and Gsalpha exons 8 and 9 by Denaturing Gradient Gel Electrophoresis. No mutation of TSH-R or Gsalpha was detected in the 37 nodules analyzed. This absence of mutation, despite the use of two sensitive screening methods associated with the analysis of the TSH-R whole intracytoplasmic area and Gsalpha two hot-spot codons, suggests that TSH-R and Gsalpha play a minor role in the pathogenesis of non-toxic nodules from multinodular goiters.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortensen, Mary E., E-mail: MMortensen@cdc.gov; Birch, Rebecca; Wong, Lee-Yang

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO{sub 3}) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnantmore » women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO{sub 3}, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO{sub 3} on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001–2012. The geometric mean (GM) for urinary perchlorate was 4.04 µg/L, for TSH 1.46 mIU/L, and the arithmetic mean for FT4 1.11 ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO{sub 3} and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100 µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03 µg/L) were similar to pregnant women in NHANES (3.58 µg/L). - Highlights: • Limited biomonitoring data are available in pregnant women. • We found no effect of perchlorate and related anions on thyroid indicators in third trimester women. • Leafy green vegetables were a dietary source for perchlorate, nitrate, and thiocyanate.« less

Variations of rat thyroid activity during exposure to high environmental temperature (34 degrees C). Relation between hypothalamic pituitary and thyroid hormone levels.

PubMed

Rousset, B; Cure, M

1975-01-01

Changes in thyroid activity and variations in the hypthalamo-pituitary-thyroid hormone levels were examined in rats exposed to heat (34 degrees C)for3 weeks. Thyroid activity evaluated histologically (epithelium/colloid ratio, nuclear size) by radioiodine exploration (24 hrs 125 I uptake, ratio of mono- to di-125 iodotyrosines - MIT/DIT, ratio of tri- to tetra-125 iodothyronines-T3/T4, and plasma 125I-T4 and assay of plasma T4, evolves in a triphasic manner. 1.a depression phase between day 0 and day 2.5. 2. a rebound of thyroid activity between day 2.5 and day 9.3 a stabilization of thyroid parameters from day 9 to day 24. These results indicate adaptation of thyroid function to heat after 3 weeks. In phase i, plasma TSH )MeKenzie bioassay) fell to undectable levels concurrent with a 50% decrease in hypothalamic TRH (in vitro assay). Plasma TSH peaked on day 4.5, fell on day 9.5 and returned progressively to initial levels. Hypothalamic TRH returned to initial levels after 6.5 days. The rapid and simultaneous decrease in hypothalamic TRH, plasma TSH, plasma T4 and thyroid activity by the 36th hour of heat exposure (34 degrees C) suggests initiation at the hypothalamic level. In the secound phase, the rebound in thyroid activity is presumably due to the peak in circulating TSH in ralation to the marked decrease in plasma T4. The oscillations of phase 2 and the stabilization of all the thyroid parameters in phase 3 may be the reflection of an apparent discrepancy remains between a low plasma T4 and a normal or subnormal plasma TSH. A modification in the "set point" for the control of TSH secretion is discussed.

Developmental delay and failure to thrive in a 7-month-old baby boy with spontaneous transient Graves' thyrotoxicosis: a case report.

PubMed

Yatsuga, Shuichi; Saikusa, Tomoko; Sasaki, Takako; Ushijima, Kikumi; Kitamura, Miyuki; Nishioka, Junko; Koga, Yasutoshi

2016-08-10

Thyroid dysfunction can induce developmental delay and failure to thrive in infancy. Congenital hypothyroidism is one of the common causes of these symptoms in infancy. By contrast, hyperthyroidism is a rare cause of these symptoms in infancy. A 7-month-old Japanese baby boy was examined for developmental delay and failure to thrive. Blood tests were performed, which showed low levels of thyroid-stimulating hormone (<0.01 μU/mL) and high levels of free thyroxine (2.14 pg/mL). He was referred to our hospital at 8 months of age. His height was 64 cm (-2.7 standard deviation) and his weight was 6085 g (-2.5 standard deviation). No goiter was detected on examination. His thyrotropin receptor antibody was slightly high (3.9 IU/L), whereas thyroid stimulating antibody, anti-thyroglobulin antibody, and thyroid peroxidase antibody were within normal range. These blood findings indicated hyperthyroidism, most likely Graves' disease. His free thyroxine level decreased in the first month after our examination. No increased vascularity of his thyroid gland was noted. The technetium uptake of his thyroid gland in scintigraphy was relatively increased compared to the intake of his salivary gland. We elected to observe rather than treat with anti-thyroid medications. We have to rule out spontaneous transient Graves' thyrotoxicosis when babies have symptoms of developmental delay and fail to thrive.

Radioiodine thyroid remnant ablation after recombinant human thyrotropin or thyroid hormone withdrawal in patients with high-risk differentiated thyroid cancer.

PubMed

Pitoia, Fabián; Marlowe, Robert J; Abelleira, Erika; Faure, Eduardo N; Bueno, Fernanda; Schwarzstein, Diego; Lutfi, Rubén Julio; Niepomniszcze, Hugo

2012-01-01

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT

PubMed Central

Gao, Shun-Yu; Zhang, Xiao-Yan; Wei, Wei; Li, Xiao-Ting; Li, Yan-Ling; Xu, Min; Sun, Ying-Shi; Zhang, Xiao-Peng

2016-01-01

Abstract This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 ± 0.20 vs 1.17 ± 0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 ± 3.35 vs 3.46 ± 2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = –8.641 × unenhanced iodine concentration + 0.663 × iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y ≥ –2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions. PMID:27684811

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Śliwka, Przemysław W; Puła, Bartosz; Karwowski, Bolesław; Merecz-Sadowska, Anna; Dedecjus, Marek; Lewiński, Andrzej

2017-06-15

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131 I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131 I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations ( p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131 I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Electric and magnetic fields do not modify the biochemical properties of FRTL-5 cells.

PubMed

Dimida, A; Ferrarini, E; Agretti, P; De Marco, G; Grasso, L; Martinelli, M; Longo, I; Giulietti, D; Ricci, A; Galimberti, M; Siervo, B; Licitra, G; Francia, F; Pinchera, A; Vitti, P; Tonacchera, M

2011-03-01

Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described. The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL- 5). The experimental setup was designed in order to expose samples to a radiofrequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800-900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured. The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL- 5 cells with respect to basal conditions. In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro.

Biodistribution of I-123-iodo-amphetamine in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bischof-Delaloye, A.; HUngerbuhler, J.P.; Regli, F.

1984-01-01

Biodistribution and in vivo kinetics of iodo-amphetamine were studied in 18 patients (13 CVC, 3 metastases, 2 seizures). After 10 min of complete rest 5 mCi of N-isopropyl-p-(123I)-iodo-amphetamine(p,5n) were injected and 5, 15, 30, 45, 60, 90, 120 min blood samples taken. Whole body tracer distribution was studied with a dual head camera 30-60 and 90-120 min post-injection, at 24h in 3, at 48h in 2 patients. 3 days urinary elimination was measured in 2 patients. Brain, lung, liver, thyroid and bladder counts of anterior and posterior views were averaged and expressed as percent of WB activity. Brain ECT wasmore » performed 60 min p.i. in all, after 2h in 2 patients. Plasma activity decreased first with a fast, than with a slower component (mean Ti/2:5 and 60min respectively), than it became stable or increased slightly. 30-60min p.i. the brain concentrated an average of 5.6% of WB activity, the lungs 30.7%, the liver 19.2% and the thyroid 1%. Brain and thyroid activity did not significantly change during the second interval (6.3 and 1.1% respectively), lung activity decreased (24.7%), liver (22.7%) and bladder activity (1 to 2.3%) increased. 3 days urinary elimination was 6.3 and 7.9% of the injected dose respectively. In contrast with the findings in the primate no eye activity could be detected even at 24 and 48h. Intracerebral tracer distribution was similar on the 1 and 2h ECT. These data confirm the stability of brain activity observed in the animal between 30 and 120min after injection, but without showing any eye uptake of the tracer. Brain ECT with I-123-iodo-amphetamine may be performed during this interval under stable conditions in what concerns the absolute uptake as well as intracerebral distribution of the tracer.« less

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

PubMed

Ebihara, Itaru; Hirayama, Kouichi; Usui, Joichi; Seki, Masanori; Higuchi, Fujiko; Oteki, Takaaki; Kobayashi, Masaki; Yamagata, Kunihiro

2006-09-01

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

Endoplasmic reticulum stress inhibits expression of genes involved in thyroid hormone synthesis and their key transcriptional regulators in FRTL-5 thyrocytes

PubMed Central

Wen, Gaiping; Eder, Klaus

2017-01-01

Endoplasmic reticulum (ER) stress is characterized by the accumulation of misfolded proteins due to an impairment of ER quality control pathways leading to the activation of a defense system, called unfolded protein response (UPR). While thyrocytes are supposed to be highly susceptible to environmental conditions that cause ER stress due to the synthesis of large amounts of secretory proteins required for thyroid hormone synthesis, systematic investigations on the effect of ER stress on expression of key genes of thyroid hormone synthesis and their transcriptional regulators are lacking. Since the aim of the ER stress-induced UPR is to restore ER homeostasis and to facilitate cell survival through transient shutdown of ribosomal protein translation, we hypothesized that the expression of genes involved in thyroid hormone synthesis and their transcriptional regulators, all of which are not essential for cell survival, are down-regulated in thyrocytes during ER stress, while sterol regulatory element-binding proteins (SREBPs) are activated during ER stress in thyrocytes. Treatment of FRTL-5 thyrocytes with the ER stress inducer tunicamycin (TM) dose-dependently increased the mRNA and/or protein levels of known UPR target genes, stimulated phosphorylation of the ER stress sensor protein kinase RNA-like ER kinase (PERK) and of the PERK target protein eukaryotic initiation factor 2α (eIF2α) and caused splicing of the ER stress-sensitive transcription factor X-box binding protein (XBP-1) (P < 0.05). The mRNA levels and/or protein levels of genes involved in thyroid hormone synthesis, sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), their transcriptional regulators and thyrotropin (TSH) receptor and the uptake of Na125I were reduced at the highest concentration of TM tested (0.1 μg/mL; P < 0.05). Proteolytic activation of the SREBP-1c pathway was not observed in FRTL-5 cells treated with TM, whereas TM reduced proteolytic activation of the SREBP-2 pathway at 0.1 μg TM/mL (P < 0.05). In conclusion, the expression of key genes involved in thyroid hormone synthesis and their critical regulators and of the TSH receptor as well as the uptake of iodide is attenuated in thyrocytes during mild ER stress. Down-regulation of NIS, TPO and TG during ER stress is likely the consequence of impaired TSH/TSHR signaling in concert with reduced expression of critical transcriptional regulators of these genes. PMID:29095946

Endoplasmic reticulum stress inhibits expression of genes involved in thyroid hormone synthesis and their key transcriptional regulators in FRTL-5 thyrocytes.

PubMed

Wen, Gaiping; Ringseis, Robert; Eder, Klaus

2017-01-01

Endoplasmic reticulum (ER) stress is characterized by the accumulation of misfolded proteins due to an impairment of ER quality control pathways leading to the activation of a defense system, called unfolded protein response (UPR). While thyrocytes are supposed to be highly susceptible to environmental conditions that cause ER stress due to the synthesis of large amounts of secretory proteins required for thyroid hormone synthesis, systematic investigations on the effect of ER stress on expression of key genes of thyroid hormone synthesis and their transcriptional regulators are lacking. Since the aim of the ER stress-induced UPR is to restore ER homeostasis and to facilitate cell survival through transient shutdown of ribosomal protein translation, we hypothesized that the expression of genes involved in thyroid hormone synthesis and their transcriptional regulators, all of which are not essential for cell survival, are down-regulated in thyrocytes during ER stress, while sterol regulatory element-binding proteins (SREBPs) are activated during ER stress in thyrocytes. Treatment of FRTL-5 thyrocytes with the ER stress inducer tunicamycin (TM) dose-dependently increased the mRNA and/or protein levels of known UPR target genes, stimulated phosphorylation of the ER stress sensor protein kinase RNA-like ER kinase (PERK) and of the PERK target protein eukaryotic initiation factor 2α (eIF2α) and caused splicing of the ER stress-sensitive transcription factor X-box binding protein (XBP-1) (P < 0.05). The mRNA levels and/or protein levels of genes involved in thyroid hormone synthesis, sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), their transcriptional regulators and thyrotropin (TSH) receptor and the uptake of Na125I were reduced at the highest concentration of TM tested (0.1 μg/mL; P < 0.05). Proteolytic activation of the SREBP-1c pathway was not observed in FRTL-5 cells treated with TM, whereas TM reduced proteolytic activation of the SREBP-2 pathway at 0.1 μg TM/mL (P < 0.05). In conclusion, the expression of key genes involved in thyroid hormone synthesis and their critical regulators and of the TSH receptor as well as the uptake of iodide is attenuated in thyrocytes during mild ER stress. Down-regulation of NIS, TPO and TG during ER stress is likely the consequence of impaired TSH/TSHR signaling in concert with reduced expression of critical transcriptional regulators of these genes.

Etiological evaluation of primary congenital hypothyroidism cases.

PubMed

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-06-01

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice

PubMed Central

Neumann, Susanne; Huang, Wenwei; Titus, Steve; Krause, Gerd; Kleinau, Gunnar; Alberobello, Anna Teresa; Zheng, Wei; Southall, Noel T.; Inglese, James; Austin, Christopher P.; Celi, Francesco S.; Gavrilova, Oksana; Thomas, Craig J.; Raaka, Bruce M.; Gershengorn, Marvin C.

2009-01-01

Seven-transmembrane-spanning receptors (7TMRs) are prominent drug targets. However, small-molecule ligands for 7-transmembrane-spanning receptors for which the natural ligands are large, heterodimeric glycoprotein hormones, like thyroid-stimulating hormone (TSH; thyrotropin), have only recently been reported, and none are approved for human use. We have used quantitative high-throughput screening to identify a small-molecule TSH receptor (TSHR) agonist that was modified to produce a second agonist with increased potency. We show that these agonists are highly selective for human TSHR versus other glycoprotein hormone receptors and interact with the receptor's serpentine domain. A binding pocket within the transmembrane domain was defined by docking into a TSHR homology model and was supported by site-directed mutagenesis. In primary cultures of human thyrocytes, both TSH and the agonists increase mRNA levels for thyroglobulin, thyroperoxidase, sodium iodide symporter, and deiodinase type 2, and deiodinase type 2 enzyme activity. Moreover, oral administration of the agonist stimulated thyroid function in mice, resulting in increased serum thyroxine and thyroidal radioiodide uptake. Thus, we discovered a small molecule that activates human TSHR in vitro, is orally active in mice, and could be a lead for development of drugs to use in place of recombinant human TSH in patients with thyroid cancer. PMID:19592511

Comparison of Core-Needle Biopsy and Fine-Needle Aspiration for Evaluating Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: A Propensity Score Analysis.

PubMed

Suh, Chong Hyun; Choi, Young Jun; Lee, Jong Jin; Shim, Woo Hyun; Baek, Jung Hwan; Chung, Han Cheol; Shong, Young Kee; Song, Dong Eun; Sung, Tae Yon; Lee, Jeong Hyun

2017-10-01

This study used a propensity score analysis to assess the roles of core-needle biopsy (CNB) and fine-needle aspiration (FNA) in the evaluation of thyroid incidentalomas detected on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). The study population was obtained from a historical cohort who underwent 18 F-FDG PET/CT between October 2008 and September 2015. Patients were included who underwent ultrasound-guided CNB or FNA for incidental focal uptake of 18 F-FDG in the thyroid gland on PET/CT. The primary study outcomes included the inconclusive result rates in the CNB and FNA groups. The secondary outcome measures included the non-diagnostic result rate and the diagnostic performance for neoplasms. Multivariate analysis, propensity score matching, and inverse probability weighting were conducted. A total of 1360 nodules from 1338 patients were included in this study: 859 nodules from 850 patients underwent FNA, and 501 nodules from 488 patients underwent CNB. Compared to FNA, CNB demonstrated a significantly lower inconclusive result rate in the pooled cohort (23.8% vs. 35.4%; p < 0.001), propensity score-matched cohorts (22.9% vs. 36.6%; p < 0.001), and with inverse probability weighting (22.4% vs. 35.2%; p < 0.001). Non-diagnostic result rates were also significantly lower in CNB than in FNA. The diagnostic performance of the two groups in the pooled and matched cohorts was similar, with no significant differences found. The significantly lower inconclusive result rates in CNB than in FNA were consistent within the propensity score-matched cohorts. Therefore, CNB appears to be a promising diagnostic tool for patients with thyroid incidentalomas detected on 18 F-FDG PET/CT.

Primary goitrous hypothyroidism in a young adult domestic longhair cat: diagnosis and treatment monitoring

PubMed Central

Peterson, Mark E

2015-01-01

Case summary Primary goitrous hypothyroidism was diagnosed in a 12-month-old cat examined because of small stature, mental dullness, severe lethargy, generalized weakness and gait abnormalities. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of primary hypothyroidism was confirmed by low serum concentrations of total and free thyroxine (T4) with high thyroid-stimulating hormone (TSH) concentrations. Thyroid scintigraphy revealed severe enlargement of both thyroid lobes, as evidenced by a seven-fold increase in calculated thyroid volume above the reference interval. In addition, this bilateral goiter had an extremely high radionuclide uptake, about 10-fold higher than the normal feline thyroid gland. Treatment with twice-daily levothyroxine (L-T4), administered on an empty stomach, resulted in increased alertness, playfulness, strength and improvement in gait, as well as an increase in body length and weight. L-T4 replacement also led to normalization of serum thyroid hormone and TSH concentrations, and complete resolution of goiter. Relevance and novel information Spontaneous hypothyroidism is rarely reported in cats, with congenital hypothyroidism in kittens diagnosed most frequently. Despite the fact that this cat was a young adult, it likely had a form of congenital hypothyroidism caused by dyshormonogenesis (defect in thyroid hormone synthesis) that led to compensatory development of goiter. In hypothyroid cats, treatment with L-T4 is best given twice daily on an empty stomach to ensure adequate absorption. Normalization of serum TSH and shrinkage of goiter, as well as improvement in clinical signs, is the goal of treatment for cats with goitrous hypothyroidism. PMID:28491394

Primary goitrous hypothyroidism in a young adult domestic longhair cat: diagnosis and treatment monitoring.

PubMed

Peterson, Mark E

2015-01-01

Primary goitrous hypothyroidism was diagnosed in a 12-month-old cat examined because of small stature, mental dullness, severe lethargy, generalized weakness and gait abnormalities. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of primary hypothyroidism was confirmed by low serum concentrations of total and free thyroxine (T4) with high thyroid-stimulating hormone (TSH) concentrations. Thyroid scintigraphy revealed severe enlargement of both thyroid lobes, as evidenced by a seven-fold increase in calculated thyroid volume above the reference interval. In addition, this bilateral goiter had an extremely high radionuclide uptake, about 10-fold higher than the normal feline thyroid gland. Treatment with twice-daily levothyroxine (L-T4), administered on an empty stomach, resulted in increased alertness, playfulness, strength and improvement in gait, as well as an increase in body length and weight. L-T4 replacement also led to normalization of serum thyroid hormone and TSH concentrations, and complete resolution of goiter. Spontaneous hypothyroidism is rarely reported in cats, with congenital hypothyroidism in kittens diagnosed most frequently. Despite the fact that this cat was a young adult, it likely had a form of congenital hypothyroidism caused by dyshormonogenesis (defect in thyroid hormone synthesis) that led to compensatory development of goiter. In hypothyroid cats, treatment with L-T4 is best given twice daily on an empty stomach to ensure adequate absorption. Normalization of serum TSH and shrinkage of goiter, as well as improvement in clinical signs, is the goal of treatment for cats with goitrous hypothyroidism.

The effect of short-term treatment with lithium carbonate on the outcome of radioiodine therapy in patients with long-lasting Graves' hyperthyroidism.

PubMed

Sekulić, Vladan; Rajić, Milena; Vlajković, Marina; Ilić, Slobodan; Stević, Miloš; Kojić, Marko

2017-12-01

The outcome of radioiodine therapy (RIT) in Graves' hyperthyroidism (GH) mainly depends on radioiodine ( 131 I) uptake and the effective half-life of 131 I in the gland. Studies have shown that lithium carbonate (LiCO 3 ) enhances the 131 I half-life and increases the applied thyroid radiation dose without affecting the thyroid 131 I uptake. We investigated the effect of short-term treatment with LiCO 3 on the outcome of RIT in patients with long-lasting GH, its influence on the thyroid hormones levels 7 days after RIT, and possible side effects. Study prospectively included 30 patients treated with LiCO 3 and 131 I (RI-Li group) and 30 patients only with 131 I (RI group). Treatment with LiCO 3 (900 mg/day) started 1 day before RIT and continued 6 days after. Anti-thyroid drugs withdrawal was 7 days before RIT. Patients were followed up for 12 months. We defined a success of RIT as euthyroidism or hypothyroidism, and a failure as persistent hyperthyroidism. In RI-Li group, a serum level of Li was 0.571 ± 0.156 mmol/l before RIT. Serum levels of TT 4 and FT 4 increased while TSH decreased only in RI group 7 days after RIT. No toxic effects were noticed during LiCO 3 treatment. After 12 months, a success of RIT was 73.3% in RI and 90.0% in RI-Li group (P < 0.01). Hypothyroidism was achieved faster in RI-Li (1st month) than in RI group (3rd month). Euthyroidism slowly decreased in RI-Li group, and not all patients became hypothyroid for 12 months. In contrast, euthyroidism rapidly declined in RI group, and all cured patients became hypothyroid after 6 months. The short-term treatment with LiCO 3 as an adjunct to 131 I improves efficacy of RIT in patients with long-lasting GH. A success of RIT achieves faster in lithium-treated than in RI group. Treatment with LiCO 3 for 7 days prevents transient worsening of hyperthyroidism after RIT. Short-term use of LiCO 3 shows no toxic side effects.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

PubMed

Kagna, Olga; Pirmisashvili, Natalia; Tshori, Sagi; Freedman, Nanette; Israel, Ora; Krausz, Yodphat

2014-12-01

Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

131I activity quantification of gamma camera planar images.

PubMed

Barquero, Raquel; Garcia, Hugo P; Incio, Monica G; Minguez, Pablo; Cardenas, Alexander; Martínez, Daniel; Lassmann, Michael

2017-02-07

A procedure to estimate the activity in target tissues in patients during the therapeutic administration of 131 I radiopharmaceutical treatment for thyroid conditions (hyperthyroidism and differentiated thyroid cancer) using a gamma camera (GC) with a high energy (HE) collimator, is proposed. Planar images are acquired for lesions of different sizes r, and at different distances d, in two HE GC systems. Defining a region of interest (ROI) on the image of size r, total counts n g are measured. Sensitivity S (cps MBq -1 ) in each acquisition is estimated as the product of the geometric G and the intrinsic efficiency η 0 . The mean fluence of 364 keV photons arriving at the ROI per disintegration G, is calculated with the MCNPX code, simulating the entire GC and the HE collimator. Intrinsic efficiency η 0 is estimated from a calibration measurement of a plane reference source of 131 I in air. Values of G and S for two GC systems-Philips Skylight and Siemens e-cam-are calculated. The total range of possible sensitivity values in thyroidal imaging in the e-cam and skylight GC measure from 7 cps MBq -1 to 35 cps MBq -1 , and from 6 cps MBq -1 to 29 cps MBq -1 , respectively. These sensitivity values have been verified with the SIMIND code, with good agreement between them. The results have been validated with experimental measurements in air, and in a medium with scatter and attenuation. The counts in the ROI can be produced by direct, scatter and penetration photons. The fluence value for direct photons is constant for any r and d values, but scatter and penetration photons show different values related to specific r and d values, resulting in the large sensitivity differences found. The sensitivity in thyroidal GC planar imaging is strongly dependent on uptake size, and distance from the GC. An individual value for the acquisition sensitivity of each lesion can significantly alleviate the level of uncertainty in the measurement of thyroid uptake activity for each patient.

