Regulation of vernal migration in Gambel's white-crowned sparrows: Role of thyroxine and triiodothyronine.

PubMed

Pérez, Jonathan H; Furlow, J David; Wingfield, John C; Ramenofsky, Marilyn

2016-08-01

Appropriate timing of migratory behavior is critical for migrant species. For many temperate zone birds in the spring, lengthening photoperiod is the initial cue leading to morphological, physiological and behavior changes that are necessary for vernal migration and breeding. Strong evidence has emerged in recent years linking thyroid hormone signaling to the photoinduction of breeding in birds while more limited information suggest a potential role in the regulation of vernal migration in photoperiodic songbirds. Here we investigate the development and expression of the vernal migratory life history stage in captive Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) in a hypothyroidic state, induced by chemical inhibition of thyroid hormone production. To explore possible variations in the effects of the two thyroid hormones, triiodothyronine and thyroxine, we subsequently performed a thyroid inhibition coupled with replacement therapy. We found that chemical inhibition of thyroid hormones resulted in complete abolishment of mass gain, fattening, and muscle hypertrophy associated with migratory preparation as well as resulting in failure to display nocturnal restlessness behavior. Replacement of thyroxine rescued all of these elements to near control levels while triiodothyronine replacement displayed partial or delayed rescue. Our findings support thyroid hormones as being necessary for the expression of changes in morphology and physiology associated with migration as well as migratory behavior itself. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypopituitarism in the elderly in the presence of elevated thyroid stimulating hormone levels.

PubMed Central

Beringer, T.; McClements, B.; Weir, I.; Gilmore, D.; Kennedy, L.

1988-01-01

Two cases of primary hypothyroidism with hypopituitarism in elderly patients are reported. The elevated levels of thyroid stimulating hormone led to delay in the recognition of accompanying pituitary failure. Elderly patients should not be commenced on thyroxine replacement therapy until the possibility of hypopituitarism and cortisol deficiency has been excluded. PMID:3256811

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

PubMed

Giannakopoulos, Aris; Katelaris, Anni; Noni, Maria; Karakonstantakis, Theodore; Kanaka-Gantenbein, Christina; Doudounakis, Stavros

2018-05-01

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Is Parenteral Levothyroxine Therapy Safe in Intractable Hypothyroidism?

PubMed

Peynirci, Hande; Taskiran, Bengur; Erturk, Erdinc; Sisman, Pınar; Ersoy, Canan

2018-06-01

A 32-year old woman was admitted to the hospital due to intractable hypothyroidism refractory to high dose of oral l-thyroxine therapy. She underwent total thyroidectomy and radioactive iodine therapy due to papillary thyroid cancer. After excluding poor adherence to therapy and malabsorption, levothyroxine absorption test was performed. No response was detected. Transient neurologic symptoms developed during the test. She developed 3 attacks consisting of neurologic symptoms during high dose administration. The patient was considered a case of isolated l-thyroxine malabsorption. She became euthyroid after intramuscular twice weekly l-thyroxine therapy. There are a few case reports regarding isolated l-thyroxine. We report successful long term results of twice weekly administered intramuscular l-thyroxine therapy. We also draw attention to neurologic side effects of high dose l-thyroxine therapy. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans.

PubMed

Fish, L H; Schwartz, H L; Cavanaugh, J; Steffes, M W; Bantle, J P; Oppenheimer, J H

1987-03-26

A change in the formulation of the levothyroxine preparation Synthroid (Flint) in 1982 prompted us to reevaluate the replacement dose of this drug in 19 patients with hypothyroidism. The dose was titrated monthly until thyrotropin levels became normal. The mean replacement dose (+/- SD) was 112 +/- 19 micrograms per day, significantly less (P less than 0.001) than the dose of an earlier formulation--169 +/- 66 micrograms per day--used in a similar study (Stock JM, et al. N Engl J Med 1974; 290:529-33). The fractional gastrointestinal absorption of a tablet of the current formulation is 81 percent, considerably higher than the earlier estimate of 48 percent. Using high-performance liquid chromatographic analysis, we found that the current tablet contains the amount of thyroxine stated by the manufacturer. By measuring the bioavailability of the earlier type of tablet in five patients, we inferred that the strength of the previous tablet had been overestimated. In the present study, the thyrotropin levels of patients on replacement therapy returned to normal when serum triiodothyronine concentrations were not significantly different from those of controls (122 vs. 115 ng per deciliter [1.87 vs. 1.77 nmol per liter]), but when serum thyroxine levels were significantly above those of controls (11.3 vs. 8.7 micrograms per deciliter [145 vs. 112 nmol per liter], P less than 0.001). These findings suggest the possibility that in humans, serum triiodothyronine may play a more important part than serum thyroxine in regulating the serum thyrotropin concentration.

Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.

PubMed

Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

2018-04-01

Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients. This was a retrospective cohort study of adult patients with advanced nonthyroidal cancer treated with TKI and available thyroid function testing at three affiliated academic hospitals from 2000 to 2017. Patients with preexisting thyroid disease were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid status with TKI treatment was determined from thyroid function testing and initiation of thyroid medication, and classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement). Multivariate models were used to evaluate the effect of TKI-related hypothyroidism on overall survival (OS). Of 1120 initial patients, 538 remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%) patients with TKI therapy. Patients with hypothyroidism had significantly longer OS, with median OS in euthyroid patients of 685 days [confidence interval (CI) 523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991] in OH patients (p < 0.0001). After adjustment for age, sex, race/ethnicity, cancer type, cancer stage, ECOG performance status, and checkpoint inhibitor therapy, OH remained significantly associated with OS (hazard ratio = 0.561; p < 0.0001), whereas SCH did not (hazard ratio = 0.796; p = 0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement. New hypothyroidism in cancer patients treated with TKI is associated with significantly improved OS, should not necessitate TKI dose reduction or discontinuation, and may provide independent prognostic information.

Effect of L-thyroxine treatment versus a placebo on serum lipid levels in patients with sub-clinical hypothyroidism

PubMed Central

Li, Xue; Meng, Zhaowei; Jia, Qiang; Ren, Xiaojun

2016-01-01

Sub-clinical hypothyroidism is a common disease and whether L-thyroxine replacement treatment improves serum lipid levels in affected patients remains controversial. Thus, the aim of the present meta-analysis was to assess the effect of L-thyroxine therapy on serum lipid levels in sub-clinical hyperthyroidism. Relevant randomized controlled trials (RCTs) containing continuous data, published until July 2015 were retrieved from the Cochrane Library, PubMed, Medline, Google Scholar and Embase databases and subjected to meta-analysis using Review Manager software version 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark). Seven RCTs comprising 319 patients were included. The overall methodological quality of the RCTs was good. Statistical analysis revealed that serum low-density lipoprotein-cholesterol (LDL-C) levels were significantly decreased after L-thyroxine treatment [mean difference (MD): −0.23; 95% confidence interval: −0.44, −0.03; P=0.02], while changes of total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) were not significant (MD: −0.18, P=0.09; MD: −0.02, P=0.78; and MD: −0.06, P=0.14, respectively). In conclusion, the meta-analysis performed in the present study revealed that compared with placebo treatment, L-thyroxine significantly improved serum LDL-C levels in patients with sub-clinical hypothyroidism, while not significantly affecting TC, TG and HDL-C levels. PMID:27699011

Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism in dogs.

PubMed

Williams, D A; Scott-Moncrieff, C; Bruner, J; Sustarsic, D; Panosian-Sahakian, N; Unver, E; el Shami, A S

1996-11-15

To validate a new immunoradiometric assay for canine thyroid-stimulating hormone (cTSH) and to document changes in serum cTSH concentration during induction of hypothyroidism in dogs. Six healthy adult male Beagles. Sensitivity, specificity, precision, and accuracy of the cTSH assay were evaluated in vitro. Hypothyroidism was induced in dogs by i.v. administration of sodium iodide I 131 solution. Subsequently, L-thyroxine was administered orally to normalize serum thyroxine concentrations. The cTSH assay appeared to be specific and was sufficiently sensitive to detect cTSH in the serum of these dogs prior to induction of hypothyroidism. There was a 35-fold increase in mean serum cTSH concentration following induction of hypothyroidism, and 35 days after initiation of thyroid replacement therapy, mean serum cTSH concentration was not significantly greater than mean baseline value. Assay of serum cTSH is likely to prove helpful in the differential diagnosis of primary, secondary, and tertiary hypothyroidism in dogs, and in monitoring response to thyroid hormone replacement treatment.