131I activity quantification of gamma camera planar images

NASA Astrophysics Data System (ADS)

Barquero, Raquel; Garcia, Hugo P.; Incio, Monica G.; Minguez, Pablo; Cardenas, Alexander; Martínez, Daniel; Lassmann, Michael

2017-02-01

A procedure to estimate the activity in target tissues in patients during the therapeutic administration of 131I radiopharmaceutical treatment for thyroid conditions (hyperthyroidism and differentiated thyroid cancer) using a gamma camera (GC) with a high energy (HE) collimator, is proposed. Planar images are acquired for lesions of different sizes r, and at different distances d, in two HE GC systems. Defining a region of interest (ROI) on the image of size r, total counts n g are measured. Sensitivity S (cps MBq-1) in each acquisition is estimated as the product of the geometric G and the intrinsic efficiency η 0. The mean fluence of 364 keV photons arriving at the ROI per disintegration G, is calculated with the MCNPX code, simulating the entire GC and the HE collimator. Intrinsic efficiency η 0 is estimated from a calibration measurement of a plane reference source of 131I in air. Values of G and S for two GC systems—Philips Skylight and Siemens e-cam—are calculated. The total range of possible sensitivity values in thyroidal imaging in the e-cam and skylight GC measure from 7 cps MBq-1 to 35 cps MBq-1, and from 6 cps MBq-1 to 29 cps MBq-1, respectively. These sensitivity values have been verified with the SIMIND code, with good agreement between them. The results have been validated with experimental measurements in air, and in a medium with scatter and attenuation. The counts in the ROI can be produced by direct, scatter and penetration photons. The fluence value for direct photons is constant for any r and d values, but scatter and penetration photons show different values related to specific r and d values, resulting in the large sensitivity differences found. The sensitivity in thyroidal GC planar imaging is strongly dependent on uptake size, and distance from the GC. An individual value for the acquisition sensitivity of each lesion can significantly alleviate the level of uncertainty in the measurement of thyroid uptake activity for each patient.

Hyperthyroidism increases brown fat metabolism in humans.

PubMed

Lahesmaa, Minna; Orava, Janne; Schalin-Jäntti, Camilla; Soinio, Minna; Hannukainen, Jarna C; Noponen, Tommi; Kirjavainen, Anna; Iida, Hidehiro; Kudomi, Nobuyuki; Enerbäck, Sven; Virtanen, Kirsi A; Nuutila, Pirjo

2014-01-01

Thyroid hormones are important regulators of brown adipose tissue (BAT) development and function. In rodents, BAT metabolism is up-regulated by thyroid hormones. The purpose of this article was to investigate the impact of hyperthyroidism on BAT metabolism in humans. This was a follow-up study using positron emission tomography imaging. Glucose uptake (GU) and perfusion of BAT, white adipose tissue, skeletal muscle, and thyroid gland were measured using [18F]2-fluoro-2-deoxy-D-glucose and [15O]H2O and positron emission tomography in 10 patients with overt hyperthyroidism and in 8 healthy participants. Five of the hyperthyroid patients were restudied after restoration of euthyroidism. Supraclavicular BAT was quantified with magnetic resonance imaging or computed tomography and energy expenditure (EE) with indirect calorimetry. Compared with healthy participants, hyperthyroid participants had 3-fold higher BAT GU (2.7±2.3 vs 0.9±0.1 μmol/100 g/min, P=.0013), 90% higher skeletal muscle GU (P<.005), 45% higher EE (P<.005), and a 70% higher lipid oxidation rate (P=.001). These changes were reversible after restoration of euthyroidism. During hyperthyroidism, serum free T4 and free T3 were strongly associated with EE and lipid oxidation rates (P<.001). TSH correlated inversely with BAT and skeletal muscle glucose metabolism (P<.001). Hyperthyroidism had no effect on BAT perfusion, whereas it stimulated skeletal muscle perfusion (P=.04). Thyroid gland GU did not differ between hyperthyroid and euthyroid study subjects. Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates.

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

Clinical experience with recombinant human thyroid-stimulating hormone (rhTSH): whole-body scanning with iodine-131.

PubMed

Reiners, C; Luster, M; Lassmann, M

1999-01-01

Whole-body scanning (WBS) with iodine-131 (I-131) is currently used together with serum thyroglobulin (Tg) measurement in the diagnostic follow-up of well-differentiated thyroid carcinoma. One of the main disadvantages of I-131 WBS is its requirement of repeated weeks-long withdrawal of thyroid hormone suppression therapy (THST) to raise endogenous thyroid-stimulating hormone (TSH) production. This results in hypothyroidism and associated abnormalities, discomfort and morbidity. Recently, however, a series of multicentre clinical studies established the efficacy, safety, non-antigenicity, and quality of life benefits of recombinant human TSH (rhTSH, Thyrogen, thyrotropin alfa, Genzyme Corporation, Cambridge, MA, USA) in promoting radioiodine uptake and permitting sensitive I-131 WBS in patients on THST after initial therapy of well-differentiated thyroid cancer. Thus in everyday practice, rhTSH administration may in many cases supersede THST withdrawal as a preparative method for I-131 imaging. With the use of rhTSH, as whenever I-131 WBS is performed, useful and accurate imaging requires meticulous attention to good scanning practices. These include use of appropriate equipment, proper timing, sufficient scanning time, vigilance against artifacts and iodine contamination, and consideration of additional imaging in the case of ambiguous 48-hour scans. Whole-body retention of I-131 is approximately 50% greater during hypothyroidism after THST withdrawal than during euthyroidism on THST and rhTSH. Therefore, it is important to use an adequate diagnostic activity of > or =4 mCi (148 MBq) to compensate for the faster radioiodine clearance in the euthyroid state permitted by rhTSH administration. Ongoing dosimetric research eventually may provide more specific guidance regarding radioiodine activities for diagnostic, and, particularly, therapeutic purposes, with the use of rhTSH.

The presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) does not exclude the diagnosis of type 2 amiodarone-induced thyrotoxicosis.

PubMed

Tomisti, L; Urbani, C; Rossi, G; Latrofa, F; Sardella, C; Manetti, L; Lupi, I; Marcocci, C; Bartalena, L; Curzio, O; Martino, E; Bogazzi, F

2016-05-01

It is widely accepted that type 2 amiodarone-induced thyrotoxicosis (AIT) generally occurs in patients with a normal thyroid gland without signs of thyroid autoimmunity. However, it is currently unknown if the presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) in AIT patients without other signs of an underlying thyroid disease may impair the response to glucocorticoid therapy. We performed a pilot retrospective cohort study with matched-subject design and an equivalence hypothesis, comparing the response to glucocorticoid therapy between 20 AIT patients with a normal thyroid gland, low radioiodine uptake, undetectable TSH receptor antibodies and positive TgAb and/or TPOAb (Ab+ group), and 40 patients with the same features and absent thyroid antibodies (Ab- group). The mean cure time was 54 ± 68 days in the Ab+ group and 55 ± 49 days in the Ab- group (p = 0.63). The equivalence test revealed an equivalent cure rate after 60, 90 and 180 days (p = 0.67, 0.88 and 0.278, respectively). The occurrence of permanent hypothyroidism was higher in the Ab+ group than in the Ab- group (26.3 vs 5.13 %, p = 0.032). The presence of TgAb and/or TPOAb does not affect the response to glucocorticoid therapy, suggesting that the patients with features of destructive form of AIT should be considered as having a type 2 AIT irrespective of the presence of TGAb or TPOAb. These patients have a higher risk of developing hypothyroidism after the resolution of thyrotoxicosis and should be monitored accordingly.

The Na+/I− Symporter (NIS): Mechanism and Medical Impact

PubMed Central

Portulano, Carla; Paroder-Belenitsky, Monika

2014-01-01

The Na+/I− symporter (NIS) is the plasma membrane glycoprotein that mediates active I− transport in the thyroid and other tissues, such as salivary glands, stomach, lactating breast, and small intestine. In the thyroid, NIS-mediated I− uptake plays a key role as the first step in the biosynthesis of the thyroid hormones, of which iodine is an essential constituent. These hormones are crucial for the development of the central nervous system and the lungs in the fetus and the newborn and for intermediary metabolism at all ages. Since the cloning of NIS in 1996, NIS research has become a major field of inquiry, with considerable impact on many basic and translational areas. In this article, we review the most recent findings on NIS, I− homeostasis, and related topics and place them in historical context. Among many other issues, we discuss the current outlook on iodide deficiency disorders, the present stage of understanding of the structure/function properties of NIS, information gleaned from the characterization of I− transport deficiency-causing NIS mutations, insights derived from the newly reported crystal structures of prokaryotic transporters and 3-dimensional homology modeling, and the novel discovery that NIS transports different substrates with different stoichiometries. A review of NIS regulatory mechanisms is provided, including a newly discovered one involving a K+ channel that is required for NIS function in the thyroid. We also cover current and potential clinical applications of NIS, such as its central role in the treatment of thyroid cancer, its promising use as a reporter gene in imaging and diagnostic procedures, and the latest studies on NIS gene transfer aimed at extending radioiodide treatment to extrathyroidal cancers, including those involving specially engineered NIS molecules. PMID:24311738

Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma.

PubMed

Reiners, Christoph; Biko, Johannes; Haenscheid, Heribert; Hebestreit, Helge; Kirinjuk, Stalina; Baranowski, Oleg; Marlowe, Robert J; Demidchik, Ewgeni; Drozd, Valentina; Demidchik, Yuri

2013-07-01

After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. Outcomes were response to therapy and disease status, mortality, and treatment toxicity. Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 μg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 μg/L), and 11 (4.8%) had partial remission (Tg > 10 μg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

PubMed

Reinhardt, Michael J; Brink, Ingo; Joe, Alexius Y; Von Mallek, Dirk; Ezziddin, Samer; Palmedo, Holger; Krause, Thomas M

2002-09-01

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.

Interaction of interferon alpha therapy with thyroid function tests in the management of hepatitis C: a case report.

PubMed

Gill, Gurmit; Bajwa, Hammad; Strouhal, Peter; Buch, Harit N

2016-09-15

Interferon alpha is a widely used therapeutic agent in the treatment of hepatitis C virus infection. Clinical thyroid disease is seen in nearly 15 % of patients receiving interferon alpha for hepatitis C virus infection. The mechanism of thyroid dysfunction with interferon alpha is either autoimmune or inflammatory. We report a case of young woman who developed biphasic thyroid dysfunction posing a diagnostic challenge, while receiving interferon alpha treatment for hepatitis C virus infection. A 29-year-old, Caucasian woman with type 1 diabetes and hepatitis C virus infection was referred with hyperthyroidism, while she was at 17 weeks of a planned 24-week course of interferon alpha therapy. A laboratory investigation revealed a thyroid stimulation hormone level of 0.005 mU/L (0.350-4.94), free thyroxine of 45.6 pmol/L (9.0-19.0) and free tri-iodothyronine of 12.6 pmol/L (2.6-5.7). She had a mild neutropenia and alanine aminotransferase at double the reference value. Her thyroid peroxidase antibody level was 497 ku/L (<5.6) and thyroid inhibitory factor 7 IU/L (>1.8 iu/l is positive). Thyroid scintigraphy with technetium99 scan confirmed a normal-sized thyroid gland with diffuse but normal overall uptake. A diagnosis of interferon alpha-triggered autoimmune hyperthyroidism as opposed to an inflammatory thyroiditis was made. She was offered radioactive iodine therapy, as thionamides were considered inappropriate in view of her liver disease and mild neutropenia. Due to our patient's personal circumstances, radioactive iodine therapy was delayed by 8 weeks and her thyrotoxic symptoms were controlled with beta-blockers alone. A repeat thyroid function test, 4 weeks post treatment with interferon alpha, indicated spontaneous conversion to hypothyroidism with a thyroid stimulation hormone level of 100 mU/L, free thyroxine of 5.2 pmol/L and free tri-iodothyronine of 1.7 pmol/L. She subsequently received levothyroxine for 4 months only and had remained euthyroid for the last 3 months without any treatment. Initial investigations favored the autoimmune nature of hyperthyroidism but follow-up of the case, interestingly, was more consistent with inflammatory thyroiditis. We propose that this can be explained either on the basis of autoimmune subacute thyroiditis or a change in the nature of thyroid stimulation hormone receptor antibody production from stimulating-type to blocking-type antibodies, with disappearance of the latter on discontinuation of interferon alpha.

Hyperfunctioning thyroid nodules in children and adolescents.

PubMed

de Luca, F; Chaussain, J L; Job, J C

1986-01-01

Eight children and adolescents, seven female and one male, aged 7.1 to 15.0 years, referred over a 12-year period for a solitary mass in an otherwise normal thyroid gland, exhibited a hyperfunctioning nodule on thyroid scintiscan. Tracer uptake in the surrounding thyroid tissue was reduced or completely suppressed, but could be restored after TSH stimulation. Only one patient had mild clinical hyperthyroidism with normal T4 but increased T3 serum levels and blunted TSH responsiveness to TRH. A similar hormonal pattern suggestive of subclinical hyperthyroidism was found in three other subjects who were clinically euthyroid. One patient initially euthyroid progressed to subclinical hyperthyroidism two years later. In the whole group a significant negative relationship was found between serum T3 level and TRH-stimulated TSH peak (r = -0.829, p less than 0.02). All the patients underwent selective surgery after a 3-month to 2-year period of follow-up. Microscopic examination was consistent with adenoma in seven patients, while in one case a well-encapsulated papillary adenocarcinoma was found. Though hyperfunctioning nodules are seldom malignant, their surgical removal must be recommended when they become thyrotoxic, exceed 3 cm or show progressive enlargement.

Radioiodine Accumulation in a Giant Ovarian Cystadenofibroma Detected Incidentally by 131-I Whole Body Scans

PubMed Central

Mebarki, Mohammed; Menemani, Abdelghani; Medjahedi, Abdelkader; Boualou, Fouad; Slama, Abdelhak; Ouguirti, Sarah; Kherbouche, Fatima Zahra; Berber, Nécib

2012-01-01

Ovarian cystadenofibroma is a relatively rare tumor; it is usually asymptomatic and is found incidentally. We present the case of a 24-year-old female patient, who had undergone total thyroidectomy for thyroid papillary carcinoma, with an asymptomatic giant cystadenofibroma, incidentally discovered by diagnostic 131I-SPECT/CT WBSs. We summarize the clinical history, imaging data, and histopathological study on a rare case of radioiodine accumulation in cystadenofibroma, and we discuss the mechanism of uptake of radioiodine in this case. PMID:23119215

The limit of detection in scintigraphic imaging with I-131 in patients with differentiated thyroid carcinoma

NASA Astrophysics Data System (ADS)

Hänscheid, H.; Lassmann, M.; Buck, A. K.; Reiners, C.; Verburg, F. A.

2014-05-01

Radioiodine scintigraphy influences staging and treatment in patients with differentiated thyroid carcinoma. The limit of detection for fractional uptake in an iodine avid focus in a scintigraphic image was determined from the number of lesion net counts and the count density of the tissue background. The count statistics were used to calculate the diagnostic activity required to elevate the signal from a lesion with a given uptake significantly above a homogeneous background with randomly distributed counts per area. The dependences of the minimal uptake and the minimal size of lesions visible in a scan on several parameters of influence were determined by linking the typical biokinetics observed in iodine avid tissue to the lesion mass and to the absorbed dose received in a radioiodine therapy. The detection limits for fractional uptake in a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq, 0.01% for activities typically administered in diagnostic assessments (74-185 MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of detection in a diagnostic scan with biokinetics eligible for radioiodine therapy are small with diameters of a few millimeters. Increasing the diagnostic activity by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm. Several other determinants have a comparable or higher influence on the limit of detection than the administered activity; most important are the biokinetics in both blood pool and target tissue and the time of measurement. A generally valid recommendation for the timing of the scan is impossible as the time of the highest probability to detect iodine avid tissue depends on the administered activity as well as on the biokinetics in the lesion and background in the individual patient.

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome

PubMed Central

Zhang, Guangjian; Gao, Rui; Wang, Yuanbo; Liu, Yan; Li, Juan; Jia, Xi; Liang, Yiqian; Yang, Aimin

2018-01-01

Aims To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake. PMID:29423055

Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma.

PubMed

Shakir, Mohamed K M; Krook, Linda S; Schraml, Frank V; Hays, James H; Clyde, Patrick W

2008-07-01

Strategies to improve I131 uptake in thyroid carcinoma include levothyroxine (LT4) withdrawal or thyrotropin (TSH) administration along with a low-iodine diet. We report five patients with papillary or follicular thyroid carcinoma who developed symptomatic hyponatremia during LT4 withdrawal and low-iodine diet. Four patients had pulmonary and/or brain metastases. All had restricted iodine intakes during LT4 withdrawal. Presenting complaints included weakness, dizziness, fainting spells, lethargy, and/or nausea. Baseline serum sodium levels while on LT4 suppression were normal. During presentation all were hypothyroid and serum sodium ranged from 110 to 121 mmol/L (normal 135-148). Despite hyponatremia, the plasma renin activity and serum aldosterone levels were suppressed, indicating volume expansion. The hyponatremia responded to fluid restriction and normalized after LT4 replacement. Low sodium intake, inappropriate antidiuretic hormone secretion syndrome (SIADH)-like disorder secondary to hypothyroidism and/or lung or cerebral metastases may have contributed to hyponatremia. The development of hyponatremia during LT4 withdrawal and low-iodine diet in otherwise healthy patients with thyroid carcinoma is extremely rare. However, elderly patients with metastatic thyroid carcinoma need observation during LT4 withdrawal combined with a low-iodine diet and should receive instruction to take iodine-free sodium chloride. Free water restriction may be necessary in some patients.

Tiratricol-induced periodic paralysis: a review of nutraceuticals affecting thyroid function.

PubMed

Cohen-Lehman, Janna; Charitou, Marina M; Klein, Irwin

2011-01-01

To review the potential adverse effects of thyroid hormone-based nutraceuticals and describe a case of thyrotoxic periodic paralysis (TPP) after abuse of a dietary supplement containing 3,5,3'-triiodothyroacetic acid (tiratricol). We review the literature on potential dangers and therapeutic misadventures of thyroid hormone-based nutraceuticals and present the clinical, laboratory, and radiologic data of a bodybuilder in whom hypokalemic TPP developed after use of "Triax Metabolic Accelerator". A 23-year-old white man developed lower extremity paralysis, diaphoresis, and palpitations in the setting of low serum potassium levels. Laboratory results showed suppressed thyroid-stimulating hormone, low levels of free and total thyroxine, low total triiodothyronine level, and very low 24-hour radioiodine uptake. The patient ultimately admitted to taking a supplement containing tiratricol for approximately 2 months, and hypokalemic TPP was diagnosed. He was treated with potassium supplementation and a β-adrenergic blocking agent, which completely resolved his symptoms. Results of thyroid function tests normalized or approached normal 1 week after hospitalization, and future use of dietary supplements was strongly discouraged. Despite 2 warnings by the US Food and Drug Administration, products containing tiratricol are still available for sale on the Internet. This report illustrates both an unusual adverse effect of a nutraceutical containing tiratricol and the importance of educating our patients about the risks versus benefits of using these widely available but loosely regulated products.

Congenital dyshormonogenic hypothyroidism with goiter caused by a sodium/iodide symporter (SLC5A5) mutation in a family of Shih-Tzu dogs.

PubMed

Soler Arias, E A; Castillo, V A; Garcia, J D; Fyfe, J C

2018-04-24

An iodide transport defect (ITD) in the thyroid gland was determined to cause congenital dyshormonogenic hypothyroidism with goiter (CDHG) in 2 members of a family of Shih-Tzu dogs. Strikingly, both dogs were also diagnosed with dilated cardiomyopathy at 24 and 1.5 mo of age. The only sign of hypothyroidism was a moderate growth delay in the adult dog. The ITD was recognized by the absence of uptake of technetium-99m in the salivary glands (sg) and goiter observed by scintigraphy. In the same scan, radiopharmaceutical uptake was found in the anterior mediastinum of both dogs and in the right axillary lymph node in the oldest dog. A follicular thyroid carcinoma was diagnosed by histopathology after thyroidectomy of the older dog. An adenomatous goiter with ectopic thyroid tissue, and degenerative changes in myocardium were the findings after necropsy in the youngest dog. A homozygous mutation of the intron 9 splice acceptor site of SLC5A5 gene, encoding the sodium/iodine symporter (NIS), was found in the DNA of one of the affected dogs. The mutation was a single base transition of guanine > adenine (G > A) at position 45,024,672 of dog chromosome 20 (CFA20). Five of eight healthy dogs, including both parents of one of the dogs exhibiting CDHG, were heterozygous A/G, and the other 3 were homozygous for the wild-type allele G/G. No sequence variant was found in thyroid peroxidase of the affected dog. Congenital dyshormonogenic hypothyroidism with goiter in this family is an autosomal recessive trait. Our findings are the first evidence of an SLC5A5 mutation in dogs and establish a new genetic cause of CDHG. Copyright © 2018 Elsevier Inc. All rights reserved.

An evaluation of the value of first thyroglobulin determination in the diagnostics of metastases immediately following differentiated thyroid carcinoma surgery.

PubMed

Makarewicz, Jacek; Adamczewski, Zbigniew; Rutkowski, Antoni; Mikosiński, Sławomir; Knapska-Kucharska, Małgorzata; Gonerska-Szadkowska, Anna; Oszukowska, Lidia; Karwowska, Anzelmina; Lewiński, Andrzej

2006-01-01

Evaluation of the differential value of the first thyroglobulin (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of either metastases or residual cancer (M). Data from 517 patients with DTC after Tx, with follow-up > 1.5 year were analysed retrospectively. Patients in whom either the course of the disease was unclear or interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were excluded from the study. Finally, the data from 247 patients were evaluated (age: 14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group M1; n = 35) were compared with the same parameters in patients with remission > 1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The clinical decision limit of Tg level to be suggestive of metastases was determined by means of efficiency curve. Groups M0 and M1 did not differ from each other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p = 0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). First thyroglobulin concentration, determined after thyroidectomy but before other treatment, is higher in patients with metastatic DTC than in patients without such metastases. This indicates that Tg level may be used as an early marker of either residual or metastatic DTC (even if thyroid remnants are present).

Development of a terrestrial vertebrate model for assessing bioavailability of cadmium in the fence lizard (Sceloporus undulatus) and in ovo effects on hatchling size and thyroid function.

PubMed

Brasfield, Sandra M; Bradham, Karen; Wells, Jason B; Talent, Larry G; Lanno, Roman P; Janz, David M

2004-03-01

In the terrestrial environment, standardized protocols are available for measuring the exposure and effects of contaminants to invertebrates, but none currently exist for vertebrates. In an effort to address this, we proposed that developing lizard embryos may be used as a terrestrial vertebrate model. Lizard eggs may be particularly susceptible to soil contamination and in ovo exposure may affect hatchling size, mortality, as well as thyroid function. Toxicant-induced perturbations of thyroid function resulting from in ovo chemical exposure may result in toxicity during the critical perinatal period in reptiles. Fertilized Eastern fence lizard (Sceloporus undulatus) eggs were placed in cadmium (Cd)-spiked expanded perlite (0, 1.48, 14.8, 148, 1480, 14,800 microg Cd/g, nominal concentrations), artificially incubated at 28 degrees C, and examined daily for mortality. Whole lizard hatchlings as well as failed hatches were homogenized in ethanol and the homogenate was divided for Cd body residue analysis and thyroid hormone (triiodothyronine (T3) and thyroxine (T4)) analyses. Acute mortality was observed in the two highest doses (1480 and 14800 microg Cd/g). Cadmium body residues showed a higher internal concentration with increasing exposure concentration indicating uptake of Cd. There was a decrease in T3:T4 ratio at the highest surviving dose (148 microg Cd/g), however, there were no differences observed in hatchling size measured as weight and snout-vent length, or in whole body thyroid hormone levels. In summary, this study has shown Cd amended to a solid phase representing soil (perlite) can traverse the thin, parchment-like shell membrane of the fence lizard egg and bioaccumulate in lizard embryos. We believe this study is a good first step in investigating and evaluating this species for use as a model.