Acute myocardial infarction during l-thyroxine therapy in a patient with intermittent changing axis deviation, permanent atrial fibrillation and without significant coronary stenoses.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-01-07

It has been rarely reported intermittent changing axis deviation also occurs during atrial fibrillation. Intermittent changing axis deviation during acute myocardial infarction and changing axis deviation associated with atrial fibrillation and acute myocardial infarction too have been also rarely reported. It has also been reported acute myocardial infarction during l-thyroxine substitution therapy in a patient with elevated levels of free triiodothyronine and without significant coronary artery stenoses. An acute myocardial infarction due to coronary spasm associated with l-thyroxine therapy has also been reported too. We present a case of changing axis deviation during acute myocardial infarction in a 56-year-old Italian woman with permanent atrial fibrillation and l-thyroxine therapy and without significant coronary stenoses. Also this case focuses attention on changing axis deviation in the presence of atrial fibrillation during acute myocardial infarction and on the possible development of acute myocardial infarction without significant coronary stenoses associated with l-thyroxine therapy.

Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

PubMed

Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

2016-01-01

Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p < 0.001). There was a significant positive correlation between baseline serum thyroid stimulating hormone (TSH) level and EAT thickness in the SCH group. There was a significant reduction in mean EAT thickness in response to L-thyroxine treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p < 0.001). The decrease in EAT thickness after L-thyroxine treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

PubMed

Yu, Jing; Tian, Ai-Juan; Yuan, Xin; Cheng, Xiao-Xin

2016-01-01

Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.

Thyroid aplasia in male sibling of heterozygotic twins born to the hyperthyroid mother treated with propylthiouracil during pregnancy (case report).

PubMed

Almarzouki, A A

2012-01-01

A 30-year-old pregnant female was diagnosed to have thyrotoxicosis (TSH= 0.005 µU/ml) at 13th week of gestation. Propylthiouracil (PTU; 200 mg daily) was prescribed to her and four weekly follow ups by the endocrinologist and obstetrician were ensured. At each examination TSH, FT4 and FT3 levels were normal and she became symptom free. Repeated ultrasound examination throughout the pregnancy did not reveal any fetal abnormality. The lady normally delivered heterozygotic twins. Umbilical cord blood of the baby boy twin showed a high TSH (541 µU/ml; reference range 0.270 - 4.20 μU/ml). He was started on thyroxine therapy (50 µg once daily). Ultrasound reported the absence of the thyroid gland. One month later TSH was within normal range and thyroxine dose was adjusted to 25 µg once daily. Repeated ultrasound confirmed the absence of thyroid gland. TSH was repeatedly normal. The boy is currently doing well on thyroxine replacement therapy. The other non-identical twin was a healthy girl with normal thyroid function tests and always thereafter. This case report suggested that PTU could be a hazardous drug to the fetus, since the mother gave birth to a baby with thyroid aplasia. PTU, Thyroid aplasia, Thyrotoxicosis, TSH.

Acute psychosis as a presentation of hypopituitarism

PubMed Central

Kate, Shruti; Dhanwal, Dinesh Kumar; Kumar, Shishir; Bharti, Praveen

2013-01-01

Acute onset neuropsychiatric manifestations in hypopituitarism are uncommon. We report a case of a 60-year-old man who was a follow-up case of macroprolactinoma with hypopituitarism for the last 9 years. He was on medical treatment with cabergoline, thyroxine and depot testosterone. During the last 2 years he was non-adherent to medications especially cabergoline. He was hospitalised for 2 days through emergency services following acute onset psychosis. His pituitary hormone profile was suggestive of adrenal insufficiency, secondary hypothyroidism and hypogonadism. MRI of the hypothalamic pituitary region revealed a pituitary macroadenoma which was larger in size compared to the previous scan. Further, this lesion was compressing on the adjoining structures including optic chiasma. The patient was treated with intravenous fluids, hydrocortisone and thyroxine replacement therapy. With this treatment he completely recovered from psychosis within 48 h. PMID:23853186

Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

PubMed

Tigas, S; Idiculla, J; Beckett, G; Toft, A

2000-12-01

There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium.