Improvement of Cerebral Hypoperfusion with Levothyroxine Therapy in Hashimoto's Encephalopathy Demonstrated by 99mTc-HMPAO-SPECT

PubMed Central

Schnedl, Wolfgang J.; Mirzaei, Siroos; Wallner-Liebmann, Sandra J.; Tafeit, Erwin; Mangge, Harald; Krause, Robert; Lipp, Rainer W.

2013-01-01

Background Hashimoto's encephalopathy (HE) is a rare immune-mediated encephalopathy associated with autoimmune Hashimoto's thyroiditis. Objectives and Methods We report on a patient with HE and significant clinical improvement correlating with an increase in cerebral blood flow demonstrated by hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). HMPAO-SPECT was performed with 740 MBq of technetium-99m-HMPAO. To demonstrate the improvement in regional cerebral blood flow, individual regions of interest were drawn around visually diminished HMPAO uptake, the lesion to reference region ratio was calculated and transverse section images and semi-quantitative measurements were performed. Results We show a 5-year follow-up with significant clinical improvement, a 10-fold reduction in autoantibodies to thyroid peroxidase and an approximately 20% improvement in cerebral blood flow with HMPAO-SPECT. Conclusion Adequate levothyroxine treatment achieving and maintaining euthyroidism should be considered as therapy to lower autoantibodies and improve clinical outcome in patients with Hashimoto's thyroiditis and encephalopathy. PMID:24783049

Radioiodine-induced hypothyroidism in Graves' disease: factors associated with the increasing incidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunnien, A.J.; Hy, I.D.; Gorman, C.A.

1982-11-01

A retrospective analysis was done of the records of 454 patients who received their first I-131 treatment for Graves' disease during six periods covering 1951 to 1978. In the earliest group, 3% of patients were hypothyroid 3 mo after I-131 use, and 40% were hypothyroid at 1 yr. In the most recent group, 36% of patients were hypothyroid at 3 mo and 91% were myxedematous at 1 yr. Although no obvious trends were noted, whether in the number of patients pretreated with thionamide drugs, in the mean 24-hr I-131 uptake, or in the calculated dose of I-131 (..mu..Ci/estimated gram ofmore » thyroid tissue) during the years of the study, the initial mean dose of I-131 administered increased from 8.1 mCi in the earliest group to 13.8 mCi in the latest group. Concurrently, estimates of gland size increased from a mean of 26 g in the first group to 43 g in the last. If, in patients with Graves' disease, the thyroid gland size did not truly increase during the years of the study, the increasing occurrence of early hypothyroidism seen after I-131 use may reflect the conscious or unconscious decision to use larger doses of I-131 calculated on the basis of inflated estimates of thyroid gland weight.« less

Radioiodine-induced hypothyroidism in Graves' disease: factors associated

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunnien, A.J.; Hay, I.D.; Gorman, C.A.

1982-11-01

A retrospective analysis was done of the records of 454 patients who received their first /sup 131/I treatment for Graves' disease during six periods covering 1951 to 1978. In the earliest group, 3% of patients were hypothyroid 3 mo after /sup 131/I use, and 40% were hypothyroid at 1 yr. In the most recent group, 36% of patients were hypothyroid at 3 mo and 91% were myxedematous at 1 yr. Although no obvious trends were noted, whether in the number of patients pretreated with thionamide drugs, in the mean 24-hr /sup 131/I uptake, or in the calculated dose of /supmore » 131/I (muCi/estimated gram of thyroid tissue) during the years of the study, the initial mean dose of /sup 131/I administered increased from 8.1 mCi in the earliest group to 13.8 mCi in the latest group. Concurrently, estimates of gland size increased from a mean of 26 g in the first group to 43 g in the last. If, in patients with Graves' disease, the thyroid gland size did not truly increase during the years of the study, the increasing occurrence of early hypothyroidism seen after /sup 131/I use may reflect the conscious or unconscious decision to use larger doses of /sup 131/I calculated on the basis of inflated estimates of thyroid gland weight.« less

External Beam Radiation in Differentiated Thyroid Carcinoma

PubMed Central

Billan, Salem; Charas, Tomer

2016-01-01

The treatment of differentiated thyroid carcinoma (DTC) is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI). External beam radiotherapy (EBRT) is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient’s age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco-regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT. PMID:26886956

Etiological evaluation of primary congenital hypothyroidism cases

PubMed Central

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-01-01

Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Conclusions Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism. PMID:28747839

Pituitary Adenoma Recurrence Suspected on Central Hyperthyroidism Despite Empty Sella and Confirmed by 68Ga-DOTA-TOC PET/CT.

PubMed

Gauthé, Mathieu; Sarfati, Julie; Bourcigaux, Nathalie; Christin-Maitre, Sophie; Talbot, Jean-Noël; Montravers, Françoise

2017-06-01

Thyrotropin-secreting pituitary adenomas are very rare tumors, known to present overexpression of somatostatin receptor subtype 2 and which may consequently demonstrate abnormal uptake on Ga-DOTA-TOC PET/CT. A 67-year-old woman with a history of operated pituitary macroadenoma presented with symptoms of hyperthyroidism including a large goiter. Her serum thyroid hormone levels were in favor of central hyperthyroidism. Pituitary MRI depicted an empty sella but visualized an ambiguous lesion centered on the left sphenoidal sinus. Complementary Ga-DOTA-TOC PET/CT finally demonstrated intense uptake by the sphenoidal lesion, confirming recurrence of the pituitary adenoma.

Selective capture of iodide from solutions by microrosette-like δ-Bi₂O₃.

PubMed

Liu, Long; Liu, Wei; Zhao, Xiaoliang; Chen, Daimei; Cai, Rongsheng; Yang, Weiyou; Komarneni, Sridhar; Yang, Dongjiang

2014-09-24

Radioactive iodine isotopes that are produced in nuclear power plants and used in medical research institutes could be a serious threat to the health of many people if accidentally released to the environment because the thyroid gland can absorb and concentrate them from a liquid. For this reason, uptake of iodide anions was investigated on microrosette-like δ-Bi2O3 (MR-δ-Bi2O3). The MR-δ-Bi2O3 adsorbent showed a very high uptake capacity of 1.44 mmol g(-1) by forming insoluble Bi4I2O5 phase. The MR-δ-Bi2O3 also displayed fast uptake kinetics and could be easily separated from a liquid after use because of its novel morphology. In addition, the adsorbent showed excellent selectivity for I(-) anions in the presence of large concentrations of competitive anions such as Cl(-) and CO3(2-), and could work in a wide pH range of 4-11. This study led to a new and highly efficient Bi-based adsorbent for iodide capture from solutions.

Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat.

PubMed

Fernandez, M; Pirondi, S; Manservigi, M; Giardino, L; Calzà, L

2004-10-01

Oligodendrocyte development and myelination are under thyroid hormone control. In this study we analysed the effects of chronic manipulation of thyroid status on the expression of a wide spectrum of oligodendrocyte precursor cells (OPCs) markers and myelin basic protein (MBP) in the subventricular zone (SVZ), olfactory bulb and optic nerve, and on neural stem cell (NSC) lineage in adult rats. Hypo- and hyperthyroidism were induced in male rats, by propyl-thio-uracil (PTU) and L-thyroxin (T4) treatment, respectively. Hypothyroidism increased and hyperthyroidism downregulated proliferation in the SVZ and olfactory bulb (Ki67 immunohistochemistry and Western blotting, bromodeoxyuridine uptake). Platelet-derived growth factor receptor alpha (PDGFalpha-R) and MBP mRNA levels decreased in the optic nerve of hypothyroid rats; the same also occurred at the level of MBP protein. Hyperthyroidism slightly upregulates selected markers such as NG2 in the olfactory bulb. The lineage of cells derived from primary cultures of NSC prepared from the forebrain of adult hypo- and hyperthyroid also differs from those derived from control animals. Although no difference of in vitro proliferation of NSCs was observed in the presence of epidermal growth factor, maturation of oligodendrocytes (defined by process number and length) was enhanced in hyperthyroidism, suggesting a more mature state than in control animals. This difference was even greater when compared with the hypothyroid group, the morphology of which suggested a delay in differentiation. These results indicate that thyroid hormone affects NSC and OPC proliferation and maturation also in adulthood.

Alteration of thyroid hormone concentrations in juvenile Chinook salmon (Oncorhynchus tshawytscha) exposed to polybrominated diphenyl ethers, BDE-47 and BDE-99.

PubMed

Arkoosh, Mary R; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Dietrich, Joseph P

2017-03-01

Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) and BDE-99 (2,2',4,4',5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3-552 ng total PBDEs/g food), BDE-99 (0.3-580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7-690 ng total PBDEs/g food) for 39-40 days. The concentrations of circulating total thyroid hormones, thyroxine (T 4 ) and 3,5,3'-triiodothyronine (T 3 ), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T 4 and T 3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T 3 or T 4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T 3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes. Published by Elsevier Ltd.

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

PubMed Central

Gilbert, Mary E.; Sui, Li

2008-01-01

Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

(131)I-Nimotuzumab - A potential radioimmunotherapeutic agent in treatment of tumors expressing EGFR.

PubMed

Kameswaran, Mythili; Samuel, Grace; Dev Sarma, Haladhar; Shinde, Swamirao N; Dash, Ashutosh; Venkatesh, Meera

2015-08-01

The anti-EGFR antibody Nimotuzumab was radioiodinated with I-131 by Chloramine T and Iodogen methods. The (131)I-Nimotuzumab was purified and characterized by HPLC. Purified (131)I-Nimotuzumab exhibited radiochemical purity of >95% and retained good in vitro stability upto 24h at room temperature by both the methods. Cell binding studies carried out in A431 cells expressing EGF receptors showed good immunoreactivity of the product upto 5 days post radioiodination. Biodistribution studies in normal Swiss mice showed fast clearance by both renal and gastrointestinal routes with minimal thyroid uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

Do Thyroxine and Thyroid-Stimulating Hormone Levels Reflect Urinary Iodine Concentrations?

PubMed Central

Soldin, Offie P.; Tractenberg, Rochelle E.; Pezzullo, John C.

2013-01-01

The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an ‘‘iodine-sufficient population.’’ Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988–1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15–44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status. PMID:15795649

Amiodarone-induced thyrotoxicosis: A review

PubMed Central

Tsang, Wendy; Houlden, Robyn L

2009-01-01

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) develops in 3% of amiodarone-treated patients in North America. AIT is classified as type 1 or type 2. Type 1 AIT occurs in patients with underlying thyroid pathology such as autonomous nodular goiter or Graves’ disease. Type 2 AIT is a result of amiodarone causing a subacute thyroiditis with release of preformed thyroid hormones into the circulation. OBJECTIVES: To review the literature and present an overview of the differentiation between and management of type 1 and type 2 AIT. METHODS: PubMed, the Cumulative Index to Nursing and Allied Health Literature and Medscape searches of all available English language articles from 1983 to 2006 were performed. Search terms included ‘amiodarone-induced thyrotoxicosis’, ‘complications’, ‘management’, ‘treatment’ and ‘colour flow Dopper sonography’. RESULTS: There is evidence to suggest that to differentiate between type 1 and type 2 AIT, a careful history and physical examination should be performed to identify pre-existing thyroid disease. An iodine-131 uptake test and colour flow Doppler sonography should be performed. Patients with type 2 AIT should receive a trial of glucocorticoids, whereas those with type 1 should receive antithyroid therapy. For patients in whom the mechanism of the thyrotoxicosis is unclear, a combination of prednisone and antithyroid therapy may be considered. PMID:19584973

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro.

PubMed

Adamczewski, Zbigniew; Stasiołek, Mariusz; Karwowski, Bolesław; Dedecjus, Marek; Orszulak-Michalak, Daria; Merecz, Anna; Śliwka, Przemysław W; Puła, Bartosz; Lewiński, Andrzej

2015-06-29

Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis.

Elevated Serum Triiodothyronine and Intellectual and Motor Disability with Paroxysmal Dyskinesia Caused by a Monocarboxylate Transporter 8 Gene Mutation

ERIC Educational Resources Information Center

Fuchs, Oliver; Pfarr, Nicole; Pohlenz, Joachim; Schmidt, Heinrich

2009-01-01

"Monocarboxylate transporter 8" ("MCT8" or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan-Herndon-Dudley syndrome…

Thyrotoxicosis induced by excessive 3,5,3'-triiodothyronine in a dog.

PubMed

Morré, Wendy A; Panciera, David L; Daniel, Gregory B; Refsal, Kent R; Rick, Markus; Arrington, Kathy

2017-06-15

CASE DESCRIPTION A 7-year-old castrated male Havanese was evaluated at a veterinary teaching hospital because of a 12-week history of hyperactivity, aggression, and progressive weight loss despite a healthy appetite. CLINICAL FINDINGS Tachycardia was the only remarkable finding during physical examination. Serum 3,5,3'-triiodothyronine (T3) and free T3 concentrations were markedly increased, and thyroxine (T4), free T4, and thyroid-stimulating hormone concentrations were at or decreased from the respective reference ranges. Thyroid scintigraphy revealed suppressed uptake of sodium pertechnetate Tc 99m by the thyroid gland but no ectopic thyroid tissue, which was indicative of thyrotoxicosis induced by an exogenous source of T3. TREATMENT AND OUTCOME The dog was hospitalized for 24 hours, and its diet was changed, after which the clinical signs rapidly resolved and serum T3 and free T3 concentrations returned to within the respective reference ranges. This raised suspicion of an exogenous source of T3 in the dog's home environment. Analysis of the commercial beef-based canned food the dog was being fed revealed a high concentration of T3 (1.39 μg/g) and an iodine (82.44 μg/g) concentration that exceeded industry recommendations. No other source of T3 was identified in the dog's environment. CLINICAL RELEVANCE To our knowledge, this is the first report of clinical thyrotoxicosis in a dog induced by exogenous T3, although the source of exogenous T3 was not identified. This case highlights the importance of measuring serum T3 and thyroid-stimulating hormone concentrations in addition to T4 and free T4 concentrations when there is incongruity between clinical findings and thyroid function test results.

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

PubMed

Christenson, W R; Becker, B D; Wahle, B S; Moore, K D; Dass, P D; Lake, S G; Van Goethem, D L; Stuart, B P; Sangha, G K; Thyssen, J H

1996-02-01

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Potential of (18)F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies.

PubMed

Vijayant, Vishu; Sarma, Manjit; Aurangabadkar, Hrushikesh; Bichile, Lata; Basu, Sandip

2012-12-28

To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and non-symmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. (18)F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.

Thyroid Nodules in Pediatrics: Which Ones Can Be Left Alone, Which Ones Must be Investigated, When and How

PubMed Central

Corrias, Andrea; Mussa, Alessandro

2013-01-01

Thyroid nodules are less frequent in childhood than in adulthood, but are more often malignant. Recent estimates suggest that up to 25% of thyroid nodules in children are malignant, therefore, a more aggressive approach is recommended. In this review, we suggest an approach based on a first-step clinical, laboratory, and sonographic evaluation. A history of irradiation of the neck, cranium or upper thorax, previous thyroid diseases or thyroid neoplasms in the family should alert clinicians as being associated with a greater likelihood of malignant nodules. Signs or symptoms of hyperthyroidism and dysmorphic features should be carefully considered during the physical examination. Palpable firm lymph nodes, found in some 70% of cases, are the most significant clinical finding in children with malignant nodules. Although the routine determination of calcitonin levels is not uniformly practiced, it can help recognize sporadic or familial medullary thyroid neoplasms. Blood thyroid stimulating hormone, free thyroxine, and free triiodothyronine determinations (the latter in case of symptoms of hyperthyroidism) are aimed at identifying the few hyperthyroid patients, for whom the next step should be scintiscan. Hyperthyroid patients usually disclose an increased uptake, and a diagnosis of toxic adenoma is commonly made. Cases with normal thyroid function or hypothyroidism (which is usually subclinical) should be evaluated by fine-needle aspiration biopsy (FNAB). In eu/hypo-thyroid patients, scintiscan provides poor diagnostic information and should not be routinely employed. Thyroid ultrasonography is used to select cases for FNAB. Although ultrasound cannot reliably discriminate between benign and malignant lesions, it does provide an index of suspicion. Sonographic features that increase the likelihood of malignancy are microcalcifications, lymph node alterations, nodule growth under levothyroxine treatment, and increased intranodular vascularization demonstrated by color Doppler. There is growing evidence that elastography may provide further information on nodule characteristics. FNAB is indicated in all cases with a likelihood of malignancy. FNAB has a diagnostic accuracy of approximately 90% and is used in selection of patients which require surgery. Recently, histological markers and elastography have been introduced to increase the specificity of FNAB and ultrasound, respectively. The pitfall in FNAB cytology is the follicular cytology, in which it is not possible to distinguish between adenoma and carcinoma and therefore thyroidectomy is advised. Conflict of interest:None declared. PMID:23165002

Predictive factors of outcomes in personalized radioactive iodine ((131)I) treatment for Graves' disease.

PubMed

Liu, Min; Jing, Danqing; Hu, Jingsheng; Yin, Shinan

2014-10-01

Graves' disease (GD) is the most common cause of hyperthyroidism in iodine-sufficient areas. Radioactive iodine I treatment (RIT), as the 1st therapeutic option, is widely accepted by doctors and patients. The aim of this study was to investigate factors influencing the success rate of calculated RIT in GD. Thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was verified retrospectively at least 1 year after RIT and was compared with presenting clinical characteristics and pre-RIT parameters in 167 patients with GD treated with I-iodide in the authors' institute. After RIT, 83 patients (49.7%) became euthyroid, 64 patients (38.3%) became hypothyroid and 20 (12.0%) remained hyperthyroid. Multiple logistic regression analyses demonstrated that there was no statistically significant association between RIT outcomes and sex, age, history of GD, previous antithyroid drug treatment, thyroid hormone levels, thyroid gland mass or radioactive iodine I dosage. The only variables associated with the success rate were the course of disease over 6 months (odds ratio, 3.70; confidence interval, 1.75-7.17; P = 0.014) and 2-hour radioactive iodine uptake (RAIU) >58.5% (odds ratio, 4.08; confidence interval, 2.03-7.83; P = 0.005). Our study has shown that a calculated approach for the treatment of GD was effective, but high failure rates were observed in patients presenting higher 2-hour RAIU, particularly those with 2-hour RAIU of more than 58.5%.

Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.

PubMed

Wirth, Eva K; Roth, Stephan; Blechschmidt, Cristiane; Hölter, Sabine M; Becker, Lore; Racz, Ildiko; Zimmer, Andreas; Klopstock, Thomas; Gailus-Durner, Valerie; Fuchs, Helmut; Wurst, Wolfgang; Naumann, Thomas; Bräuer, Anja; de Angelis, Martin Hrabé; Köhrle, Josef; Grüters, Annette; Schweizer, Ulrich

2009-07-29

Thyroid hormone transport into cells requires plasma membrane transport proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3',3,5-triiodothyronine (T(3)) plasma levels. Mice deficient in Mct8 replicate the thyroid hormone abnormalities observed in the human condition. However, no neurological deficits have been described in mice lacking Mct8. Therefore, we subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Several behavioral abnormalities were found in the mutants. Interestingly, some of these behavioral changes are compatible with hypothyroidism, whereas others rather indicate hyperthyroidism. We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T(3) transporters become hyperthyroid, if they are exposed directly to the high plasma T(3). The majority of T(3) uptake in primary cortical neurons is mediated by Mct8, but pharmacological inhibition suggested functional expression of additional T(3) transporter classes. mRNAs encoding six T(3) transporters, including L-type amino acid transporters (LATs), were coexpressed with Mct8 in isolated neurons. We then demonstrated Lat2 expression in cultured neurons and throughout murine brain development. In contrast, LAT2 is expressed in microglia in the developing human brain during gestation, but not in neurons. We suggest that lack of functional complementation by alternative thyroid hormone transporters in developing human neurons precipitates the devastating neurodevelopmental phenotype in MCT8-deficient patients, whereas Mct8-deficient mouse neurons are functionally complemented by other transporters, for possibly Lat2.

Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma.

PubMed

Choi, Eun Kyoung; Chong, Ari; Ha, Jung-Min; Jung, Chan Kwon; O, Joo Hyun; Kim, Sung Hoon

2017-07-01

We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data. This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumour using quantitative and qualitative analyses of preoperative PET/CT data. Clinicopathological data included the primary tumour size, subtype, capsular invasion, extrathyroid extension, multifocality, BRAF V600E mutation status, lymph node metastasis and distant metastasis. The SUVmax of the primary tumour was significantly higher in patients with a primary tumour >1 cm, extrathyroid extension or the BRAF V600E mutation than in patients without these features (P<.001, .049 and <.001). Univariate analyses showed that primary tumour size, extrathyroid extension and BRAF V600E mutation status were associated with the SUVmax of the PTC. Multivariate analysis indicated that primary tumour size and the BRAF V600E mutation were associated with the SUVmax of the PTC. In a visual assessment, the primary tumour size was larger in FDG-avid than in non-FDG-avid PTCs (P<.001). There was no significant difference in the presence of multifocality, thyroid capsular invasion, extrathyroid extension, BRAF V600E mutation, lymph node metastasis or distant metastasis between FDG-avid and non-FDG-avid PTCs. Primary tumour size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC. © 2017 John Wiley & Sons Ltd.

Congenital hypothyroidism

PubMed Central

2010-01-01

Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis of infants detected by screening and started on treatment early is excellent, with IQs similar to sibling or classmate controls. Studies show that a lower neurocognitive outcome may occur in those infants started at a later age (> 30 days of age), on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism. PMID:20537182

Hyperthyroidism: diagnosis and treatment.

PubMed

Reid, Jeri R; Wheeler, Stephen F

2005-08-15

The proper treatment of hyperthyroidism depends on recognition of the signs and symptoms of the disease and determination of the etiology. The most common cause of hyperthyroidism is Graves' disease. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications. The diagnostic workup begins with a thyroid-stimulating hormone level test. When test results are uncertain, measuring radionuclide uptake helps distinguish among possible causes. When thyroiditis is the cause, symptomatic treatment usually is sufficient because the associated hyperthyroidism is transient. Graves' disease, toxic multinodular goiter, and toxic adenoma can be treated with radioactive iodine, antithyroid drugs, or surgery, but in the United States, radioactive iodine is the treatment of choice in patients without contraindications. Thyroidectomy is an option when other treatments fail or are contraindicated, or when a goiter is causing compressive symptoms. Some new therapies are under investigation. Special treatment consideration must be given to patients who are pregnant or breastfeeding, as well as those with Graves' ophthalmopathy or amiodarone-induced hyperthyroidism. Patients' desires must be considered when deciding on appropriate therapy, and dose monitoring is essential.

[Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case].

PubMed

Hurtado, Claudia; Báez, María Soledad; Bate, Anabel; Opazo, Claudio; Troncoso, Mauricio

2017-05-01

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways.

PubMed

Zhao, L M; Pang, A X

2017-01-16

Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways.

Studies of peripheral thyroxine distribution in thyrotoxicosis and hypothyroidism.