PubMed

Le Traon, G; Burgaud, S; Horspool, L J I

2008-04-01

Oral L-thyroxine (L-T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of L-T4 following administration of a solution (Leventa) was investigated in healthy dogs. L-T4 was absorbed fairly rapidly (t(max) 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 microg L-T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of L-T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with L-T4 oral administration delayed L-T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of L-T4 following administration of a tablet formulation was about 50% of that of the L-T4 solution. The pharmacokinetic properties of liquid L-T4 after oral administration support the use of a dose rate of 20 microg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.

Lymphocutaneous Sporotrichosis Treated with Potassium Iodide with Development of Subclinical Hypothyroidism: Wolff-Chaikoff Effect?

PubMed

Arora, Pooja; Raihan, M; Kubba, Asha; Gautam, Ram K

2017-01-01

Sporotrichosis is a subcutaneous mycotic infection caused by Sporothrix schenckii that is acquired by traumatic implantation. The diagnosis is established by demonstration of fungal elements on histopathology and culture. Potassium iodide, azole antifungals, and terbinafine are the treatment options available. In this article, we report a 60-year-old female with lymphocutaneous sporotrichosis that responded well to potassium iodide. However, subclinical hypothyroidism (Wolff-Chaikoff effect) was encountered as a side effect of therapy which was managed with thyroxine replacement. Knowledge about the Wolff-Chaikoff effect (WCE) is important for the dermatologist and reinforces the need for screening and monitoring of thyroid stimulating hormone (TSH) in patients where long duration therapy is being planned.

Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials.

PubMed

Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A; Humayun, Choudhry; Khan, Idrees M; Adus, Ali; Rasool, Aisha; Veledar, Emir; Nasir, Khurram

2017-07-01

Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima-media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. CIMT was significantly higher among SCH (n=280) as compared to EU controls (n=263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p=0.004; I 2 =65%. After treatment with thyroxin in subjects with SCH (n=314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD －0.32; 95% CI (－0.47, －0.16), p=＜0.0001; I 2 =2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (－0.04, 0.30); p=0.14; I 2 =27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis.

Effect of Thyroxin Treatment on Carotid Intima–Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials

PubMed Central

Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A.; Humayun, Choudhry; Khan, Idrees M.; Adus, Ali; Rasool, Aisha; Veledar, Emir

2017-01-01

Aim: Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima –media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Methods: Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. Results: CIMT was significantly higher among SCH (n = 280) as compared to EU controls (n = 263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p = 0.004; I2 = 65%. After treatment with thyroxin in subjects with SCH (n = 314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD −0.32; 95% CI (−0.47, −0.16), p = < 0.0001; I2 = 2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (−0.04, 0.30); p = 0.14; I2 = 27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. Conclusion: This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis. PMID:28566564

Laparoscopic sleeve gastrectomy leads to reduction in thyroxine requirement in morbidly obese patients with hypothyroidism.

PubMed

Aggarwal, Sandeep; Modi, Shrey; Jose, Toney

2014-10-01

The impact of laparoscopic sleeve gastrectomy (LSG) on various co-morbidities including type II diabetes mellitus, hypertension, and sleep apnea is well established. However, its effect on hypothyroidism has not been given due attention evidenced by the scant literature on the subject. The purpose of this report is to assess the change in thyroxine (T4) requirement in morbidly obese patients with clinical hypothyroidism after LSG. We conducted a retrospective review of morbidly obese patients on T4 replacement therapy for clinical hypothyroidism who underwent LSG from August 2009 to July 2012 at our institution. Of the 200 patients who underwent LSG during this period, 21 (10.5 %) were on T4 replacement therapy preoperatively for clinical hypothyroidism. Two patients were lost to follow-up. The remaining 19 patients were categorized into two groups. Group 1 comprised 13 patients with decreased T4 requirements after LSG. Group 2 comprised six patients in whom the T4 dose remained unaltered. The mean change in T4 requirement in group 1 was 42.07 % (12-100 %). Group 1 patients had a significantly higher mean preoperative body mass index (48.7 vs. 43.0 kg/m(2); p = 0.03) than the group 2 patients. There was a significant correlation between the percentage excess weight loss and the percentage change in T4 requirement in group 1 (r = 0.607, p = 0.028). Sleeve gastrectomy has a favorable impact on hypothyroid status as seen by a reduction in T4 requirement in the majority of morbidly obese patients with overt hypothyroidism.