PubMed

Nicoloff, J T; Dowling, J T

1968-09-01

Compartmental analysis of the peripheral distribution of labeled thyroxine was applied to various groups of subjects with thyrotoxicosis and hypothyroidism. It was observed that the hepatic incorporation of thyroxine was augmented in subjects with Graves' disease when compared to non-Graves' disease control groups at all levels of thyroid function. Decreased values of hepatic incorporation occurred in primary hypothyroid subjects. These lowered values were not acutely corrected by elevation of the serum thyroxine level, but were observed to be rectified after several months' therapy with exogenous thyroid hormone. These alterations of the hepatic thyroxine-(131)I incorporation were independently verified by direct quantitative liver scintiscan determinations. Employing a dual thyroxine tracer system, we were able to demonstrate that during the early phases of equilibration of a tracer dose of thyroxine, alterations in the rate of deiodination were observed to be present in the various thyroid disease states. Increased deiodination rates were found in subjects with Graves' disease and the reverse was noted in patients with primary hypothyroidism. Kinetic analysis of thyroxine compartmental distribution during this early phase of equilibration of a labeled thyroxine tracer indicated that the primary tissue uptake occurred in the liver. These findings supported the contention that the amount of labeled thyroxine incorporated in the liver may be directly related to the deiodination rate of thyroxine by that organ. The pathogenetic basis of these alterations is presently unknown.

Effect of the cardiac inotropic drug, OPC 8212, on pituitary-thyroid function in the rat.

PubMed

Lueprasitsakul, W; Fang, S L; Alex, S; Braverman, L E

1991-06-01

3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 piperaznyl]-2(1H)-quinolinone (OPC 8212) is a new synthetic quinolinone with potent cardiac inotropic action in man. Long term oral administration of OPC induces goiter and thyroid tumor formation in rats, associated with decreases in serum T4 and increases in serum TSH concentrations. Studies were carried out to explore the mechanisms responsible for these drug induced abnormalities. OPC 8212, administered for 1 week at doses of 500 and 2000 mg/kg.day mixed with the diet, resulted in an increase in thyroid weight, a decrease in circulating T4 and free T4 concentrations and an increase in serum TSH concentrations. OPC decreased the 5'-deiodinase (5'-D) activity in liver homogenates and increased the 5'-D activity in pituitary homogenates, consistent with hypothyroidism. OPC 8212 did not affect thyroid iodine metabolism and hormone synthesis or the binding of T4 to serum binding proteins. The hepatic uptake of 125 I-T4 4 h after T4 administration was significantly increased in OPC 8212 treated rats. The biliary excretion of administered 125 I-T4 was increased in OPC 8212-treated rats and most of the increase was due to an increase in the excretion of T4-glucuronide. Hepatic T4-glucuronyltransferase activity measured in vitro in OPC 8212 treated rats was increased as compared to that of controls. It is concluded that the effect of OPC 8212 on lowering serum T4 with a compensatory rise in TSH leading to goiter formation is due to a drug-induced increase in hepatic T4 disposal. The induction of T4-glucuronyl-transferase appears to play an important role in the increased biliary excretion of T4 in OPC 8212-treated rats.

Novel biomarkers of perchlorate exposure in zebrafish

USGS Publications Warehouse

Mukhi, S.; Carr, J.A.; Anderson, T.A.; Patino, R.

2005-01-01

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T 4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates. ?? 2005 SETAC.

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

PubMed

Farahati, J; Bier, D; Scheubeck, M; Lassmann, M; Schelper, L F; Grelle, I; Hanscheid, H; Biko, J; Graefe, K H; Reiners, C

1997-03-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

PubMed

Kyrilli, Aglaia; Tang, Bich-Ngoc-Thanh; Huyge, Valérie; Blocklet, Didier; Goldman, Serge; Corvilain, Bernard; Moreno-Reyes, Rodrigo

2015-06-01

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Lithium as an adjunct to radioactive iodine for the treatment of hyperthyroidism: a systematic review and meta-analysis.

PubMed

Kessler, Lynn; Palla, Jyothsna; Baru, Joshua S; Onyenwenyi, Chioma; George, Amrutha M; Lucas, Brian P

2014-07-01

Radioactive iodine (RAI) is commonly used in the treatment of hyperthyroidism but is not uniformly successful. Lithium increases thyroidal iodine retention without reducing iodide uptake, increasing the radiation dose to the thyroid when administered with RAI. Although these actions suggest that adjuvant lithium may increase the efficacy of RAI, its role as an adjunct to RAI remains contentious. To evaluate the safety and efficacy of adding lithium to RAI to treat hyperthyroidism. Relevant studies were identified by a search of Medline and the Cochrane Central Register of Controlled Trials. To be included, a study had to be a controlled trial comparing the effect of RAI alone to RAI with lithium in the treatment of hyperthyroidism. Relevant data were extracted and meta-analyses were performed. Of the 75 identified studies, 6 met the inclusion criteria; 4 of these studies were interventional and 2 were observational trials. Meta-analysis of the observational trials (N = 851), both of which were retrospective cohort studies, showed significant improvement in the primary outcome (i.e., cure rate) with adjunctive lithium (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.24 to 2.96). The combined interventional trials (N = 485) also showed an improvement in cure rate, but the difference did not reach statistical significance (OR, 1.28; 95% CI, 0.85 to 1.91). Adjunctive lithium reduced time to cure and blunted thyroid hormone excursions after RAI. Lithium-related side effects were infrequent and usually mild. The observational trials demonstrated significant improvement in the cure rate of hyperthyroidism when lithium is added to RAI. The improvements shown in the interventional trials did not reach statistical significance due to the effect of a single, large negative trial.

Congenital hypothyroidism in infant following maternal I 131 therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, William D.; Voorhess, Mary L.; Gardner, Lytt I.

1963-01-01

The case history is cited of an infant with congenital hypothyroidism whose mother had received 14.5 mC I 131 as therapy for Graves' disease during the end of the first trimester of pregnancy. It was estimated that the fetal thyroid received around 250000 rad, contrasted with the usual estimated 10000 to 20000 rad for the thyroid of adults treated for hyperthyroidism. The infant when seen at the age of 18 months showed marked retardation in growth and in physical and mental development. The danger of I 131 therapy to women of child-bearing age is emphasized. An extensive discussion is givenmore » on the hazards of radioactive isotopes in the environment to children, the description of the fallout pattern of Sr 90 in the U. S. and the difficulties in accurately estimating its danger to children, several possible approaches to the reduction of dietary Sr 90, I 131 contamination of the environment, and the use of nonradioactive iodide to interfere with the thyroidal uptake of I 131. The case record data of 4 other infants with congenital hypothyroidism whose mothers underwent I 131 therapy during pregnancy are also cited. Recommendations are provided for avoiding radiation injury to the fetal thyroid as well as for generally lowering the fetal, infant, and maternal incorporation of radionuclides of fallout origin.« less

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro

PubMed Central

Adamczewski, Zbigniew; Stasiołek, Mariusz; Karwowski, Bolesław; Dedecjus, Marek; Orszulak-Michalak, Daria; Merecz, Anna; Śliwka, Przemysław W.; Puła, Bartosz; Lewiński, Andrzej

2015-01-01

Background: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). Materials and Methods: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. Results: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. Conclusions: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the “thyroid stunning” reduces the NIS protein synthesis. PMID:26132566

Iodine distribution in the environment as a limiting factor for roe deer antler development.

PubMed

Lehoczki, Róbert; Erdélyi, Károly; Sonkoly, Krisztina; Szemethy, László; Csányi, Sándor

2011-02-01

The iodine-containing hormones produced by the thyroid gland play a role in the complex neuro-hormonal regulation of antler development. The proper function of the thyroid depends on the adequate iodine supply of the organism, which is directly related to the iodine content of food and drinking water. The purpose of this study was to explore the connection between the iodine content of the water base, which has a strong correlation with the iodine concentration of environmental components available to animals, and the antler weight of roe deer (Capreolus capreolus) shot in Hungarian hunting areas. Using a general linear model, controlling for the collective effects of other environmental factors (deer population density, harvest rate, land use, and soil fertility information), the iodine content of the water base explained 51.4% of the total variance of antler weights. The results suggest that antler weights increase with increasing iodine concentration regardless of other factors; thus, the environmental iodine distribution can be a limiting factor suppressing roe deer performance assessed here as antler weight. Further experimental studies of controlled iodine uptake are needed to define the exact physiological iodine requirements of roe deer bucks.

Occurrence of perchlorate and thiocyanate in human serum from e-waste recycling and reference sites in Vietnam: association with thyroid hormone and iodide levels.

PubMed

Eguchi, Akifumi; Kunisue, Tatsuya; Wu, Qian; Trang, Pham Thi Kim; Viet, Pham Hung; Kannan, Kurunthachalam; Tanabe, Shinsuke

2014-07-01

Perchlorate (ClO4 (-)) and thiocyanate (SCN(-)) interfere with iodide (I(-)) uptake by the sodium/iodide symporter, and thereby these anions may affect the production of thyroid hormones (THs) in the thyroid gland. Although human exposure to perchlorate and thiocyanate has been studied in the United States and Europe, few investigations have been performed in Asian countries. In this study, we determined concentrations of perchlorate, thiocyanate, and iodide in 131 serum samples collected from 2 locations in Northern Vietnam, Bui Dau (BD; electrical and electronic waste [e-waste] recycling site) and Doung Quang (DQ; rural site) and examined the association between serum levels of these anions with levels of THs. The median concentrations of perchlorate, thiocyanate, and iodide detected in the serum of Vietnamese subjects were 0.104, 2020, and 3.11 ng mL(-1), respectively. Perchlorate levels were significantly greater in serum of the BD population (median 0.116 ng mL(-1)) than those in the DQ population (median 0.086 ng mL(-1)), which indicated greater exposure from e-waste recycling operations by the former. Serum concentrations of thiocyanate were not significantly different between the BD and DQ populations, but increased levels of this anion were observed among smokers. Iodide was a significant positive predictor of serum levels of FT3 and TT3 and a significant negative predictor of thyroid-stimulating hormone in males. When the association between serum levels of perchlorate or thiocyanate and THs was assessed using a stepwise multiple linear regression model, no significant correlations were found. In addition to greater concentrations of perchlorate detected in the e-waste recycling population, however, given that lower concentrations of iodide were observed in the serum of Vietnamese females, detailed risk assessments on TH homeostasis for females inhabiting e-waste recycling sites, especially for pregnant women and their neonates, are required.

Free and total thyroid hormones in humans at extreme altitude

NASA Astrophysics Data System (ADS)

Basu, Minakshi; Pal, K.; Malhotra, A. S.; Prasad, R.; Sawhney, R. C.

1995-03-01

Alterations in circulatory levels of total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), thyrotropin (TSH) and T3 uptake (T3U) were studied in male and female sea-level residents (SLR) at sea level, in Armed forces personnel staying at high altitude (3750 m) for prolonged duration (acclimatized lowlanders, ALL) and in high-altitude natives (HAN). Identical studies were also performed on male ALL who trekked to an extreme altitude of 5080 m and stayed at an altitude of more than 6300 m for about 6 months. The total as well as free thyroid hormones were found to be significantly higher in ALL and HAN as compared to SLR values. Both male as well as female HAN had higher levels of thyroid hormones. The rise in hormone levels in different ALL ethnic groups drawn from amongst the southern and northern parts of the country was more or less identical. In both HAN and ALL a decline in FT3 and FT4 occurred when these subjects trekked at subzero temperatures to extreme altitude of 5080 m but the levels were found to be higher in ALL who stayed at 6300 m for a prolonged duration. Plasma TSH did not show any appreciable change at lower altitudes but was found to be decreased at extreme altitude. The increase in thyroid hormones at high altitude was not due to an increase in hormone binding proteins, since T3U was found to be higher at high altitudes. A decline in TSH and hormone binding proteins and an increase in the free moiety of the hormones is indicative of a subtle degree of tissue hyperthyroidism which may be playing an important role in combating the extreme cold and hypoxic environment of high altitudes.

[Thyroid echogeneity as a useful tool for the differential diagnosis of hyperthyroidism in the course of Graves disease and Hashimoto thyroiditis].

PubMed

Niedziela, M; Warzywoda, M; Korman, E

2000-01-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) constitute a spectrum of autoimmune thyroid diseases (AITD). They share an autoimmune pathogenesis, with a cellular and a humoral response to the thyroid gland. As a consequence, dysfunction of the gland itself may develop, characterized by hyperfunction in the case of GD and hypofunction in the case of HT, however at the onset of HT the hyperthyroidism might be observed as a result of a rapid destruction of thyrocytes. An abnormal thyroid echographic pattern characterized by a diffuse low echogeneity has been described in both AITD. This hypoechogeneity is due to three components: increase of intrathyroidal flow, functional changes in thyroid follicles with increased cellularity and decrease of the colloid content, resulting in the reduction of the cell/colloid interface, variable degree of lymphocytic infiltration. The first two components may be reversible during medical treatment and seem to be characteristic for GD, whereas lymphocytic infiltration may rather represent mostly HT. Here we present a 17-year-old girl with typical clinical signs of hyperthyroidism [firm goiter (II degrees), tachycardia, palpitations, nervousness, excessive sweating and tremor]. Laboratory tests were the following: fT3 - 6.59 pg/ml(increasing), fT4 - 1.99 ng/dl(increasing), TSH - 0.02 micro IU/ml(decreasing); anti-Tg-Ab - 840 IU/ml(increasing), anti-TPO-Ab - 190 IU/ml(increasing) (4 months later antithyroid antibodies were 2200 and 70, respectively). Ultrasound examination showed hypoechogeneity of the whole gland and enhanced vascular flow based on power Doppler analysis. Thyroid scan visualized the generally increased uptake of technetium. The girl was put on beta-blocker (propranolol) and later an antithyroid drug (thiamazole) was added. A course of disease was unstable, therefore the fine-needle aspiration biopsy was performed and showed the presence of single groups of normal thyrocytes and scanty colloid with no features of HT. Power Doppler analysis showed still enhanced blood flow within a gland inspite of euthyroid state. After a very unsteady period of the disease, the euthyroid state is maintained although the medical treatment was given up. The full recovery of normal blood flow and normal echogeneity of the thyroid was documented. The latter supports the diagnosis of GD. Follow-up of the thyroid echogeneity is of great diagnostic and prognostic value if the assay of TSHR-Ab is not available. On the other side, it has to be remembered that TSHR-Ab do not have to be positive in patients with GD and can be positive in patients with HT.

A Pilot Comparison of 18F-fluorocholine PET/CT, Ultrasonography and 123I/99mTc-sestaMIBI Dual-Phase Dual-Isotope Scintigraphy in the Preoperative Localization of Hyperfunctioning Parathyroid Glands in Primary or Secondary Hyperparathyroidism

PubMed Central

Michaud, Laure; Balogova, Sona; Burgess, Alice; Ohnona, Jessica; Huchet, Virginie; Kerrou, Khaldoun; Lefèvre, Marine; Tassart, Marc; Montravers, Françoise; Périé, Sophie; Talbot, Jean-Noël

2015-01-01

Abstract We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted). The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases. In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia. This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope 123I/99mTc-scintigraphy. Further studies should evaluate whether FCH could replace 99mTc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions. PMID:26469908

Mechanistic aspects of ingested chlorine dioxide on thyroid function: impact of oxidants on iodide metabolism.

PubMed Central

Bercz, J P; Jones, L L; Harrington, R M; Bawa, R; Condie, L

1986-01-01

Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO2) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO2 ingestion, it seems that ClO2 does not cause iodide deficiency of sufficient magnitude to account for the decrease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrients, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen. Images FIGURE 1. a FIGURE 1. b FIGURE 1. c PMID:3816729

Analysis of ¹³¹I therapy and correlation factors of Graves' disease patients: a 4-year retrospective study.

PubMed

Zheng, Wei; Jian, Tan; Guizhi, Zhang; Zhaowei, Meng; Renfei, Wang

2012-01-01

To analyze the correlation therapeutic effects of first sufficiency ¹³¹I therapy in Graves' disease patients and improve its one-time curative ratio. Seven hundred and sixty-six patients (age range 12-77 years, mean 40.46 ± 13.12 years), including 237 men (range 12-77 years, 40.98 ± 12.64 years) and 529 women (range 14-75 years, 40.22 ± 13.34 years), who received the first I treatment were studied. The relevant examinations were performed before ¹³¹I therapy: the maximal radioactive iodine uptake of thyroid (RAIUmax), the effective half-life (EHL), the ultrasound of thyroid to calculate its weight, thyroid imaging with single-photon emission computed tomography and serum-free triiodothyronine (FT₃), free thyroxine (FT₄), sensitive thyroid-stimulating hormone (sTSH), anti-thyrotrophin receptor antibody (TRAb), thyroid-stimulating immunoglobulin, thyroglobulin antibody (TgAb), and anti-thyroid microsome antibody (TMAb). After the ¹³¹I dosage was determined, all the patients took ¹³¹I once orally. The ¹³¹I dosage range was 74-592 MBq (221.63 ± 100.64 MBq). A clinical and laboratory assessment was performed at 1, 3, 6, and 12 months after ¹³¹I therapy. Patients were divided into the clinically recovered group (symptoms and signs disappeared, free thyroid hormone levels were within or below the normal range, and sTSH was within or above the normal range) and the clinically unhealed group (symptoms and signs disappeared partially, free thyroid hormone levels were still above the normal range or within the normal range for a time and then increased again, and sTSH was constantly below the normal range). Data were analyzed by the unpaired t-test, the independent samples t-test, the χ² test, logistic regression, and Pearson bivariate correlation. The one-time curative ratio of ¹³¹I therapy was 78.7% (including euthyroidism and hypothyroidism). Multiplicity in healing patients fit the logistic regression equation. The accuracy of discrimination of the equation was 79.5%. The influential factors of ¹³¹I therapy were age, RAIUmax, EHL, TRAb, and TgAb. RAIUmax and EHL were the protecting factors. Age, TRAb, and TgAb were the risk factors. TRAb influenced the one-time curative ratio between patients with negative and positive TRAb, which was higher in men (2.836 times) than in women (1.438 times). ¹³¹I therapy is an effective intervention for Graves' disease. The higher the RAIUmax and (or) the longer the EHL, the higher the possibility of a one-time cure. Elder patients or patients with a positive TRAb and (or) TgAb have a lower possibility of a one-time cure. Women with a positive TRAb should be administered an increased ¹³¹I dose to improve the curative effect.

Implementation of the Bethesda System for Reporting Thyroid Cytopathology: observations from the 2011 thyroid supplemental questionnaire of the College of American Pathologists.

PubMed

Auger, Manon; Nayar, Ritu; Khalbuss, Walid E; Barkan, Güliz A; Benedict, Cynthia C; Tambouret, Rosemary; Schwartz, Mary R; Howell, Lydia P; Souers, Rhona J; Hartley, David A; Thomas, Nicole; Moriarty, Ann T

2013-11-01

Although information about the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely disseminated since its inception in 2007, the extent of its implementation and impact on daily practice has not been formally evaluated. To assess the extent of uptake of TBSRTC across pathology laboratories and to evaluate its impact on daily practice by collating participant responses to the 2011 supplemental thyroid questionnaire of the College of American Pathologists. A questionnaire was designed to gather information about various aspects of TBSRTC and mailed in June 2011 to 2063 laboratories participating in the College of American Pathologists cytopathology interlaboratory comparison program. The participating laboratories' answers were collated and summarized. Seven hundred and seventy-seven laboratories (37.6%) returned the survey. Although 60.9% (n = 451) and 17.1% (n = 127) of laboratories reported using TBSRTC or planning to use it in the near future, respectively, 22% (n = 163) had no plans to implement TBSRTC. Of the latter, 32% (n = 70) stated that they were unaware of this classification system. The majority (78.3%, n = 343) of the laboratories used TBSRTC as published in the Thyroid Bethesda System atlas, whereas 21.7% (n = 95) used it with minor modifications. Most reported that the use of TBSRTC had caused either no change (n = 67, 15.2%) or only minor changes (n = 353, 80.2%) in the terminology and diagnostic criteria previously used in their laboratories. According to the collected data, TBSRTC is generally well implemented in pathology laboratories. However, because approximately a third of those not using this terminology are not aware of it, additional educational efforts regarding TBSRTC are warranted.

Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues.

PubMed

Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

2014-06-01

In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. © 2014 The authors.

Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism.

PubMed

Pavelka, S

2014-01-01

We newly elaborated and adapted several radiometric enzyme assays for the determination of activities of the key enzymes engaged in the biosynthesis (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland and in peripheral tissues, especially in white adipose tissue (WAT). We also elaborated novel, reliable radiometric methods for extremely sensitive determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal fractions of different rat and human tissues, as well as in homogenates of cultured mammalian cells. The use of optimized TLC separation of radioactive products from the unconsumed substrates and film-less autoradiography of radiochromatograms, taking advantage of storage phosphor screens, enabled us to determine IDs enzyme activities as low as 10(-18) katals. In studies of the interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used representative of a new group of non-tricyclic antidepressant drugs--selective serotonin re-uptake inhibitors. We used the elaborated assays for quantification the effects of Fluox and for the assessment of the degree of potential induction of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination with T(3). Furthermore, we studied possible changes in IDs activities in murine adipose tissue under the conditions that promoted either tissue hypertrophy (obesogenic treatment) or involution (caloric restriction), and in response to leptin, using our newly developed radiometric enzyme assays for IDs. Our results suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue. Significant positive correlation between specific enzyme activity of D1 in WAT and plasma leptin levels was found. The newly developed and adapted radiometric enzyme assays proved to be very useful tools for studies of factors modulating THs metabolism, not only in model animals but also in clinical studies of human obesity.

Ultrasound, elastography, and fluorodeoxyglucose positron emission tomography/computed tomography imaging in Riedel's thyroiditis: report of two cases.

PubMed

Slman, Rouba; Monpeyssen, Hervé; Desarnaud, Serge; Haroche, Julien; Fediaevsky, Laurence Du Pasquier; Fabrice, Menegaux; Seret-Begue, Dominique; Amoura, Zahir; Aurengo, André; Leenhardt, Laurence

2011-07-01

Riedel's thyroiditis (RT) is a rare disease characterized by a chronic inflammatory lesion of the thyroid gland with invasion by a dense fibrosis. Publications of the imaging features of RT are scarce. To our knowledge, ultrasound elastography (USE) findings have not been previously reported. Therefore, we describe two patients with RT who were imaged with ultrasonography (US), USE, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Two women were referred for a large, hard goiter with compressive symptoms (dyspnea and dysphagia); in one patient, the goiter was associated with retroperitoneal fibrosis. In both cases, RT was confirmed by surgical biopsy with pathological examination. Thyroid US imaging was performed with a US scan and a 10-13 MHz linear transducer. The hardness of the tissues was analyzed using transient USE (ShearWave, Aixplorer-SuperSonic Imagine). PET/CT scanning was performed with a Philips Gemini GXL camera (GE Medical Systems). In the first patient, US examination revealed a compressive multinodular goiter with large solid hypoechoic and poorly vascularized areas adjacent to the nodules. The predominant right nodule was hypoechoic with irregular margins. The second patient had a hypoechoic goiter with large bilateral hypoechoic areas. In both cases, an unusual feature was observed: the presence of tissue surrounding the primitive carotid artery, associated with thrombi of the internal jugular vein. Further, USE showed heterogeneity in the stiffness values of the thyroid parenchyma varying between 21 kPa and 281 kPa. FDG-PET/CT imaging showed uptake foci in the thyroid gland. In both cases, US showed a decrease in the thyroid gland volume and the disappearance of encasement of the neck vasculature in response to corticosteroid treatment. In contrast, the FDG-PET/CT features remained unchanged. US features, such as vascular encasement and improvement under corticosteroid treatment, seem to be specific to this rare disease. For the first time, USE documents the hardness of RT tissues. Apart from the FDG-PET/CT findings that merit further investigation, US and USE prove useful tools in the assessment of such a rare disease.