Follow-up of congenital heart disease patients with subclinical hypothyroidism.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna

2015-08-01

Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years - 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report.

PubMed

Marzuillo, Pierluigi; Grandone, Anna; Perrotta, Silverio; Ruggiero, Laura; Capristo, Carlo; Luongo, Caterina; Miraglia Del Giudice, Emanuele; Perrone, Laura

2016-06-18

In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

[The importance of bisoprolol in prevention of heart left ventricular hypertrophy in patients with long term L-thyroxin suppressive therapy, after the operation of differentiated thyroid carcinoma].

PubMed

Matuszewska, Gabriela; Marek, Bogdan; Kajdaniuk, Dariusz; Przywara-Chowaniec, Brygida; Jarzab, Jerzy; Jarzab, Barbara

2007-01-01

Patients with differentiated thyroid carcinoma have to undergo radical surgical treatment, which includes total thyreoidectomy, radioiodine therapy and a life-time suppressive therapy with L-thyroxine. The aim of this study was a prospective evaluation of left ventricular hypertrophy during L suppressive-thyroxine treatment in patients treated for differentiated thyroid carcinoma. The examined group comprised 50 patients with differentiated thyroid carcinoma, treated by total thyroidectomy and 131I therapy. Echocardiographic measurements were needed for estimation of left ventricular mass and its index, according to recommendations of American Echocardiography Society. During two-years long suppressive therapy we observed a significant rise in left ventricular mass. In woman group left ventricular mass was increased from 168+/-39 g to 204+/-45 g (p<0.001) and in men from 205+/-60 to 320+/-21 g. Likewise, left ventricular mass index was increased in women group from 96+/-18 g/m(2) to 116+/-25 g/m(2) (p<0.001) and in men group from 107+/-37 g/m(2) to 158+/-28 g/m(2). Simultaneous treatment with bisoprolol caused a regression of left myocardial hypertrophy. Already after 6 months of simultaneous treatment with L-thyroxin and bisoprolol, for left ventricular mass was reduced to normal: in woman 165+/-35 g, and in men to 178+/-38 g. Analogous results were obtained left ventricular mass index. After 6 months it was reduced to 94+/-12 g/m(2) in woman and in men to 132+/-32 g/m(2). 1. In differentiated thyroid cancer patients, treated postoperatively with L-thyroxine suppressive therapy, left ventricular hypertrophy is observed already during the first year of suppressive therapy and progresses during the next year of treatment. 2 Addition of a beta-adrenergic antagonist to suppressive doses of L-thyroxine causes a regression of left ventricular hypertrophy, thus, beta-adrenergic antagonists should be administered in this group of patients.

Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation.

PubMed

Sant'Anna, Ricardo; Almeida, Maria Rosário; Varejāo, Nathalia; Gallego, Pablo; Esperante, Sebastian; Ferreira, Priscila; Pereira-Henriques, Alda; Palhano, Fernando L; de Carvalho, Mamede; Foguel, Debora; Reverter, David; Saraiva, Maria João; Ventura, Salvador

2017-03-24

More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T 4 ) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T 4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies.

A novel EGFR-TKI inhibitor (cAMP-H3BO3complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes

PubMed Central

Tong, Yongpeng; Huang, Chunliu; Zhang, Junfang

2017-01-01

Purpose Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. Results The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro. Compared to the negative control, tumor growth was significantly suppressed in mice treated with oxidative phosphorylation uncoupler thyroxine sodium and either cAMP-H3BO3 complex or cAMP-H3BO3 complex (P < 0.05). Moreover, the body temperature increase induced by treatment with thyroxine sodium inhibited tumor growth. Immunohistochemical analyses showed that A549 cell apoptosis was significantly higher in the cAMP-H3BO3 complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca2+ content analysis showed that the Ca2+ content of tumor tissue was significantly higher in the cAMP-H3BO3 complex plus thyroxine sodium treatment group than in other groups. Materials and Methods Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-H3BO3 complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-H3BO3 complex) with or without an oxidative phosphorylation uncoupler (thyroxine sodium) was investigated in vitro and in a nude mouse xenograft lung cancer model incorporating human A549 cells. Conclusions cAMP-H3BO3 complex is a novel EGFR-TKI. Combination therapy using cAMP-H3BO3 with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes. PMID:28915593

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine.