Antiphospholipid Antibody Syndrome Associated with Graves’ Disease Presenting As Inferior Vena Cava Thrombosis with Bilateral Lower Limb DVT

PubMed Central

Jain, Ankur

2014-01-01

We report a case of a 60-year-old lady who presented with bilateral lower limb swelling and a thyroid swelling with clinical features consistent with thyrotoxicosis. Investigations revealed the presence of a thrombus in bilateral external, internal iliac veins, and inferior vena cava extending up to its infrahepatic part. Hormone profile and radioiodine uptake scan confirmed the diagnosis of Graves’ disease. Further workup revealed the presence of antiphospholipid antibodies (confirmed after a repeat test at 12 weeks). The patient was treated with antithyroid drugs and anticoagulants. The patient improved with normalization of thyroid function and partial recanalization of the infrahepatic part of inferior vena cava. Hyperthyroidism has been implicated as a potential hypercoagulable state; however, the association of Graves’ disease with antiphospholipid antibody syndrome is limited to isolated case reports. This case highlights a new mechanism underlying hypercoagulability associated with Graves’ disease. PMID:24812529

Use of Iodine-131 to Tellurium-132 Ratios for Assessing the Relationships between Human Inhaled Radioactivity and Environmental Monitoring after the Accident in Fukushima.

PubMed

Uchiyama, Koji; Miyashita, Masami; Tanishima, Yoshinobu; Maeda, Shigenobu; Sato, Hitoshi; Yoshikawa, Jun; Watanabe, Shuji; Shibata, Masamichi; Ohhira, Shuji; Kobashi, Gen

2018-03-09

Significant differences in findings were seen between the intake amounts of iodine-131 that were derived from direct measurements and the estimated intake from environmental monitoring data at the Fukushima accident. To clarify these discrepancies, we have investigated the iodine-131 and tellurium-132 body burdens of five human subjects, who after being exposed to a radioactive plume, underwent 21.5 h whole body counter measurements at Fukui Prefectural Hospital, so clear intake scenario and thyroid counter measurement data were available. To determine the iodine-131 and tellurium-132 body burdens, we introduced a new method of whole body counter calibration composed of a self-consistent approach with the time-dependent correction efficiency factors concept. The ratios of iodine-131 to tellurium-132, ranging from 0.96 ± 0.05 to 2.29 ± 0.38, were consistent with results of the environmental measurements. The 24 h iodine uptake values ranging from 12.1-16.0% were within euthyroid range in Japanese people. These results suggest, even if the relatively low thyroid iodine uptake in the Japanese population was taken into consideration, that there is no doubt about the consistency between direct measurements and environmental monitoring data. Adequate intake scenario is suggested to be principally important to estimate the inhaled radioactivity in areas in or around nuclear accidents.

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeGrado, Timothy R.; Kemp, Bradley J.; Pandey, Mukesh K.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B ( 11C-PiB) andmore » 18F-fluorodeoxyglucose ( 18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.« less

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases

PubMed Central

Nair, Rahul; Gambhir, Anushree; Kaur, Supreet; Pandey, Aditi; Shetty, Abhinav; Naragude, Piyusha

2018-01-01

Introduction Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. Aim Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). Materials and Methods The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. Results The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21–40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. Conclusion The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the “Gold Standard” for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical parameters are the key for diagnosis of other forms of thyroiditis. PMID:29686830

[Spectrometric assessment of thyroid depth within the radioiodine test].

PubMed

Rink, T; Bormuth, F-J; Schroth, H-J; Braun, S; Zimny, M

2005-01-01

Aim of this study is the validation of a simple method for evaluating the depth of the target volume within the radioiodine test by analyzing the emitted iodine-131 energy spectrum. In a total of 250 patients (102 with a solitary autonomous nodule, 66 with multifocal autonomy, 29 with disseminated autonomy, 46 with Graves' disease, 6 for reducing goiter volume and 1 with only partly resectable papillary thyroid carcinoma), simultaneous uptake measurements in the Compton scatter (210 +/- 110 keV) and photopeak (364-45/+55 keV) windows were performed over one minute 24 hours after application of the 3 MBq test dose, with subsequent calculation of the respective count ratios. Measurements with a water-filled plastic neck phantom were carried out to perceive the relationship between these quotients and the average source depth and to get a calibration curve for calculating the depth of the target volume in the 250 patients for comparison with the sonographic reference data. Another calibration curve was obtained by evaluating the results of 125 randomly selected patient measurements to calculate the source depth in the other half of the group. The phantom measurements revealed a highly significant correlation (r = 0,99) between the count ratios and the source depth. Using these calibration data, a good relationship (r = 0,81, average deviation 6 mm corresponding to 22%) between the spectrometric and the sonographic depths was obtained. When using the calibration curve resulting from the 125 patient measurements, the overage deviation in the other half of the group was only 3 mm (12%). There was no difference between the disease groups. The described method allows on easy to use depth correction of the uptake measurements providing good results.

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

PubMed

Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

2004-04-01

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

PubMed

Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

2012-01-01

Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

Hyperthyroid dementia: clinicoradiological findings and response to treatment.

PubMed

Fukui, T; Hasegawa, Y; Takenaka, H

2001-02-15

Dementia associated with hyperthyroidism is less well documented than is hypothyroid dementia. Therapeutic response of hyperthyroid dementia and associated cerebral circulatory and/or metabolic abnormalities has not been elucidated. We described a patient with hyperthyroid dementia and clinicoradiological response to treatment. Single photon emission computed tomographic (SPECT) study was repeated and analyzed semiquantitatively. A 67-year-old man experienced progressive impairments of attention, memory, constructive skills and behavior as well as hand tremor and weight loss of two-year duration. Laboratory findings were compatible with Graves' disease. The initial SPECT showed diffuse tracer uptake defect with an accentuation in the bilateral temporoparietal regions. Clinical and SPECT findings both suggested concurrent "possible" Alzheimer's disease. However, initial treatment with a beta-blocker improved behavior and attention-related cognitive functions as well as tracer uptake in the frontal lobes. Subsequent treatment with additional methimazole then improved memory and constructive abilities when a euthyroid state was established. Uptake defect in the temporoparietal regions also responded gradually to the medication. We suggest that the present patient represent hyperthyroid dementia, which responds favorably to treatment with regard to clinical symptoms and SPECT findings. We also suggest that thyroid function be measured in patients with "possible" Alzheimer's disease because treatable hyperthyroid dementia may not be identified.

Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis.

PubMed Central

Hard, G C

1998-01-01

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation. PMID:9681969

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of (99m)Tc versus (188)Re.

PubMed

Freudenberg, Robert; Wendisch, Maria; Runge, Roswitha; Wunderlich, Gerd; Kotzerke, Jörg

2012-12-01

Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of (188)Re-perrhenate and (99m)Tc-pertechnetate on cellular survival. Rat thyroid PC Cl3 cells in culture were incubated with (188)Re or (99m)Tc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified. Dose effect curves were established for (188)Re and (99m)Tc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and (188)Re reduced cell survival more efficiently than (99m)Tc. A(37), the activity that is necessary to yield 37% cell survival was 14 MBq/ml for (188)Re and 480 MBq/ml for (99m)Tc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A(37) was reduced by 30% for the beta-emitter and by 95% for (99m)Tc. The dose D(37) that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides. Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular (99m)Tc yielded a dose increase that was higher compared to (188)Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non-uniform lognormal radionuclide uptake.

First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease.

PubMed

DeGrado, Timothy R; Kemp, Bradley J; Pandey, Mukesh K; Jiang, Huailei; Gunderson, Tina M; Linscheid, Logan R; Woodwick, Allison R; McConnell, Daniel M; Fletcher, Joel G; Johnson, Geoffrey B; Petersen, Ronald C; Knopman, David S; Lowe, Val J

2016-01-01

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63 Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63 Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63 Zn clearances were compared with 11 C-Pittsburgh Compound B ( 11 C-PiB) and 18 F-fluorodeoxyglucose ( 18 F-FDG) imaging data. 63 Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63 Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11 C-PiB) and 18 F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63 Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD. © The Author(s) 2016.

First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease

DOE PAGES

DeGrado, Timothy R.; Kemp, Bradley J.; Pandey, Mukesh K.; ...

2016-01-01

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B ( 11C-PiB) andmore » 18F-fluorodeoxyglucose ( 18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.« less

Radioactive body burden measurements in (131)iodine therapy for differentiated thyroid cancer: effect of recombinant thyroid stimulating hormone in whole body (131)iodine clearance.

PubMed

Ravichandran, Ramamoorthy; Al Saadi, Amal; Al Balushi, Naima

2014-01-01

Protocols in the management of differentiated thyroid cancer, recommend adequate thyroid stimulating hormone (TSH) stimulation for radioactive (131)I administrations, both for imaging and subsequent ablations. Commonly followed method is to achieve this by endogenous TSH stimulation by withdrawal of thyroxine. Numerous studies worldwide have reported comparable results with recombinant human thyroid stimulating hormone (rhTSH) intervention as conventional thyroxine hormone withdrawal. Radiation safety applications call for the need to understand radioactive (131)I (RA(131)I) clearance pattern to estimate whole body doses when this new methodology is used in our institution. A study of radiation body burden estimation was undertaken in two groups of patients treated with RA(131)I; (a) one group of patients having thyroxine medication suspended for 5 weeks prior to therapy and (b) in the other group retaining thyroxine support with two rhTSH injections prior to therapy with RA(131)I. Sequential exposure rates at 1 m in the air were measured in these patients using a digital auto-ranging beta gamma survey instrument calibrated for measurement of exposure rates. The mean measured exposure rates at 1 m in μSv/h immediately after administration and at 24 h intervals until 3 days are used for calculating of effective ½ time of clearance of administered activity in both groups of patients, 81 patients in conventionally treated group (stop thyroxine) and 22 patients with rhTSH administration. The (131)I activities ranged from 2.6 to 7.9 GBq. The mean administered (131)I activities were 4.24 ± 0.95 GBq (n = 81) in "stop hormone" group and 5.11 ± 1.40 GBq (n = 22) in rhTSH group. The fall of radioactive body burden showed two clearance patterns within observed 72 h. Calculated T½eff values were 16.45 h (stop hormone group) 12.35 h (rhTSH group) for elapsed period of 48 h. Beyond 48 h post administration, clearance of RA(131)I takes place with T½eff> 20 h in both groups. Neck and stomach exposure rate measurements showed reduced uptakes in the neck for rhTSH patients compared with "stop thyroxine" group and results are comparable with other studies. Whole body clearance is faster for patients with rhTSH injection, resulting in less whole body absorbed doses, and dose to blood. These patients clear circulatory radioactivity faster, enabling them to be discharged sooner, thus reduce costs of the hospitalization. Reduction in background whole body count rate may improve the residual thyroid images in whole body scan. rhTSH provides TSH stimulation without withdrawal of thyroid hormone and hence can help patients to take up therapy without hormone deficient problems in the withdrawn period prior to RA(131)I therapy. This also will help in reducing the restriction time periods for patients to mix up with the general population and children.

Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland

PubMed Central

La Perle, Krista M.D.; Kim, Dong Chul; Hall, Nathan C.; Bobbey, Adam; Shen, Daniel H.; Nagy, Rebecca S.; Wakely, Paul E.; Lehman, Amy; Jarjoura, David

2013-01-01

Background Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine–induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of 123I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of 123I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake. Conclusions NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment. PMID:23441638

99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours.

PubMed

von Guggenberg, E; Dietrich, H; Skvortsova, I; Gabriel, M; Virgolini, I J; Decristoforo, C

2007-08-01

Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA(0),D: Glu(1)]minigastrin (DTPA-MG0) radiolabelled with (111)In and (90)Y, our group developed a (99m)Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC(0),D: Glu(1),desGlu(2-6)]minigastrin (HYNIC-MG11). (99m)Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. (99m)Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of (99m)Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. (99m)Tc-EDDA-HYNIC-MG11 shows advantages over (99m)Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement.

Volume reduction of benign thyroid nodules 3 months after a single treatment with high-intensity focused ultrasound (HIFU).

PubMed

Korkusuz, Huedayi; Fehre, Niklas; Sennert, Michael; Happel, Christian; Grünwald, Frank

2015-01-01

High-intensity focused ultrasound (HIFU) is a promising, non-invasive technique in treating benign thyroid nodules (TNs). The aim of this study was to evaluate the efficacy of HIFU to induce clinically meaningful shrinkage in benign predominantly solid TNs and to identify variables that influence or predict the magnitude of TN volume reduction. For each of ten subjects, HIFU treatment was conducted on a single nodule. Nodular volume was measured sonographically at baseline and at 3 months post-procedure. Nodular function and early treatment assessment was done scintigraphically. Median nodular volume reduction was 0.7 ml absolute and 48.8% relative to pre-interventional size (p < 0.05). Absolute shrinkage was negatively correlated with the average treatment depth (τ = -0.61, p < 0.05). Absolute nodular volume was positively correlated with the scintigraphic nodular uptake reduction (τ = 0.66, p < 0.05). HIFU treatment of benign predominantly solid TNs appears to be safe and effective for inducing nodular shrinkage. Despite potential for improvement, a single treatment session with HIFU is already a viable alternative to more standard methods. The feasibility of multiple HIFU treatments requires further investigation. Due to the small sample size, the findings of this analysis need conformation by larger studies.

Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury.

PubMed

Liu, Yan-Yun; Brent, Gregory A

2018-06-01

Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic alterations and neural death. In clinical studies, central hypothyroidism, due to hypothalamic and pituitary dysfunction, has been found in some individuals after brain injury. TH has been shown, in animal models, to be protective for the damage incurred from brain injury and may have a role to limit injury and promote recovery. Although clinical trials have not yet been reported, findings from in vitro and in vivo models inform potential treatment strategies utilizing TH for protection and promotion of recovery after brain injury. Published by Elsevier Inc.

Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice.

PubMed

Weiner, Juliane; Kranz, Mathias; Klöting, Nora; Kunath, Anne; Steinhoff, Karen; Rijntjes, Eddy; Köhrle, Josef; Zeisig, Vilia; Hankir, Mohammed; Gebhardt, Claudia; Deuther-Conrad, Winnie; Heiker, John T; Kralisch, Susan; Stumvoll, Michael; Blüher, Matthias; Sabri, Osama; Hesse, Swen; Brust, Peter; Tönjes, Anke; Krause, Kerstin

2016-12-12

The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal 18 F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo 14 C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. 18 F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced 18 F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively.

A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells

PubMed Central

Li, Guanhua; Hu, Zuojun; Yin, Henghui; Zhang, Yunjian; Huang, Xueling; Wang, Shenming; Li, Wen

2013-01-01

The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA) delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG) in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and gel retardation assay confirmed that complete triblock components were successfully synthesized with effective binding capacity of siRNA in this triblock nanocarrier. Cytotoxicity data indicated that conjugation of PEG significantly alleviated cytotoxicity when compared with unmodified PAMAM. PAMAM-PEG-cRGD exerted potent siRNA cellular internalization in which transfection efficiency measured by flow cytometry was up to 68% when the charge ratio (N/P ratio) was 3.5. Ligand-receptor affinity together with electrostatic interaction should be involved in the nano-siRNA endocytosis mechanism and we then proved that attachment of cRGD enhanced cellular uptake via RGD-integrin recognition. Gene silencing was evaluated by reverse transcription polymerase chain reaction and PAMAM-PEG-cRGD-siRNA complex downregulated the expression of hERG to 26.3% of the control value. Furthermore, gene knockdown of hERG elicited growth suppression as well as activated apoptosis by means of abolishing vascular endothelial growth factor secretion and triggering caspase-3 cascade in anaplastic thyroid carcinoma cells. Our study demonstrates that this novel triblock polymer, PAMAM-PEG-cRGD, exhibits negligible cytotoxicity, effective transfection, “smart” cancer targeting, and therefore is a promising siRNA nanocarrier. PMID:23569377

Tyrosine content, influx and accumulation rate, and catecholamine biosynthesis measured in vivo, in the central nervous system and in peripheral organs of the young rat. Influence of neonatal hypo- and hyperthyroidism.

PubMed

Diarra, A; Lefauconnier, J M; Valens, M; Georges, P; Gripois, D

1989-10-01

The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.

Uptake of N-nitrosodimethylamine (NDMA) from water by phreatophytes in the absence and presence of perchlorate as a co-contaminant.

PubMed

Yifru, Dawit D; Nzengung, Valentine A

2006-12-01

The uptake and fate of the emerging contaminants N-nitrosodimethylamine (NDMA) and perchlorate in phreatophytes was studied in a hydroponics system under greenhouse conditions. NDMA is a potent carcinogen, and perchlorate disrupts the functioning ofthe human thyroid gland. The rate of removal of NDMA from solution by rooted cuttings of black willow (Salix nigra) and hybrid poplar (Populus deltoides x nigra, DN34) trees varied seasonally, with faster removal in summer months when transpiration rates were highest. A linear correlation between the volume of water transpired and mass of NDMA removed from the root zone was observed, especially at higher NDMA concentrations. In bioreactors dosed with both NDMA (0.7-1.0 mg L(-1)) and perchlorate (27 mg L(-1)), no competitive uptake of NDMA and perchlorate was observed. While NDMA was primarily removed from solution by plant uptake, perchlorate was predominantly removed by rhizodegradation. In the presence of NDMA, a slower rate of rhizodegradation of perchlorate was observed, but still significantly faster than the rate of NDMA uptake. For experiments conducted with radiolabeled NDMA, 46.4 +/- 1.1% of the total 14C-activity was recovered in the plant tissues and 47.5% was phytovolatilized. The 46.4 +/- 1.1% recovered in the plants was distributed as follows: 18.8 +/- 1.4% in leaves, 15.9 +/- 5.9% in stems, 7.6 +/- 3.2% in branches, and 3.5 +/- 3.3% in roots. The poor extractability of NDMA with methanol-water (1:1 v/v) from stem and leaf tissues suggested that some fraction of NDMA was assimilated. The calculated transpiration stream concentration factor (TSCF) of 0.28 +/- 0.06 suggests that NDMA is passively taken up by phreatophytes, and mainly phytovolatilized.

Flexible mini gamma camera reconstructions of extended sources using step and shoot and list mode.

PubMed

Gardiazabal, José; Matthies, Philipp; Vogel, Jakob; Frisch, Benjamin; Navab, Nassir; Ziegler, Sibylle; Lasser, Tobias

2016-12-01

Hand- and robot-guided mini gamma cameras have been introduced for the acquisition of single-photon emission computed tomography (SPECT) images. Less cumbersome than whole-body scanners, they allow for a fast acquisition of the radioactivity distribution, for example, to differentiate cancerous from hormonally hyperactive lesions inside the thyroid. This work compares acquisition protocols and reconstruction algorithms in an attempt to identify the most suitable approach for fast acquisition and efficient image reconstruction, suitable for localization of extended sources, such as lesions inside the thyroid. Our setup consists of a mini gamma camera with precise tracking information provided by a robotic arm, which also provides reproducible positioning for our experiments. Based on a realistic phantom of the thyroid including hot and cold nodules as well as background radioactivity, the authors compare "step and shoot" (SAS) and continuous data (CD) acquisition protocols in combination with two different statistical reconstruction methods: maximum-likelihood expectation-maximization (ML-EM) for time-integrated count values and list-mode expectation-maximization (LM-EM) for individually detected gamma rays. In addition, the authors simulate lower uptake values by statistically subsampling the experimental data in order to study the behavior of their approach without changing other aspects of the acquired data. All compared methods yield suitable results, resolving the hot nodules and the cold nodule from the background. However, the CD acquisition is twice as fast as the SAS acquisition, while yielding better coverage of the thyroid phantom, resulting in qualitatively more accurate reconstructions of the isthmus between the lobes. For CD acquisitions, the LM-EM reconstruction method is preferable, as it yields comparable image quality to ML-EM at significantly higher speeds, on average by an order of magnitude. This work identifies CD acquisition protocols combined with LM-EM reconstruction as a prime candidate for the wider introduction of SPECT imaging with flexible mini gamma cameras in the clinical practice.

Hepatic OATP Transporter and Thyroid Hormone Receptor Interplay Determines Cholesterol and Glucose Homeostasis

PubMed Central

Meyer zu Schwabedissen, Henriette E.; Ware, Joseph A.; Finkelstein, David; Chaudhry, Amarjit S.; Lemay, Sara; Leon-Ponte, Matilde; Strom, Stephen C.; Zaher, Hani; Schwarz, Ute I.; Freeman, David J.; Schuetz, Erin G.; Tirona, Rommel G.; Kim, Richard B.

2011-01-01

The role of Organic Anion Transporting Polypeptides (OATPs), particularly the members of OATP1B-subfamily, in hepatocellular handling of endogenous and exogenous compounds is an important and emerging area of research. Using a mouse model lacking Slco1b2, the murine ortholog of the OATP1B-subfamily, we previously demonstrated that genetic ablation causes reduced hepatic clearance capacity for substrates. In this report we focused on the physiological function of the hepatic OATP1B transporters. First we studied the influence of the Oatp1b2 deletion on bile acid metabolism showing that lack of the transporter results in a significantly reduced expression of Cyp7a1 the key enzyme of bile acid synthesis, resulting in elevated cholesterol levels after high dietary fat challenge. Furthermore, Slco1b2−/− mice exhibited delayed clearance after oral glucose challenge resulting from reduced hepatic glucose uptake. In addition to increased hepatic glycogen content, Slco1b2−/−exhibited reduced glucose output after pyruvate challenge. This is in accordance with reduced hepatic expression of PEPCK in knockout mice. We show this phenotype is due to the loss of liver-specific Oatp1b2-mediated hepatocellular thyroid hormone entry, which then leads to reduced transcriptional activation of target genes of hepatic thyroid hormone receptor (TR) including the prior mentioned Cyp7a1 and Pepck, but also Dio1 and Glut2. Importantly, we assessed human relevance using a cohort of archived human livers where OATP1B1 expression was noted to be highly associated with TR target genes, especially for GLUT2. Furthermore, GLUT2 expression was significantly decreased in livers harboring a common genetic polymorphism in SLCO1B1. Conclusion Our findings reveal that OATP1B-mediated hepatic thyroid hormone entry is a key determinant of cholesterol and glucose homeostasis. PMID:21538436

Thyroid Lobe Ablation with Radioactive Iodine as an Alternative to Completion Thyroidectomy After Hemithyroidectomy in Patients with Follicular Thyroid Carcinoma: Long-Term Follow-Up

PubMed Central

Goldfarb, Melanie; Parangi, Sareh; Yang, Jingyun; Ross, Douglas S.; Daniels, Gilbert H.

2012-01-01

Background Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC. Methods This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with 131I (30–32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were 131I uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival. Results After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T-Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group (p<0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease (p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL were found in 87.5% of the RAI-L-ABL group (n=28), 86.3% of the C-Tx group (n=57), and 77.8% of the T-Tx group (n=21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p<0.05, between groups). Conclusions RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of >25 mIU/L and preparing patients for conventional 131I treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2–2.2 ng/mL) is more common after RAI-L-ABL. PMID:22385290

Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study.