PubMed

Adamarczuk-Janczyszyn, Maria; Zdrojowy-Wełna, Aleksandra; Rogala, Natalia; Zatońska, Katarzyna; Bednarek-Tupikowska, Grażyna

2016-01-01

Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

PubMed

Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

2017-04-01

Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

PubMed

Guglielmi, Rinaldo; Frasoldati, Andrea; Zini, Michele; Grimaldi, Franco; Gharib, Hossein; Garber, Jeffrey R; Papini, Enrico

2016-11-01

Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

Laparoscopic gastric bypass in patients on thyroid replacement therapy for subnormal thyroid function - prevalence and short-term outcome.

PubMed

Szomstein, Samuel; Avital, Shmuel; Brasesco, Oscar; Mehran, Amir; Cabral, Jose M; Rosenthal, Raul

2004-01-01

Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.

The effects of treatment on lipoprotein subfractions evaluated by polyacrylamide gel electrophoresis in patients with autoimmune hypothyroidism and hyperthyroidism.

PubMed

Minarikova, Zuzana; Gaspar, Ludovit; Kruzliak, Peter; Celecová, Zuzana; Oravec, Stanislav

2014-10-10

Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

Review of Heterotopic Thyroid Autotransplantation

PubMed Central

Sakr, Mahmoud; Mahmoud, Ahmed

2017-01-01

Total thyroidectomy is increasingly accepted for the management of bilateral benign thyroid disorders. Postoperatively, patients require lifelong levothyroxine replacement therapy to avoid postoperative hypothyroidism, which besides the burden of compliance, has been proven to be associated with several long-term side effects. Heterotopic thyroid autotransplantation was proposed several decades ago to avoid the need for life-long postoperative replacement therapy with maintaining the autoregulatory mechanism of thyroxin production inside the body according to its needs. Available data regarding this topic in literature is relatively poor. Before applying thyroid autotransplantation on humans, several studies have been done on animals, where the autologous transplantations were found to be successful in almost all the cases, proved by follow up postoperative 8-week measurements of thyroid hormones and histopathological examination of the removed autografts. Regarding the clinical application, few trials have been done using cryopreserved in vivo, in vitro or immediately autotransplanted thyroid autografts. Satisfactory results were obtained, however, the number of these studies and the number of patients per each study was very low. Besides the study methodologies were not so consistent. PMID:28535579

Hypothyroidism following treatment for head and neck cancer

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

Vrabec, D.P.; Heffron, T.J.

One hundred ninety-six head and neck patients were studied to determine the effects of radiation therapy and surgery on thyroid function. Serum thyroid-stimulating hormone (TSH) levels were obtained as a screening test for primary hypothyroidism. Elevated TSH levels were found in 57 of the 196 patients (29.1%). The highest incidence of abnormal TSH values (66%) occurred in the group treated with combination radiation therapy and surgery, including partial thyroidectomy. TSH levels rose early in the posttreatment period with 60% of the abnormal values occurring within the first three posttreatment years. Posttreatment thyroid dysfunction was twice as common in women (48.6%)more » as in men (25.4%). When serum thyroxine levels by radioimmunoassay (T4RIA) were correlated with the elevated serum TSH levels, a similar pattern was seen with 65% of the patients in Group 3 having a decreased T4RIA level indicating overt hypothyroidism. Pretreatment levels of thyroid function including thyroid antibody studies should be established for all patients. Serial TSH levels should be done every three months during the first three posttreatment years and semiannually thereafter as long as the patient will return for follow-up care. All patients treated with combination radiation therapy and surgery who develop elevated TSH levels should be treated with thyroid replacement therapy. Patients receiving radiation therapy alone should receive replacement thyroid therapy if they develop a depressed T4RIA value or a pattern of gradually increasing TSH levels.« less

[Relationship between hypothyroidism and cholesterol out of the records of 1756 patients].