PubMed

Liu, Chien-Liang; Cheng, Shih-Ping; Lin, Hui-Wen; Lai, Yuen-Liang

2014-03-01

The causative relationship between autoimmune thyroiditis and thyroid cancer remains a controversial issue. The aim of this population-based study was to investigate the risk of thyroid cancer in patients with thyroiditis. From the Longitudinal Health Insurance Database 2005 (LHID2005) of Taiwan, we identified adult patients newly diagnosed with thyroiditis between 2004 and 2009 (n = 1,654). The comparison cohort (n = 8,270) included five randomly selected age- and sex-matched controls for each patient in the study cohort. All patients were followed up from the date of cohort entry until they developed thyroid cancer or to the end of 2010. Multivariate Cox regression was used to assess the risk of developing thyroid cancer. A total of 1,000 bootstrap replicates were created for internal validation. A total of 35 patients developed thyroid cancer during the study period, of whom 24 were from the thyroiditis cohort and 11 were from the comparison cohort (incidence 353 and 22 per 100,000 person-years, respectively). After adjusting for potential confounding factors, the hazard ratio (HR) for thyroid cancer in patients with thyroiditis was 13.24 (95 % CI 6.40-27.39). Excluding cancers occurring within 1 year of follow-up, the HR remained significantly increased (6.64; 95 % CI 2.35-18.75). Hypothyroidism was not an independent factor associated with the occurrence of thyroid cancer. We found an increased risk for the development of thyroid cancer after a diagnosis of thyroiditis, independent of comorbidities.

The natural history of thyroid autonomy and hot nodules.

PubMed

Corvilain, B

2003-02-01

Solitary hyperfunctioning thyroid adenomas are benign monoclonal tumors characterized by their capacity to grow and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the absence of thyrotropin (TSH). Mutations of the TSH receptor (TSH-R) have been found in the majority of solitary hyperfunctioning thyroid adenomas. On radioisotope scanning they generally appear as hot nodules because they concentrate radioiodide or 99mTc pertechnate, whereas the normal surrounding and contralateral tissue concentrate little isotopes. A toxic adenoma probably evolves gradually from a small autonomously hyperfunctioning adenoma that initially is only slightly more active than the extranodular tissue. This has been referred to as a "warm" nodule or a "compensated" adenoma. The diagnostic criterion for this designation is the persistence of detectable serum TSH maintaining some radioiodine uptake by the extranodular tissue. This "compensated" adenoma persists as long as the autonomous hormone output is not sufficient to suppress thyrotropin, i.e. to cause hyperthyroidism. The rate of development of thyrotoxicosis in patients with hyperfunctioning adenomas who are euthyroid initially is about 4% per year and depends on the size of the adenoma, iodine intake and age of the patient. No clear relationship can be establish between the nature of the TSH receptor mutations and the phenotype of the tumor.

Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.

PubMed

Kitahara, Cari M; K Rmendiné Farkas, Dóra; Jørgensen, Jens Otto L; Cronin-Fenton, Deirdre; Sørensen, Henrik Toft

2018-06-01

Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Nationwide (Denmark). Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.

Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS).

PubMed

Dadachova, E; Bouzahzah, B; Zuckier, L S; Pestell, R G

2002-01-01

The sodium-iodide symporter (NIS), which transports iodine into the cell, is expressed in thyroid tissue and was recently found to be expressed in approximately 80% of human breast cancers but not in healthy breast tissue. These findings raised the possibility that therapeutics targeting uptake by NIS may be used for breast cancer treatment. To increase the efficacy of such therapy it would be ideal to identify a radioactive therapy with enhanced local emission. The feasibility of using the powerful beta-emitting radiometal (188)Re in the form of (188)Re-perrhenate was therefore compared with 131I for treatment of NIS-expressing mammary tumors. In the current studies, using a xenografted breast cancer model induced by the ErbB2 oncogene in nude mice, (188)Re-perrhenate exhibited NIS-dependent uptake into the mammary tumor. Dosimetry calculations in the mammary tumor demonstrate that (188)Re-perrhenate is able to deliver a dose 4.5 times higher than (131)I suggesting it may provide enhanced therapeutic efficacy.

Role of PET in medullary thyroid carcinoma.

PubMed

Rufini, V; Treglia, G; Perotti, G; Leccisotti, L; Calcagni, M L; Rubello, D

2008-06-01

In the diagnostic assessment of medullary thyroid carcinoma (MTC), nuclear medicine imaging provides its contribution mainly in the postoperative work-up to detect residual or recurrent tumor. With respect to scintigraphy with gamma-emitter radiopharmaceuticals, positron emission tomography (PET) offers interesting perspectives owing to its higher image quality, spatial resolution and speed. Moreover, the recent developments of hybrid machines allow to obtain images that simultaneously hold both anatomic (computed tomography) and functional (PET) information with great impact on diagnostic efficacy. (18)F-fluoro-deoxyglucose ((18)F-FDG) is the most frequently used PET tracer in oncology. Preliminary reports of FDG-PET in MTC patients show encouraging results with a higher sensitivity in detecting local recurrent and metastatic disease when compared with single photon emission tracers. However, (18)F-FDG uptake depends on lesion size and to some extent on the grade of differentiation and biologic aggressiveness of the tumor; so FDG-PET seems useful mainly in patients with very high calcitonin levels and high progression rate. Like other neuroendocrine tumors, MTC is characterized by the presence of amine uptake mechanism and/or peptide receptors at the cell membrane allowing the clinical use of specific radiopharmaceuticals that reflect the different metabolic pathways of MTC, and in particular the synthesis, storage and release of hormones ((18)F-dihydroxyphenilalanine, (18)F-DOPA and (18)F-fluorodopamine, (18)F-FDA) and the expression of receptors ((68)Ga-labeled somatostatin analogs). These tracers are currently under investigation and will further improve the diagnostic approach of MTC.

Concerns with low-level ionizing radiation.

PubMed

Yalow, R S

1994-05-01

To clarify the effects of ionizing radiation and to dispel fear associated with the use of radioactivity in medical diagnosis and therapy. Studies of populations in geographic areas of increased cosmic radiation and high natural background radiation, radiation-exposed workers, patients with medical exposure to radioactivity, and accidental exposure are reviewed. No reproducible evidence shows harmful effects associated with increases in background radiation of 3 to 10 times the usual levels. American military personnel who participated in nuclear testing had no increase in leukemia or other cancers. Among 22,000 patients with hyperthyroidism treated with 131I (mean dose, 10 rem), no increased incidence of leukemia was found in comparison with 14,000 similar patients who received other treatment. A 20-year follow-up of 35,000 patients who underwent 131I uptake tests for evaluation of thyroid function revealed that those studied for other than a suspected tumor had only 60% of the thyroid cancers expected in a control group. Although early studies showed that high exposures to miners to radon and its daughters resulted in a substantial increase in lung cancer, no evidence exists for an increase in lung cancer among nonsmokers exposed to increased radon levels in the home. Perhaps the association of radiation with the atomic bomb has created a climate of fear about the possible dangers of radiation at any level; however, no evidence indicates that current radiation exposures associated with medical usage are harmful.

Radiometabolic treatment of hyperthyroidism with a calculated dose of 131-iodine: results of one-year follow-up.

PubMed

Regalbuto, C; Marturano, I; Condorelli, A; Latina, A; Pezzino, V

2009-02-01

Oral administration of radioactive iodine (131I) is a well-known and effective procedure for the treatment of hyperthyroidism. However, the optimal dose is still a matter of debate, as is the frequency of recurrence and hypothyroidism. The aim of our study was to evaluate the 1-yr outcome of a calculated dose of 131I activity in the treatment of hyperthyroidism, following the guidelines published jointly by the Italian Society of Endocrinology and the Italian Society of Nuclear Medicine.We studied 84 patients affected with hyperthyroidism (55 with Graves' disease and 29 with toxic adenoma), who were treated with a dose of 131I activity obtained by using the formula from the guidelines. In all patients serum free T4, free T3, and TSH were measured before, and 2, 6, and 12 months after radiometabolic therapy. A thyroid scan and thyroid uptake with 131I were also performed before treatment, and a thyroid ultrasound scan was obtained before and 1 yr after treatment. One year after treatment, 22 out of 55 patients with Graves' diseases (40.0%) had persistence/ recurrence of hyperthyroidism, whereas only 1 patient of the 29 with toxic adenoma (3.4%) was still in a hyperthyroid state. The frequency of hypothyroidism in patients responsive to therapy was higher in subjects with Graves' disease (45.5%), than in those with toxic adenoma (17.3%, p=0.02). Overall size reduction of the target lesion was 56.2+/-23.1%. In conclusion, the dose calculation suggested by the guidelines represents an effective method for treating thyroid toxic adenoma. In subjects with Graves' disease, we propose using a pre-determined 131I activity, which is higher than that derived from the guidelines. Such an approach would reduce the incidence of recurrent/persistent hyperthyroidism. On the other hand, an increase in post-131I hypothyroidism should not be regarded as a negative effect in these patients, since hypothyroidism is easily corrected, and the risk of worsening ophthalmopathy is reduced.

Errors in the absorbed and the administered 131I therapeutic dose in patients with Graves' disease. A suggested more precise technique.

PubMed

Chen, Yangchun; Huang, Jincheng; Wang, Yuehui; Xie, Sipei; He, Fang

2017-01-01

The aim of this study was to evaluate the relative error (RE) in the thyroid absorbed dose (TD) of iodine-131 ( 131 I) in patients with Graves' disease comparing the simplified Quimby-Marinelli-Hine formula method (sQMHF) and the Standard Operational Procedures for dosimetry (SOPD) recommended by the European Association of Nuclear Medicine. This study included 45 patients with Graves' disease 12 men and 33 women; age 44.1±12.8 years. Thyroid mass (TM) was measured using ultrasound. Uptake of 131 I (RAIU) was tested at 2, 4-6, 24, 48-72, and 96-168h after its administration and the half-life (T 1/2eff ) and resident time (RT) of 131 I were computed. According to the sQMHF, a prescribed TD of 75Gy required 3.7MBq/g of 131 I, correction based on the RAIU 24h and T 1/2eff . Subsequently, the therapeutic TD was computed according to the SOPD and the RE was recorded. The data were analyzed using t-tests. The TM, RAIU 24h , therapeutic TD, and RE were 36.5±23.9g, 0.54±0.14, 89.4±9.4Gy, and -0.01±0.02, respectively. There was a significant difference (t-value 9.84, P<0.01) between the prescribed and therapeutic TD because the sQMHF ignores the absorbed dose deposited in the thyroid during the first 24h, which is included in the SOPD. In addition, the RE was significantly smaller than the variable coefficient (VC) of the therapeutic TD (t=-39.6, P<0.01). When the activity of 131 I was calculated using the simplified Q-M-H formula, the therapeutic absorbed thyroid dose was significantly higher than what was expected for the prescribed dose. Precision of the individualized therapeutic absorbed dose could be improved by computing the activity of 131 I using the standard operational procedures for dosimetry of the EANM.

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects

PubMed Central

Singhal, Neha; Praveen, V. P.; Bhavani, Nisha; Menon, Arun S.; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R. V.; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Context: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. Aim: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Subjects and Methods: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Statistical Analysis Used: Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Results: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). Conclusion: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease. PMID:27042408

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

PubMed

Singhal, Neha; Praveen, V P; Bhavani, Nisha; Menon, Arun S; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R V; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

Biokinetics and dosimetric studies about 99mTc(V)-DMSA distribution.

PubMed

Correia, M B L; Magnata, S S L P; Silva, I M S; Catanho, M T J A; Lima, F F

2010-05-10

Research for radiodiagnostic agents should considerate biological critical parameters which will give own contribution on the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with (99m)Tc(V) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in evaluation of bone metastasis. This work studied the biokinetics and dosimetry of (99m)Tc(V)-DMSA by animal model. The (99m)Tc(V)-DMSA was prepared from a (III)DMSA kit alkalized. Mice (n=5) received (99m)Tc(V)DMSA i.v., they were sacrificed (30 min, 1h, 5h and 12h), the organs excised and the activities measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated (MIRDOSE 3.0 program) by extrapolation of data from animal to human scale. The results showed the majority of organs reached the top uptake at 30 min, the greatest kidney uptake was (4.81 +/- 1.38)% activity/g, while the bone presented its highest uptake at 1h (5.49+/- 0.47)% activity/g, after 1h all the organs had activity exponential decrease. The biokinetic profile of (99m)Tc(V)-DMSA was well established, allowing quantifying of residence time, and the radiation dose estimates were made for this agent. About the absorbed dose, the preliminary results showed higher value to bone, being the soft tissue dose relatively low.

Radioiodine treatment of hyperthyroidism in a pregnant women.

PubMed

Berg, G E; Nyström, E H; Jacobsson, L; Lindberg, S; Lindstedt, R G; Mattsson, S; Niklasson, C A; Norén, A H; Westphal, O G

1998-02-01

We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

Imaging of Prostate-Specific Membrane Antigen Expression in Metastatic Differentiated Thyroid Cancer Using 68Ga-HBED-CC-PSMA PET/CT.

PubMed

Lütje, Susanne; Gomez, Benedikt; Cohnen, Joseph; Umutlu, Lale; Gotthardt, Martin; Poeppel, Thorsten D; Bockisch, Andreas; Rosenbaum-Krumme, Sandra

2017-01-01

The prostate-specific membrane antigen (PSMA) was shown to be overexpressed on the neovasculature of several malignancies. Here, the role of Ga-HBED-CC-PSMA PET/CT for the detection of PSMA expression in patients with metastasized differentiated thyroid cancer (DTC) was evaluated. Six patients with iodine-negative and F-FDG-positive metastasized DTC (mean TG, 1616 ng/mL) received 71-93 MBq of the Ga-labeled PSMA ligand and underwent PET/CT at 62 ± 7 minutes p.i.. Tumor accumulation capacity of the tracer and the detection rate of local recurrences and metastases were compared with F-FDG. Tracer uptake was quantified in terms of the SUVmax. In 5 of 6 patients, sites of putative metastatic disease could be identified using Ga-HBED-CC-PSMA PET/CT. All lesions detected with Ga-HBED-CC-PSMA PET/CT (n = 42) were confirmed by F-FDG PET/CT or conventional CT imaging. Using Ga-HBED-CC-PSMA PET/CT, all tumor lesions identified with F-FDG PET/CT imaging could be visualized in 3 of 5 patients. In 2 patients, only the most prominent lesions detected with F-FDG PET/CT imaging were visualized by Ga-HBED-CC-PSMA PET/CT. Ga-HBED-CC-PSMA uptake ranged from low in 1 patient (mean SUVmax 3.3) to intermediate (1 patient; mean SUVmax, 6.1) to intense (3 patients; mean SUVmax, 12.8, 16.2, and 18.3). The highest SUVmax values were observed for a bone lesion, reaching 39.7. These preliminary results indicate that Ga-HBED-CC-PSMA PET/CT might be suitable for staging of patients with metastasized DTC. Ga-HBED-CC-PSMA PET/CT could be useful for the identification of patients who might qualify for PSMA-targeted radionuclide therapy because of high PSMA uptake.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Assessment of Minimum 124I Activity Required in Uptake Measurements Before Radioiodine Therapy for Benign Thyroid Diseases.

PubMed

Gabler, Anja S; Kühnel, Christian; Winkens, Thomas; Freesmeyer, Martin

2016-08-01

This study aimed to assess a hypothetical minimum administered activity of (124)I required to achieve comparability between pretherapeutic radioiodine uptake (RAIU) measurements by (124)I PET/CT and by (131)I RAIU probe, the clinical standard. In addition, the impact of different reconstruction algorithms on (124)I RAIU and the evaluation of pixel noise as a parameter for image quality were investigated. Different scan durations were simulated by different reconstruction intervals of 600-s list-mode PET datasets (including 15 intervals up to 600 s and 5 different reconstruction algorithms: filtered-backprojection and 4 iterative techniques) acquired 30 h after administration of 1 MBq of (124)I. The Bland-Altman method was used to compare mean (124)I RAIU levels versus mean 3-MBq (131)I RAIU levels (clinical standard). The data of 37 patients with benign thyroid diseases were assessed. The impact of different reconstruction lengths on pixel noise was investigated for all 5 of the (124)I PET reconstruction algorithms. A hypothetical minimum activity was sought by means of a proportion equation, considering that the length of a reconstruction interval equates to a hypothetical activity. Mean (124)I RAIU and (131)I RAIU already showed high levels of agreement for reconstruction intervals of as short as 10 s, corresponding to a hypothetical minimum activity of 0.017 MBq of (124)I. The iterative algorithms proved generally superior to the filtered-backprojection algorithm. (124)I RAIU showed a trend toward higher levels than (131)I RAIU if the influence of retrosternal tissue was not considered, which was proven to be the cause of a slight overestimation by (124)I RAIU measurement. A hypothetical minimum activity of 0.5 MBq of (124)I obtained with iterative reconstruction appeared sufficient both visually and with regard to pixel noise. This study confirms the potential of (124)I RAIU measurement as an alternative method for (131)I RAIU measurement in benign thyroid disease and suggests that reducing the administered activity is an option. CT information is particularly important in cases of retrosternal expansion. The results are relevant because (124)I PET/CT allows additional diagnostic means, that is, the possibility of performing fusion imaging with ultrasound. (124)I PET/CT might be an alternative, especially when hybrid (123)I SPECT/CT is not available. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PREVALENCE OF AUTOIMMUNE THYROIDITIS AND THYROID DYSFUNCTION IN HEALTHY ADULT MEXICANS WITH A SLIGHTLY EXCESSIVE IODINE INTAKE.

PubMed

Flores-Rebollar, Armando; Moreno-Castañeda, Lidia; Vega-Servín, Norman S; López-Carrasco, Guadalupe; Ruiz-Juvera, Aída

2015-08-01

the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital's medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti-peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P = 0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 μg/L, (IQR 161.3 - 482.5). in spite of our study's limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

PubMed Central

Vicari, Luisa; Musumeci, Teresa; Giannone, Ignazio; Adamo, Luana; Conticello, Concetta; De Maria, Ruggero; Pignatello, Rosario; Puglisi, Giovanni; Gulisano, Massimo

2008-01-01

Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested. Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies. PMID:18657273

The increased risk of globus pharyngeus in patients with chronic thyroiditis: a case control study.

PubMed

Karahatay, S; Ayan, A; Aydin, U; Ince, S; Emer, O; Alagoz, E

2015-12-01

A correlation between globus pharyngeus and thyroid gland inflammation has been mentioned in previous studies. However, the potential risk of globus pharyngeus in chronic thyroiditis patients has not been shown so far. The aim of this study is to investigate a possible association between chronic thyroiditis and globus pharyngeus. The study was performed in an ultrasound (US) center of a tertiary health care institution. Ninety-two patients who were under examination for suspected thyroid pathologies or undergoing follow-up for a previously diagnosed thyroid disease were enrolled in the study. The patients were divided into two groups according to the existence of globus symptoms. Subsequently, all patients underwent high-resolution thyroid ultrasounds. The patients whose ultrasound findings were suggestive of chronic thyroiditis constituted the second subgroup. The demographic data of the patients and other ultrasound findings including the volume of the thyroid glands and nodules, if any, were noted as well. Sixty-seven female (73%) and 25 male (27%) patients were enrolled in the study. Thirty-two (35%) of the 92 patients constituted the globus pharyngeus group according to their responses to the questionnaire and the US findings were concordant with chronic thyroiditis in 36 (39%) patients. The correlation between chronic thyroiditis and globus sensation was significant (p = 0.004), and the odds ratio was calculated as 3.7 (95% CI = 1.5-9.11). Other parameters including age, sex, thyroid volume and nodule status were not significantly related to globus pharyngeus in this particular patient series. In the presented study, the risk of globus pharyngeus occurrence was calculated as 3.7-fold higher in patients with chronic thyroiditis. Being a preliminary report, it is necessary to confirm this finding and understand the pathophysiological mechanism via further investigations with a larger patient series.

Age impact on autoimmune thyroid disease in females

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

Cancer.gov

In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

Thyroid function and obesity.

PubMed

Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

2012-10-01

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.

Incidental Warthin Tumor on Pertechnetate Scintigraphy.

PubMed

Kulkarni, Mukta; Shetkar, Shubhangi; Joshi, Prathamesh; Kasaliwal, Sanket; Chaudhari, Shrikant

2016-09-01

A 30-year-old woman underwent Tc-pertechnetate scintigraphy for evaluation of thyrotoxicosis. The scintigraphy revealed hypervascular thyroid gland with markedly increased trapping function in both the lobes suggesting diagnosis of Graves disease. Incidentally, a hypervascular and pertechnetate avid focus was seen along the lateral margin of the right parotid gland. Pertechnetate avidity and site of uptake suggested possibility of Warthin tumor. Clinical examination and ultrasonography revealed a well-defined lesion in the superficial lobe of the right parotid gland favoring diagnosis of benign lesion. Postsurgery specimen confirmed diagnosis of Warthin tumor.

The Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.

PubMed

Norström, Fredrik; van der Pals, Maria; Myléus, Anna; Hammarroth, Solveig; Högberg, Lotta; Isaksson, Anders; Ivarsson, Anneli; Carlsson, Annelie

2018-01-25

Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. However, data are lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1,695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid stimulating hormone and free thyroxine. TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were: 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicate that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

Influence of cigarette smoking on thyroid gland--an update.

PubMed

Sawicka-Gutaj, Nadia; Gutaj, Paweł; Sowiński, Jerzy; Wender-Ożegowska, Ewa; Czarnywojtek, Agata; Brązert, Jacek; Ruchała, Marek

2014-01-01

Many studies have shown that cigarette smoking exerts multiple effects on the thyroid gland. Smoking seems to induce changes in thyroid function tests, like decrease in TSH and increase in thyroid hormones. However, these alterations are usually mild. In addition, tobacco smoking may also play a role in thyroid autoimmunity. Many studies have confirmed a significant influence of smoking on Graves' hyperthyroidism and particularly on Graves' orbitopathy. Here, smoking may increase the risk of disease development, may reduce the effectiveness of treatment, and eventually induce relapse. The role of smoking in Hashimoto's thyroiditis is not as well established as in Graves' disease. Nonetheless, lower prevalence of thyroglobulin antibodies, thyroperoxidase antibodies and hypothyroidism were found in smokers. These findings contrast with a study that reported increased risk of hypothyroidism in smokers with Hashimoto's thyroiditis. Moreover, cigarette smoking increases the incidence of multinodular goitre, especially in iodine-deficient areas. Some studies have examined cigarette smoking in relation to the risk of thyroid cancer. Interestingly, many of them have shown that smoking may reduce the risk of differentiated thyroid cancer. Furthermore, both active and passive smoking during pregnancy might modify maternal and foetal thyroid function. This review evaluates the current data concerning the influence of cigarette smoking on thyroid gland, including hormonal changes, autoimmunity and selected diseases. These findings, however, in our opinion, should be carefully evaluated and some of them are not totally evidence-based. Further studies are required to explain the effects of smoking upon thyroid pathophysiology.

Comparison of the symptoms of menopause and symptoms of thyroid disease in Japanese women aged 35-59 years.

PubMed

Oi, N; Ohi, K

2013-10-01

In this study, we surveyed thyroid function abnormalities and menopausal symptoms in young as well as in menopausal women. We conducted a random survey among outpatients at our facility from September 2008 to June 2011. The study included 853 women aged 35-59 years. We assessed the subjects according to the Simplified Menopause Index, menstrual status, thyroid hormone measurements (thyroid stimulating hormone, free thyroxine, free triiodothyronine), the presence of Hashimoto's disease antibodies (anti-thyroid peroxidase antibody or anti-thyroglobulin antibody), the presence of Grave's disease (anti-TSH receptor antibody), markers of thyroid tumor (high thyroglobulin), and thyroid ultrasonography studies. The data were analyzed by means of the statistical program JMP version 8.0. 'Facial flushing', 'sweating', and 'thyroid tumor' were all positively related with age and menstrual status. 'Breathlessness and palpitations' were positively related to Grave's disease. Moreover, 'sweating', 'irritability', and 'stiff shoulders, low back pain, and joint pain' were related to thyroid tumors. 'Insomnia' decreased with age. Patients with Hashimoto's disease were very rare because they were usually treated at other hospitals that specialize in thyroid disease. The symptoms of thyroid function abnormalities were shown to be very similar to menopausal symptoms and were found to occur in younger women before the onset of menopause. This study shows the need to differentiate menopausal symptoms from those of thyroid diseases.

Etiopathologic findings of canine hypothyroidism.

PubMed

Graham, Peter A; Refsal, Kent R; Nachreiner, Raymond F

2007-07-01

The causes of canine hypothyroidism are varied, but most cases result from irreversible acquired thyroid pathologic changes and only a small proportion arise from congenital anomalies of the thyroid gland or pituitary. Of primary thyroid failure, at least half is the result of immune-mediated thyroiditis. Recent research has focused on the genetics and immunology of canine thyroid disease, adding to what is known from experimental and human studies. Epidemiologic and diagnostic laboratory studies continue to provide information on contributing factors and raise questions for future research directions. Serum antibodies against thyroid components are common in thyroid pathologic conditions and dysfunction, and understanding their properties and frequency is important in the interpretation of thyroid diagnostic test results.

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

PubMed Central

Anderson, Grant; Forrest, Douglas; Galton, Valerie Anne; Gereben, Balázs; Kim, Brian W.; Kopp, Peter A.; Liao, Xiao Hui; Obregon, Maria Jesus; Peeters, Robin P.; Refetoff, Samuel; Sharlin, David S.; Simonides, Warner S.; Weiss, Roy E.; Williams, Graham R.

2014-01-01

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes. PMID:24001133

Co-Existence of Thyroid Nodule and Thyroid Cancer in Children and Adolescents with Hashimoto Thyroiditis: A Single-Center Study.

PubMed

Keskin, Meliksah; Savas-Erdeve, Senay; Aycan, Zehra

2016-01-01

Currently, there is an inadequate number of studies on nodule and malignancy development in children and adolescents with Hashimoto thyroiditis (HT). Patients who were diagnosed with HT between 2004 and 2013 were included in the study. The HT diagnosis was made with a heterogeneous appearance on thyroid ultrasonography and the elevation of antithyroid peroxidase and/or anti-thyroglobulin antibodies. Fine-needle aspiration biopsy (FNAB) was performed in cases with a nodule size >1 cm or who had ultrasonography findings indicating malignancy. A total of 39 (13%) thyroid nodules were detected in 300 patients with a diagnosis of HT. Papillary thyroid carcinoma (PTC) was diagnosed in 2 of the 12 cases in whom FNAB was performed. The thyroid nodule was detected at the same time as HT in the 2 cases with malignancy. The PTC diagnosis was made 2 years after the HT diagnosis in the first case and 3 years later in the second case. The largest diameter of the thyroid nodule was 5 mm in both cases. The thyroid nodule rate on an HT background was found to be 13%, and the thyroid malignancy rate was 0.67% in our study. © 2016 S. Karger AG, Basel.

Long term studies of the rat reticuloendothelial system and endocrine gland responses to foreign particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frankel, Howard H.; Patek, Paul R.; Bernick, Sol

1962-03-01

Changes in morphology and responses of macrophages to a single intravenous injection of carbon or thorium dioxide (Thorotrast) were studied in rats. Localization of C particles is described in detail, although an identical response of macrophages to ThO 2 was observed. In lever, C particles were observed in Kupffer cells lining the sinusoids of the hepatic lobule 24 hr after injection. At 48 hr the concentration of C increased within the hepatic lobule. The increased uptake of C by individual Kupffer cells eventually led to conglomeration of these macrophages and apparent sinusoidal occlusion. Only a minimal amount of C particlesmore » was observed in the lungs at one month, but migration of Claden macrophages to lung from liver began one month after the injection and quickly ceased shortly afterward. There was a relative increase in the particles demonstrated in the spleen as the experiment progressed. Administration of the reticuloendothelial blocking agents resulted in morphological changes in the thyroid gland, anterior pituitary, and adrenals. Both C and ThO 2 produced a hyperplasia of the thyroid follicles. Concomitantly, there was a marked increase in the number of thyrotrophic cells of the anterior pituitary, suggesting thyrotropin production or release. There was also an increased infiltration of a sudanophilic positive substance into all the zones of the adrenal cortex. (H.H.D.)« less

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

Hwang, T. S.; Park, S. H.

1988-01-01

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis. PMID:3079564

Neck and whole-body scanning with 5-mCi dose of (123)I as diagnostic tracer in patients with well-differentiated thyroid cancer.

PubMed

Gulzar, Z; Jana, S; Young, I; Bukberg, P; Yen, V; Naddaf, S; Abdel-Dayem, H M

2001-01-01

To determine whether a 5-mCi dose of 123I can be used as an effective radiotracer for assessing the presence of remnant thyroid tissue and for searching for metastatic lesions in patients with well-differentiated thyroid cancer as well as to attempt to ascertain whether a scan performed only at 4 hours is sufficient for accurate diagnosis and might replace the conventional protocol of scanning at both 4 hours and 24 hours. We prospectively studied 27 patients who had undergone near-total thyroidectomy and had a documented diagnosis of well-differentiated thyroid carcinoma. Patients underwent scanning after receiving a 5-mCi dose of 123I, at a time when they had discontinued thyroid replacement therapy and had a thyrotropin level in excess of 30 mIU/mL. Whole-body images at 4 hours and 24 hours were obtained and were compared with posttherapy scans obtained 5 to 7 days after administration of 131I. Scans were interpreted by two board-certified nuclear medicine physicians. Of the 27 patients, 2 (7.4%) showed discordance between the 123I scan performed at 24 hours and the posttherapy 131I scan. When 4-hour images after administration of 123I were compared with the posttherapy 131I scans, a discordance rate of 14.8% (4 of 27 patients) was noted. In addition, two of these four patients showed lesions on the 24-hour images that were not seen on the 4-hour images (one with new lung metastatic involvement and the other with a local recurrence in the lower neck area). The prognosis and treatment of these two patients were substantially changed by the result of the 24-hour images. On comparison of scans obtained after administration of a 5-mCi dose of 123I with those obtained after 131I therapy, we conclude that 5 mCi of 123I produces images that have excellent quality and resolution and also compare favorably with those obtained after 131I therapy. Furthermore, a decrease in the dose of 123I from 10 mCi to 5 mCi lowered the cost of the study without compromising the diagnostic accuracy or image quality. Finally, use of 24-hour images will occasionally disclose additional areas of radioiodine uptake not detected on the 4-hour scans and is therefore recommended.

The association between thyroid malignancy and chronic lymphocytic thyroiditis: should it alter the surgical approach?

PubMed

Büyükaşık, Oktay; Hasdemir, Ahmet Oğuz; Yalçın, Erol; Celep, Bahadır; Sengül, Serkan; Yandakçı, Kemal; Tunç, Gündüz; Küçükpınar, Tevfik; Alkoy, Seval; Cöl, Cavit

2011-01-01

The relation between thyroid neoplasms and chronic lymphocytic thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic thyroiditis develops secondarily to malignancy, it is not clear whether diffuse lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of this study was to investigate the relation between CLT and malignant tumours of the thyroid and evaluate the surgical approach to CLT cases. In this study, 917 patients operated on for thyroid diseases were investigated retrospectively. Seventy-seven (8.4%) patients histopathologically diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT and thyroid malignancy were coexisting were included in the study. In the pathological evaluation of 917 cases, malignancy in the thyroid was found in 97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16 (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%) medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of malignancy against the background of CLT was 19.48%, while the rate in the groups without CLT was 9.76%, with a statistically significant difference between the groups (p = 0.008). CLT cases should be evaluated more carefully in terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical intervention should be lobectomy. Total thyroidectomy should be considered as preferable to subtotal thyroidectomy because of its many advantages such as controlling thyroiditis, removing the probability of reoperation, and hormonal stability.

Thyroid nodules in the population living around Semipalatinsk nuclear test site: possible implications for dose-response relationships study.

PubMed

Zhumadilov, Zhaxybay

2006-02-01

The risk of radiation-induced nodules is higher than the risk for radiation-induced cancer. Risk factors and specific modifiers of the dose-response relationship may vary among different populations and not be well recognized. Many thyroid studies have considered thyroid nodularity itself, but not specific morphological types of thyroid nodules. There are many specific types of thyroid nodules which follow a morphological classification of thyroid lesions, including some congenital and tumor-like conditions. Modern equipment and technique can help us to identify particular specific types of thyroid nodules. In this study we report some results of a clinically applicable approach to materials derived from three studies. From 1999 through 2002, we have screened 571 current residents from 4 exposed and 1 control village near the Semipalatinsk Nuclear Test Site area, who were of similar ages (<20) at the time of major radiation fallout events at the SNTS. Prevalent nodules were identified by ultrasound and fine-needle aspiration biopsy, cytopathology results. Analysis of ultrasound images and cytopathology of thyroid lesions among exposed and non-exposed population allowed us to distinguish some interesting ultrasound features for specific types of thyroid nodules. We believe that it would be interesting and possibly more informative for thyroid dosimetry studies to consider specific morphological types of thyroid nodules. We need more detailed research to clarify the feasibility of applying these findings for study of the dose-response relationship.

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

A novel hNIS/tdTomato fusion reporter for visualizing the relationship between the cellular localization of sodium iodide symporter and its iodine uptake function under heat shock treatment.

PubMed

Yeom, Chan Joo; Chung, Taemoon; Youn, Hyewon; Kang, Keon Wook; Lee, Dong Soo; Chung, June-Key

2015-01-01

The function of membrane-localized sodium iodide symporter (NIS) determines the efficacy of radioiodine therapy in thyroid cancer. Here, we describe a dual mode reporter fused with human NIS (hNIS) and a red fluorescent protein named tandem dimeric Tomato (tdTomato) for the in vitro and in vivo imaging of hNIS protein expression, localization, and iodide uptake function. Human cervical epithelial adenocarcinoma cell line (HeLa)-hNIS/tdTomato cells were established by transducing a fusion gene expressing hNIS/tdTomato under the control of a cytomegalovirus promoter. Fluorescence imaging, confocal microscopy, and an 125I uptake assay were performed to validate the integrity of the fusion protein. Actinomycin D and cycloheximide were used to block newly synthesized hNIS proteins. In vivo images were acquired using a gamma camera and a Maestro fluorescence imaging device. The fluorescence intensity of membrane-localized hNIS and 125I uptake both were increased after heat shock. Scintigraphy and fluorescence imaging indicated specific accumulation of the hNIS/tdTomato fusion protein in xenografted tumors, supporting the utility of this system for in vivo monitoring of hNIS expression and activity. We developed a novel hNIS/tdTomato dual mode reporter that enables visualization of the expression, localization, and iodine uptake function of hNIS in vitro and in vivo.

Thyroiditis: a Clinico-cytomorphological Study with a Reference to the Ethnic Groups of Northeast Regions of India.

PubMed

Kalita, Abhijit; Baruah, Ronica

2015-12-01

Definite clinico-cytological criterion is outlined for thyroid lesions. Fine needle aspiration cytology (FNAC) makes it easier to segregate cases of thyroiditis (Chronic lymphocytic thyroiditis/Hashimoto's thyroiditis-CLT/HT, and subacute thyroiditis-SAT) from other benign and malignant lesions of thyroid. The study was done for a period of 5½ years at a diagnostic centre in Guwahati. Patients underwent FNAC and smears were studied for cytomorphology. A correlation with clinical features and thyroid function, including antithyroid antibody estimation, was done, wherever possible. 792 thyroid lesions were encountered during the study, of which 213 (26.89 %) were cases of thyroiditis (70.43 % CLT/HT, 24.9 % SAT and 3.76 % having overlapping features of CLT/HT and SAT); 2 cases (0.9 %) of CLT showed suspicion of Non-Hodgkin's Lymphoma (NHL), which was confirmed on histopathology. 24 cases (11.26 %) belonged to different ethnic tribal groups of Northeast India. CLT/HT presented predominantly with diffuse thyroid enlargement, but 12 cases (8 % of CLT/HT cases) had nodular enlargement. Patients presented with predominantly hypothyroidism; however occasional hyperthyroid cases were also seen. SAT showed signs of inflammation and presented with hyperthyroidism. Overlap cases of CLT/HT and SAT showed combined clinico-cytomorphological features of both lesions. 37.5 % cases with overlapping features belonged to tribal communities. A rise in incidence of thyroiditis, particularly CLT/HT, was seen. Overlap features of CLT/HT and SAT was noticed in significant percentage. No bias was noticed amongst any specific tribal community. FNAC, coupled with clinico-serological study, helps to diagnose thyroiditis at early stage.

Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.

PubMed

Meng, Li; Rijntjes, Eddy; Swarts, Hans J M; Keijer, Jaap; Teerds, Katja J

2017-03-16

There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular reserve and the size of the growing follicle population, which may impact fertility.

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasselgren, P.O.; Chen, I.W.; James, J.H.

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of /sup 14/C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Txmore » rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.« less

Interaction between perchlorate and iodine in the metamorphosis of Hyla versicolor

USGS Publications Warehouse

Sparling, D.; Harvey, G.; Nzengung, V.; ,

2003-01-01

Perchlorate (ClO4-) is a water-soluble, inorganic anion that is often combined with ammonium, potassium or other cations for use in industry and agriculture. Ammonium perchlorate, for example, is a potent oxidizer and is used in various military applications including rocket fuel. It has also been found in an historically widely used fertilizer, Chilean nitrate and in other fertilizers. It has been found in ground and surface waters of over 30 states and is considered a human health risk. Because of its similar atomic radius and volume, perchlorate competes with iodide for thyroid uptake and storage and thereby inhibits production of thyroid hormones. Amphibians may be particularly affected by perchlorate because they rely on the thyroid for metamorphosis. This study exposed early larval Hyla versicolor to concentrations of perchlorate ranging from 2.2 to 50 ppm to determine the effects of perchlorate on a native amphibian. In addition, three controls, 0 perchlorate, 0 perchlorate with 0.10 ppm iodide (C + I) and 50 ppm perchlorate + 0.10 ppm iodide (50 + I) were tested. Mortality (< 11% with all treatments) and growth appeared to be unaffected by perchlorate. Inhibition of development started with 2.2 ppm perchlorate and little or no development occurred at 22.9 ppm and above. This inhibition was particularly apparent at the latter stages of development including hindlimb formation and metamorphosis. The estimated EC50 for total inhibition of metamorphosis at 70 days of treatment was 3.63 ppm. There was no evidence of inhibition of development with the 50 + I, C + I, or controls, indicating that the presence of small concentrations of iodide could counter the effects of perchlorate. When tadpoles that had been inhibited by perchlorate were subsequently treated with iodide, development through prometamorphosis progressed but mortality was very high.

Interaction between perchlorate and iodine in the metamorphosis of Hyla versicolor

USGS Publications Warehouse

Sparling, D.W.; Harvey, G.; Nzengung, V.; Linder, Gregory L.; Krest, Sherry K.; Sparling, Donald W.; Little, Edward E.

2003-01-01

Perchlorate (ClO4-) is a water-soluble, inorganic anion that is often combined with ammonium, potassium or other cations for use in industry and agriculture. Ammonium perchlorate, for example, is a potent oxidizer and is used in various military applications including rocket fuel. It has also been found in an historically widely used fertilizer, Chilean nitrate and in other fertilizers. It has been found in ground and surface waters of over 30 states and is considered a human health risk. Because of its similar atomic radius and volume, perchlorate competes with iodide for thyroid uptake and storage and thereby inhibits production of thyroid hormones. Amphibians may be particularly affected by perchlorate because they rely on the thyroid for metamorphosis. This study exposed early larval Hyla versicolor to concentrations of perchlorate ranging from 2.2 to 50 ppm to determine the effects of perchlorate on a native amphibian. In addition, three controls, 0 perchlorate, 0 perchlorate with 0.10 ppm iodide (C + I) and 50 ppm perchlorate + 0.10 ppm iodide (50 + I) were tested. Mortality (<11% with all treatments) and growth appeared to be unaffected by perchlorate. Inhibition of development started with 2.2 ppm perchlorate and little or no development occurred at 22.9 ppm and above. This inhibition was particularly apparent at the latter stages of development including hindlimb formation and metamorphosis. The estimated EC50 for total inhibition of metamorphosis at 70 days of treatment was 3.63 ppm. There was no evidence of inhibition of development with the 50 + I, C + I, or controls, indicating that the presence of small concentrations of iodide could counter the effects of perchlorate. When tadpoles that had been inhibited by perchlorate were subsequently treated with iodide, development through prometamorphosis progressed but mortality was very high.

Influence of the autonomic nervous system on calcium homeostasis in the rat.

PubMed

Stern, J E; Cardinali, D P

1994-01-01

The local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.

Norepinephrine and thyroxine are predictors of fat mass gain in humans with cold-induced brown adipose tissue activation.

PubMed

Begaye, Brittany; Piaggi, Paolo; Thearle, Marie S; Haskie, Kaitlyn; Walter, Mary; Schlögl, Mathias; Bonfiglio, Susan; Krakoff, Jonathan; Vinales, Karyne L

2018-05-16

In healthy adults with detectable cold-induced brown fat activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Twelve healthy volunteers (7M/5F) with positive CIBA (>2 standardized uptake value (g/mL)) had 24-h energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron-emission tomography/computed tomography scans were performed after exposure to 16°C for 2h to quantify CIBA. CIBA, 24hEE during EBL and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 (fT3) and free t4 (fT4). Body composition at baseline and six months by DXA. Lower urinary norepinephrine and fT4 were associated with higher CIBA (r = ‒0.65, p = 0.03 and r = ‒0.75, p<0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (p=0.77). Lower CIBA (β = ̶̶ 3.5 kg/SUV, p<0.01) predicted fat mass gain; whereas, higher urinary norepinephrine and fT4 predicted future fat mass gain at 6 months (β = 3.0 kg per two-fold difference in norepinephrine, p=0.03; β = 1.2 kg per 0.1 ng/dL difference in fT4, p=0.03, respectively). Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

[(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.

PubMed

Iten, Fabienne; Muller, Beat; Schindler, Christian; Rasch, Helmut; Rochlitz, Christoph; Oertli, Daniel; Maecke, Helmut R; Muller-Brand, Jan; Walter, Martin A

2009-05-15

The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [(90)Y-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [(90)Y-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). Response to [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

PubMed

Taïeb, D; Sebag, F; Cherenko, M; Baumstarck-Barrau, K; Fortanier, C; Farman-Ara, B; De Micco, C; Vaillant, J; Thomas, S; Conte-Devolx, B; Loundou, A; Auquier, P; Henry, J F; Mundler, O

2009-07-01

Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma.

PubMed

Wong, K K; Zarzhevsky, N; Cahill, J M; Frey, K A; Avram, A M

2009-10-01

Hybrid imaging modalities such as radioiodine single photon emission CT with integrated CT ((131)I SPECT-CT) and 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography with integrated CT (FDG PET-CT) allow the rapid and efficient fusion of functional and anatomic images, and provide diagnostic information that may influence management decisions in patients with differentiated thyroid carcinoma (DTC). Diagnostic localisation and therapy of these tumours are dependent upon their capacity to concentrate radioiodine ((131)I) via uptake through the sodium-iodide symporter and retention within the tumour. The prognosis for most patients with DTC is favourable, although controversy exists regarding the role of post-operative (131)I therapy in patients at low-risk for disease. Accurate identification of functional thyroid tissue (benign or malignant) using diagnostic (131)I planar scintigraphy complemented by SPECT-CT imaging enables the completion of post-operative staging and patient risk stratification prior to (131)I therapy administration. In patients with non-iodine-avid tumours (negative (131)I scan but elevated thyroglobulin indicative of persistent or recurrent disease), FDG PET-CT is used to identify tumours with enhanced glucose metabolism and to localise the source of thyroglobulin production. The CT component of this hybrid technology provides anatomic localisation of activity and allows CT-based attenuation correction of PET images. Images from 15 patients illustrate the applications of (131)I SPECT-CT and FDG PET-CT.

The widened use of exogenous stimulation with recombinant human TSH to treat metastatic thyroid carcinoma in Italy.

PubMed

Maffioli, L; Florimonte, L; Fugazzola, L; Banti, E; Bagnasco, M; Dottorini, M E; Perotti, G; Rubello, D; Seregni, E; Bombardieri, E; Testori, O

2012-10-01

Recently, in Italy, the reimbursement for the use of rhTSH in preparing patients for radiometabolic treatment of iodine-avid metastases from differentiated thyroid cancer has been made possible. Intramuscular administration of rhTSH increases the radioiodine uptake and thyroglobulin production by thyroid cells. In addition to the previous indications on the use of rhTSH (mainly: serum thyreoglobulin assay with or without 131I scintigraphy and ablation with 131I of remnants in low risk patients), the reimbursement is now allowed for the treatment with radioiodine of iodine-avid loco-regional and distant metastases, in subjects with inability to reach adequate TSH levels and/or severe clinical conditions which could be potentially worsened by other concurrent diseases (history of stroke or transient ischemic attack, severe cardiac disease, renal failure or major psychiatric disorders). The Italian Medicines Agency (AIFA) approved this use (and added this hormone in the special list of drugs regulated by the D.Lgs 648/96) on the basis of a series of scientific evidences, proposed by a "team of experts". In the present paper we illustrate the scientific background of the use of rhTSH (clinical usefulness, economic considerations, aspects related to a better quality of life) that allowed the modification of the reimbursement and how it was made possible in the Italian legislative context.

Thyroid autoimmunity and function among Ugandan children and adolescents with type-1 diabetes mellitus.

PubMed

Muhame, Rugambwa Michael; Mworozi, Edison Arwanire; McAssey, Karen; Lubega, Irene

2014-01-01

Up to 30% of type-1 diabetes mellitus (T1DM) patients have co-existent thyroid autoimmunity with up to 50% of them having associated thyroid dysfunction. Routine screening for thyroid autoimmunity and dysfunction is recommended in all T1DM patients. However, this was not currently practiced in Ugandan paediatric diabetes clinics. There was also paucity of data regarding thyroid autoimmunity and dysfunction in African children and adolescents with diabetes mellitus. The objective of this study was to quantify the magnitude of thyroid autoimmunity and dysfunction in Ugandan children with TIDM. This was a cross sectional descriptive study to determine the prevalence of thyroid autoantibodies and describe thyroid function among children and adolescents aged 1-19 years with diabetes mellitus attending the paediatric diabetes clinic at Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we obtained details of clinical history and performed physical examination. Blood (plasma) was assayed to determine levels of antibodies to thyroid peroxidase (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). The prevalence of thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO positive subjects. All study subjects were clinically euthyroid; however, 7.3% (5/69) of the study subjects had subclinical hypothyroidism. These data strengthen the argument for routine screening of all diabetic children and adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by international guidelines. We also recommend evaluation of thyroid function in diabetic children and adolescents to minimize the risk of undiagnosed thyroid dysfunction.

Thyroid Function and Obesity

PubMed Central

Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

2012-01-01

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail. PMID:24783015

Evaluation of autoimmune thyroid disease in melasma.

PubMed

Rostami Mogaddam, Majid; Iranparvar Alamdari, Manouchehr; Maleki, Nasrollah; Safavi Ardabili, Nastaran; Abedkouhi, Selma

2015-06-01

Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun-exposed areas. To date, few studies have been conducted about the relationship between thyroid autoimmun-ity and melasma. To evaluate the thyroid dysfunction and autoimmunity in nonpregnant women with melasma. A total of 70 women with melasma and 70 age-matched healthy women with no history of melasma were enrolled in the study. We studied the thyroid hormone profile in both groups. The statistical analysis was performed using SPSS software. Patients with melasma had 18.5% frequency of thyroid disorders, and 15.7% had positive anti-TPO, while subjects from the control group had a 4.3% frequency of thyroid abnormalities, and only 5.7% had positive anti-TPO. There was a significantly higher prevalence of thyroid dysfunction in women with melasma compared with control group (P = 0.008). This study suggests that there is a relationship between thyroid autoimmunity and melasma. However, to make recommendations on screening for thyroid disease in patients with melasma, future research of good methodological quality is needed. © 2015 Wiley Periodicals, Inc.

Predictive factors of thyroid cancer in patients with Graves' disease.

PubMed

Ren, Meng; Wu, Mu Chao; Shang, Chang Zhen; Wang, Xiao Yi; Zhang, Jing Lu; Cheng, Hua; Xu, Ming Tong; Yan, Li

2014-01-01

The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Development of a Reference Dose for Perchlorate: Current Issues and Status

NASA Technical Reports Server (NTRS)

Pleus, R. C.; Goodman, G.; Mattie, D. R.

2000-01-01

The perchlorate anion (ClO4) is typically manufactured as the ammonium salt. The most common use of ammonium perchlorate is in the aerospace program as a component of solid rocket fuel. The perchlorate anion is exceedingly stable under environmental conditions and has been found in ground and surface waters in CA, NV, UT, AZ, TX, AK, NY, MD, WV and FL. The National Center for Environmental Assessment (NCEA) of the U.S. Environmental Protection Agency (US EPA) is in the process of developing an oral reference dose (RfD) for perchlorate. An oral RfD is a body-weight-adjusted dose that can be consumed daily over an entire lifetime with the expectation of no adverse health effects. Once developed, the new RfD will be used by US EPA as the basis of a safe-drinking-water level (SDWL) guideline. US EPA and regional regulatory agencies will then jointly or separately propose clean-up action levels for ground and surface waters at contaminated sites. The toxicological database on CIO4- as of March 1997 was determined by an expert peer-review panel to be inadequate for the purpose of deriving an oral RfD. For example, little or no experimental data existed on the subchronic, reproductive, or developmental toxicity of perchlorate. To fill gaps in the toxicological database, eight animal studies were designed by a government-industry consortium that included US EPA and AFRL. These studies were performed in 1997-1998. It has been known for many years that in the thyroid, high doses of perchlorate block the function of iodide by competing for iodide binding sites. Perchlorate was used in the 1950s-60s as a treatment for Graves' disease (a hyperthyroid condition). Because of what was already known about the pharmacological mode of action of perchlorate, specific concerns addressed in the design of the recent animal studies included the potential for developmental toxicity, notably neurological development. Upon review of complete study reports from four of the studies and incomplete data from the other two, US EPA/NCEA issued a document in December 1998 stating that the critical effects were hormone and histology data from the neurodevelopmental/behavioral toxicity study that had been performed in rats; an RfD was proposed based upon the observation of thyroid-follicular-cell hypertrophy in the 5-day-old pups (PND) of dams given perchlorate in drinking water at 0.1 mg/kg-day (the lowest dose tested) in this study. US EPA/NCEA also focused attention on a nonsignificant increase in motor activity observed in 14-day-old male pups in the same study at the same dose. In February 1999, a public workshop was convened at which an external peer-review panel determined that there was still insufficient data to support the development of a RfD. Additional studies were recommended. Since that time a clinical study revealed significant depression of thyroidal uptake of iodide in volunteers receiving potassium perchlorate at 10 mg/day for 14 days. Follow-up studies currently underway include a pathology working-group review of histology slides from the all of the previous studies, a motor activity study similar to the first behavioral study, an additional immunotoxicity study, male and female rat kinetic studies, a hormone interlaboratory study, and an effects study for thyroid and brain in developing rats. These studies are expected to be complete by mid-2000. A clinical study is planned to determine inhibition of iodide uptake and kinetic parameters in humans following 14-day perchlorate ingestion. The kinetics studies will provide data for developing physiologically based pharmacokinetic (PBPK) models for rats and humans needed to establish the RfD.

Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

PubMed

Raikov, Nikolai; Nonchev, Boyan; Chaushev, Borislav; Vjagova, Diyana; Todorov, Svetoslav; Bocheva, Yana; Malceva, Daniela; Vicheva, Snejinka; Raikova, Asyia; Argatska, Antoaneta; Raikov, Miroslav

2016-01-01

The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

Basis of the Massachusetts reference dose and drinking water standard for perchlorate.

PubMed

Zewdie, Tsedash; Smith, C Mark; Hutcheson, Michael; West, Carol Rowan

2010-01-01

Perchlorate inhibits the uptake of iodide in the thyroid. Iodide is required to synthesize hormones critical to fetal and neonatal development. Many water supplies and foods are contaminated with perchlorate. Exposure standards are needed but controversial. Here we summarize the basis of the Massachusetts (MA) perchlorate reference dose (RfD) and drinking water standard (DWS), which are considerably lower and more health protective than related values derived by several other agencies. We also review information regarding perchlorate risk assessment and policy. MA Department of Environmental Protection (DEP) scientists, with input from a science advisory committee, assessed a wide range of perchlorate risk and exposure information. Health outcomes associated with iodine insufficiency were considered, as were data on perchlorate in drinking water disinfectants. We used a weight-of-the-evidence approach to evaluate perchlorate risks, paying particular attention to sensitive life stages. A health protective RfD (0.07 microg/kg/day) was derived using an uncertainty factor approach with perchlorate-induced iodide uptake inhibition as the point of departure. The MA DWS (2 microg/L) was based on risk management decisions weighing information on perchlorate health risks and its presence in certain disinfectant solutions used to treat drinking water for pathogens. Current data indicate that perchlorate exposures attributable to drinking water in individuals at sensitive life stages should be minimized and support the MA DEP perchlorate RfD and DWS. Widespread exposure to perchlorate and other thyroid toxicants in drinking water and foods suggests that more comprehensive policies to reduce overall exposures and enhance iodine nutrition are needed.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

The Effect of Electromagnetic Radiation due to Mobile Phone Use on Thyroid Function in Medical Students Studying in a Medical College in South India.

PubMed

Baby, Nikita Mary; Koshy, George; Mathew, Anna

2017-01-01

Enormous increase in mobile phone use throughout the world raises widespread concerns about its possible detrimental effect on human health. Radiofrequency waves are emitted by cell phones. They are non-ionising and the effect on the thyroid gland is part of their non thermal effects. The thyroid gland may be particularly vulnerable to this effect because of its normal anatomical position. The study was done to explore the association between radiation exposure and thyroid dysfunction among mobile phone users. It had an exploratory design and unit survey method to collect information from all medical students in a medical college in South India. Inclusion criteria included active use of mobile phone prior to and during the study period. Criteria for exclusion was presence of pre-existsting thyroid disease,thyroid nodule,thyroid goitre/nodule and altered thyroid function. The sample size was 83 undergraduate students. 71% of respondents had no family history of thyroid illness. Among the remainder,20.5% had a first degree relative with thyroid dysfunction,8.4% had a second degree relative affected. Clinical examination revealed that 79.5% of the respondents were normal,13.6% had thyroid swelling,3.6% had symptoms of thyroid dysfunction and 3.6% had both thyroid swelling and symptoms of thyroid dysfunction. 53% of the respondents spent 0.5 hrs on an average talking on the phone daily,28.9% spent 1.5 hrs daily and 10.8% of respondents spent over 3.5 hours. We found there was a significant correlation between total radiation exposure and an increase in TSH among both groups -in those with and without family history of thyroid illness. In our study there was a significant correlation between total radiation exposure and increasing TSH values among both all respondents.

Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

PubMed

Goodman, Julie E; Kerper, Laura E; Boyce, Catherine Petito; Prueitt, Robyn L; Rhomberg, Lorenz R

2010-10-01

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

PubMed

Hurley, P M

1998-08-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

The relationship between procalcitonin and thyroid autoantibodies in patients with autoimmune thyroiditis.

PubMed

Oncul, Ali; Ates, Ihsan; Arikan, Mehmet Fettah; Yilmaz, Nisbet; Topcuoglu, Canan; Yilmaz, Fatma Meric; Altay, Mustafa

2017-11-01

The aim of this study is to investigate the serum levels of procalcitonin and its association with autoantibodies in patients with euthyroid Hashimoto's thyroiditis. A total of 80 participants were included in the study; 40 of which were newly diagnosed with Hashimoto's thyroiditis, aged over 18, and 40 of which were healthy volunteers. The serum levels of procalcitonin were measured by enzyme-linked immunosorbent assay kit. Thyroid function tests were analyzed in hormone laboratory with Electro-chemiluminescence immunoassay. Hashimoto's thyroiditis patients had higher median procalcitonin levels than those of the control group (34.3 pg/mL vs 27.8 pg/mL respectively; P=.037). Also, male patients had higher median procalcitonin levels as compared to female patients (37 pg/mL vs 27 pg/mL respectively; P=.013). In the Hashimoto's thyroiditis group, procalcitonin level was positively correlated with anti-thyroglobulin and anti-thyroid peroxidase levels (r=.559, P<.001; r=634, P<.001, respectively). The procalcitonin and anti-thyroid peroxidase levels were identified to be an independent predictor in diagnosis of Hashimoto's thyroiditis. The fact that procalcitonin was found to be correlated with thyroid autoantibodies and found to be an independent risk factor for Hashimoto's thyroiditis in the regression analysis in the framework of this study urges us to think that procalcitonin may be associated with the autoimmunity. © 2017 Wiley Periodicals, Inc.

Hypothyroxinemia induced by mild iodine deficiency deregulats thyroid proteins during gestation and lactation in dams.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-08-02

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I- symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.

Need of tetraiodothyronine supplemental therapy in pregnant women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid hormones are essential for fetal development. Normal thyroid function in pregnant women adjusts by itself in cases of pregnancy, phenomenon that is deficient in cases of previous maternal thyroid disease. The study group was represented by 120 females, with reproductive age, with known thyroid disease, that had a up to delivery pregnancy. Thyroid ultrasound parameters and functional parameters were follow-up during the 9-month of gestation. The study proposes a mathematical model of predicting the need and the amount of tetraiodothyronine treatment in pregnant women with prevalent thyroid disease.

Thyroid Volume and Its Relation to Anthropometric Measures in a Healthy Cuban Population

PubMed Central

Turcios, Silvia; Lence-Anta, Juan J.; Santana, Jose-Luis; Pereda, Celia M.; Velasco, Milagros; Chappe, Mae; Infante, Idalmis; Bustillo, Marlene; García, Anabel; Clero, Enora; Maillard, Stephane; Rodriguez, Regla; Xhaard, Constance; Ren, Yan; Rubino, Carole; Ortiz, Rosa M.; de Vathaire, Florent

2015-01-01

Objectives The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. Study Design Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. Results The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. Conclusion Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit. PMID:25960963

Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance.

PubMed

Iype, Elizabeth Mathew; Jagad, Vijay; Nochikattil, Santhosh Kumar; Varghese, Bipin T; Sebastian, Paul

2016-02-01

Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement.

What Do Korean Women Know and Want to Know about Thyroid Cancer? A Qualitative Study.

PubMed

Lee, Bomyee; Park, Jae Young; Shin, Hye Young; Park, Sang Hee; Choi, Eun-Bi; Yoo, Jisu; Choi, Kui Son; Jun, Jae Kwan

2016-01-01

Despite increasing debate about overdiagnosis and overtreatment of thyroid cancer in Korea, information to guide decisions on whether or not to undergo screening for and treatment of abnormal lesions of the thyroid is lacking. Moreover, studies have yet to outline what lay people know and want to know about thyroid cancer. The primary aim of this study was to explore general awareness of thyroid cancer among Korean women, their sources of information, and their satisfaction with the information they are provided. The secondary aim was to investigate information needs about thyroid cancer. A qualitative study using focus group interviews was conducted. Twenty-nine women were divided into four groups: (1) participants who had never undergone thyroid ultrasound screening; (2) those who had undergone screening, (3) those who continued to undergo regular check-ups with ultrasonography for benign nodules of the thyroid; and (4) participants who had undergone surgery for thyroid cancer. A widespread lack of awareness of information on thyroid cancer was noted among participants in groups 1 and 2 who were not well aware of thyroid cancer and generally recognized it as a'good cancer'. Surprisingly, instead of doctors and medical personnel, most participants reported obtaining information from acquaintances and media outlets. Moreover, most participants described dissatisfaction with their experience with screening and a lack of explanation on treatment and test results from medical personnel. Women in Korea seek reliable information on thyroid cancer that could help them to better understand the disease and make informed decisions regarding screening and treatment. More effort is needed from medical personnel to communicate the implications of thyroid cancer, screening results, and treatments thereof to lay people.

Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

PubMed

Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

2012-11-01

To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.

Thyroid Autoimmunity in Girls with Turner Syndrome.

PubMed

Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata

2017-01-01

Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.

PubMed

Gupta, Monica; Singhal, Lalita; Kumar, Akshay

2018-06-01

Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

PubMed

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

Alcohol Intake and Risk of Thyroid Cancer: A Meta-Analysis of Observational Studies.

PubMed

Hong, Seung-Hee; Myung, Seung-Kwon; Kim, Hyeon Suk

2017-04-01

The purpose of this study was to assess whether alcohol intake is associated with the risk of thyroid cancer by a meta-analysis of observational studies. We searched PubMed and EMBASE in June of 2015 to locate eligible studies. We included observational studies such as cross-sectional studies, case-control studies, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) with 95% confidence intervals (CIs). We included 33 observational studies with two cross-sectional studies, 20 case-controls studies, and 11 cohort studies, which involved a total of 7,725 thyroid cancer patients and 3,113,679 participants without thyroid cancer in the final analysis. In the fixed-effect model meta-analysis of all 33 studies, we found that alcohol intake was consistently associated with a decreased risk of thyroid cancer (OR or RR, 0.74; 95% CI, 0.67 to 0.83; I 2 =38.6%). In the subgroup meta-analysis by type of study, alcohol intake also decreased the risk of thyroid cancer in both case-control studies (OR, 0.77; 95% CI, 0.65 to 0.92; I 2 =29.5%; n=20) and cohort studies (RR, 0.70; 95% CI, 0.60 to 0.82; I 2 =0%; n=11). Moreover, subgroup meta-analyses by type of thyroid cancer, gender, amount of alcohol consumed, and methodological quality of study showed that alcohol intake was significantly associated with a decreased risk of thyroid cancer. The current meta-analysis of observational studies found that, unlike most of other types of cancer, alcohol intake decreased the risk of thyroid cancer.

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

PubMed

Kroiss, A; Putzer, D; Decristoforo, C; Uprimny, C; Warwitz, B; Nilica, B; Gabriel, M; Kendler, D; Waitz, D; Widmann, G; Virgolini, I J

2013-04-01

We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). (68)Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

A perchlorate sensitive iodide transporter in frogs

PubMed Central

Carr, Deborah L.; Carr, James A.; Willis, Ray E.; Pressley, Thomas A.

2008-01-01

Nucleotide sequence comparisons have identified a gene product in the genome database of African clawed frogs (Xenopus laevis) as a probable member of the solute carrier family of membrane transporters. To confirm its identity as a putative iodide transporter, we examined the function of this sequence after heterologous expression in mammalian cells. A green monkey kidney cell line transfected with the Xenopus nucleotide sequence had significantly greater 125I uptake than sham-transfected control cells. The uptake in carrier-transfected cells was significantly inhibited in the presence of perchlorate, a competitive inhibitor of mammalian Na+/iodide symporter. Tissue distributions of the sequence were also consistent with a role in iodide uptake. The mRNA encoding the carrier was found to be expressed in the thyroid gland, stomach, and kidney of tadpoles from X. laevis, as well as the bullfrog Rana catesbeiana. The ovaries of adult X. laevis also were found to express the carrier. Phylogenetic analysis suggested that the putative X. laevis iodide transporter is orthologous to vertebrate Na+-dependent iodide symporters. We conclude that the amphibian sequence encodes a protein that is indeed a functional Na+/iodide symporter in Xenopus laevis, as well as Rana catesbeiana. PMID:18275962

Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving fertility.

PubMed

Medenica, S; Nedeljkovic, O; Radojevic, N; Stojkovic, M; Trbojevic, B; Pajovic, B

2015-01-01

Thyroid disease is the second most common endocrine condition in women of childbearing age. Thyroid hormones are involved in control of menstrual cycle and in achieving fertility affecting the actions of follicle-stimulating hormone and luteinizing hormone on steroid biosynthesis by specific triiodothyronine sites on oocytes; therefore, affect all aspects of reproduction. It remains controversial if pregnant women should be screened for thyroid dysfunction. Purpose of this review was to examine recent studies on the assessment of thyroid dysfunction in pregnancy, its treatment and newly perspective of thyroid autoimmunity in pregnant euthyroid women in achieving fertility. An electronic search was conducted using the internet medical databases: Medline/PubMed, EMBASE, EBSCO, and the Cochrane library. Thyroid gland faces great challenge in pregnancy when many hormonal changes occur. Precondition for normal follicular development and ovulation is pulsate gonadothropin realizing hormone secretion. Thyroid dysfunction in pregnancy is classified as forms of hypothyroidism (positivity of thyroid autoantibody, isolated hypothyroidism, and subclinical or overt hypothyroidism), hyperthyroidism, and autoimmune disease, but also thyroid nodules and cancer, iodine insufficiency and postpartum thyroiditis. These conditions can cause adverse effects on mother and fetus including pregnancy loss, gestational hypertension, or pre-eclampsia, pre-term delivery, low birth weight, placental abruption and postpartum hemorrhage. There is an evidence that thyroid autoimmunity, in thyroid dysfunction adversely affects conception and pregnancy outcomes, but it is unclear what impact has isolated eumetabolic thyroid autoimmunity in achieving fertility, especially in women undergoing in vitro fertilization. Treatment of euthyroid pregnant women with positive thyroid peroxides antibodies is still controverse, but not few studies show that levothyroxine substitution is able to lower the chance of miscarriage and premature delivery. Further randomized trials are needed to expand our knowledge of physiologic changes in thyroid function during the pregnancy and to reveal mechanisms by which thyroid autoimmunity in euthyroid women affect fertility, especially the success of assisted reproductive technology in achieving the same and validity of levothyroxine administration in thyroid autoimmunity positive women.

Thyroid disease in pustulosis palmoplantaris.

PubMed

Agner, T; Sindrup, J H; Høier-Madsen, M; Hegedüs, L

1989-10-01

An increased frequency of thyroid autoantibodies has been reported in patients with palmar and plantar pustulosis (PPP). This study was undertaken to determine the frequency and type of thyroid disease in 32 patients with this disease compared with a control group. Thyroid disease was demonstrated in 53% of the patients with PPP as compared to 16% in the matched control group. Fourteen patients with PPP had an enlarged thyroid and in six there were thyroid autoantibodies. There appears to be an increased incidence of goitre and thyroid autoantibodies in PPP with a decrease in the level of the thyroid hormones.

Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the hanford nuclear site.

PubMed

Davis, Scott; Kopecky, Kenneth J; Hamilton, Thomas E; Onstad, Lynn

2004-12-01

Approximately 740,000 Ci (2.73 x 10(16) Bq) of iodine 131 (131I) were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. The risk of thyroid disease resulting from prolonged environmental 131I exposure is poorly understood. The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of 131I from Hanford. Retrospective cohort study. Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's 131I releases were estimated from interview data regarding residence and dietary histories. The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. Of 5199 individuals identified, 4350 were located alive and 3440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. Thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. These results do not support the hypothesis that exposure during infancy and childhood to 131I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study.

Current practice of radioiodine treatment in the management of differentiated thyroid cancer in Germany.

PubMed

Hoelzer, S; Steiner, D; Bauer, R; Reiners, C; Farahati, J; Hundahl, S A; Dudeck, J

2000-10-01

This prospective, observational study of a cohort of thyroid cancer patients in Germany focusses on the "real-world" practice in the management of thyroid cancer patients. This report includes data from 2376 patients with primary differentiated thyroid carcinoma first diagnosed in the year 1996. The study reveals considerable differences in actual practice concerning surgery and radioiodine treatment. The results indicate that consensus is lacking with respect to the multimodality treatment approach for differentiated thyroid carcinoma. Our analysis represents the most current and comprehensive national assessment of presenting patient characteristics, diagnostic tests, treatment and complications for thyroid cancer.

Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer.

PubMed

Son, Haiyoung; Lee, Sang Mi; Yoon, Ra Gyoung; Lee, Hakmin; Lee, Ilkyun; Kim, Soon; Chung, Woong Youn; Lee, Jeong Won

2017-01-01

In the current study, we examined whether selenium supplementation during iodine-131 ( 131 I) treatment had a radio-protective effect on salivary glands. Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131 I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131 I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131 I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131 I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated. Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131 I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05). Selenium supplementation during 131 I treatment was effective to reduce salivary glands damage by 131 I radiation in patients with differentiated thyroid cancer.

Hypocalcaemia after thyroid surgery for differentiated thyroid carcinoma: preliminary study report.

PubMed

Radivojević, Renata Curić; Prgomet, Drago; Markesić, Josip; Ezgeta, Carmen

2012-11-01

Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first choice treatment for differentiated thyroid carcinoma (DTC). The study comprised 46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.

Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

PubMed Central

Zhao, Pengxin; Zhang, Kaili

2016-01-01

Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. PMID:27446209

Effect of specific activity on organ uptake of iodine-123-meta-iodobenzylguanidine in humans.

PubMed

Farahati, J; Lassmann, M; Scheubeck, M; Bier, D; Hanscheid, H; Schelper, L; Grelle, I; Biko, J; Werner, E; Graefe, K; Reiners, C

1997-04-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activity on organ uptake of radioiodinated MIBG. the kinetics of no-carrier-added (n.c.a.) [I-123]MIBG (greater than or equal to 7.4 TBq/mu mol) were compared with those of commercial (com.) [I-123]MIBG (similar to 74 MBq/mu mol) in 3 healthy volunteers by serial imaging and blood sampling. The organ uptake of radioiodinated MIBG did not remarkably differ between the two specific activities. Due to rapid degradation a more pronounced accumulation of radioactivity was present in plasma alter n.c.a. than after com. [I-123]MIBG resulting in a higher background and thyroid activity. In addition due to a prolonged residence time of the radioactivity, the radiation exposure to organs was in general slightly higher with n.c.a. [I-123]MIBG as compared to com. [I-123]MIBG. This finding highlights the higher in vivo deiodination of n.c.a. [I-123]MIBG than of com. [I-123]MIBG in humans. In the treatment of children suffering from neuroblastoma, therefore, degradation of n.c.a. [I-123]MIBG may decrease the concentration of radioiodinated MIBG available for binding at tumor sites and result in higher radiation exposure of non-tumor tissue.

Thyroid hormone effects on mitochondrial energetics.

PubMed

Harper, Mary-Ellen; Seifert, Erin L

2008-02-01

Thyroid hormones are the major endocrine regulators of metabolic rate, and their hypermetabolic effects are widely recognized. The cellular mechanisms underlying these metabolic effects have been the subject of much research. Thyroid hormone status has a profound impact on mitochondria, the organelles responsible for the majority of cellular adenosine triphosphate (ATP) production. However, mechanisms are not well understood. We review the effects of thyroid hormones on mitochondrial energetics and principally oxidative phosphorylation. Genomic and nongenomic mechanisms have been studied. Through the former, thyroid hormones stimulate mitochondriogenesis and thereby augment cellular oxidative capacity. Thyroid hormones induce substantial modifications in mitochondrial inner membrane protein and lipid compositions. Results are consistent with the idea that thyroid hormones activate the uncoupling of oxidative phosphorylation through various mechanisms involving inner membrane proteins and lipids. Increased uncoupling appears to be responsible for some of the hypermetabolic effects of thyroid hormones. ATP synthesis and turnover reactions are also affected. There appear to be complex relationships between mitochondrial proton leak mechanisms, reactive oxygen species production, and thyroid status. As the majority of studies have focused on the effects of thyroid status on rat liver preparations, there is still a need to address fundamental questions regarding thyroid hormone effects in other tissues and species.