PubMed

Sampaolo, Guido; Campanella, Nando; Catozzo, Vania; Ferretti, Maurizio; Vichi, Giovanna; Morosini, Pierpaolo

2014-02-01

Subclinical hypothyroidism (SH) is settled whenever high levels of serum thyroid-stimulating hormone (TSH) are detected, whereas free thyroid hormone levels are within the normal range. Benefits and risks of therapy for SH have been debated for 2 decades. However, consensus has not yet been achieved. Besides preventing the progression to overt hypothyroidism, the decision of undertaking replacement therapy in SH is made mainly by basing on the risk of metabolic (dyslypidemia) and subsequent cardiovascular complications. A series, made up of 1756 patients (mean age 42,8±16,8, range 0,5-94) and filed from 1984 to 2013, was studied retrospectively. 169 patients were affected by clinical (overt) hypothyroidism (IC: TSH >40). 1587 patients were affected by SH, out of whom 1121 were mild (TSH <10) and 466 medium (TSH ≥ 10 ≤40). The series of patients was properly followed-up. The mean follow-up time was 6 years. In all patients TSH, Ft4, and total cholesterol were evaluated basally and after appropriate (TSH normalized) medical therapy. By medical replacement treatment, clinical hypothyroidism (CI) related hypercholesterolemia decreased significantly in 28%. In SH, the baseline serum cholesterol levels were wide. However, replacement treatment did not reduce such levels. No major cardiovascular accident occurred to any patient over the follow-up period. Hypercholesterolemia is certainly due to CI, therapy reduces cholesterol levels that not always fall below 200 mg/dl and this condition persists over time. SH is not characterized by hypercholesterolemia. Cholesterol levels in these patients are variable equal to the normal people and can not be reduced with thyroxine.

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.

[Hypothyroidism-when and how to treat?

PubMed

Koehler, V F; Reincke, M; Spitzweg, C

2018-06-05

The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT 4 ) and triiodothyronine (fT 3 ) levels, while in manifest hypothyroidism serum fT 4 and fT 3 levels are reduced. Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. Initiation of levothyroxine (T 4 ) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities. Treatment of patients with subclinical hypothyroidism is still a controversial topic. In general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70 years is clearly indicated if the TSH concentration is >10 mU/l. Standard of care for treatment of hypothyroidism is T 4 monotherapy. The biochemical treatment goal for T 4 replacement in primary hypothyroidism is a TSH level within the reference range (0.4-4.0 mU/l). In contrast, in secondary hypothyroidism, serum fT 4 levels are the basis for adjusting thyroid hormone dosage. Inadequate replacement of T 4 resulting in subclinical or even manifest hyperthyroidism should urgently be avoided. T 4 /liothyronine (T3) combination therapy is still a matter of debate and not recommended as standard therapy, but may be considered in patients with persistence of symptoms, despite optimal T 4 treatment, based on expert opinion.

Hepatic amino nitrogen conversion and organ N-contents in hypothyroidism, with thyroxine replacement, and in hyperthyroid rats.

PubMed

Grøfte, T; Wolthers, T; Jensen, D S; Møller, N; Jørgensen, J O; Orskov, H; Vilstrup, H

1997-02-01

The role of thyroid hormones in the regulation of hepatic conversions of amino nitrogen to urea is unresolved. The present study was designed to assess ureagenesis in rats with experimentally well-established hypo- and hyperthyroidism. The possible role of propylthiuracil (PTU), used for induction of hypothyroidism, was ascertained during thyroxine replacement of PTU treated hypothyroid rats. Basal blood amino nitrogen concentrations (AAN), the urea nitrogen synthesis rate (UNSR) and the maximal hepatic capacity for urea nitrogen synthesis (CUNS) obtained during alanine infusion were determined together with N-contents in the soleus muscle and kidneys in experimentally hypothyroid rats (n = 19), upon thyroxine replacement (n = 14) and in experimentally hyperthyroid rats (n = 19). Hypothyroidism was induced by adding propylthiouracil (0.05%) to the drinking water for 5 weeks. Hyperthyroidism was induced by thyroxine 100 micrograms/100 g body weight. During hyperthyroidism, T3 fell to less than 10%, food intake was halved, and body weight fell by 13%. Basal blood AAN fell by 25% (p < 0.01), UNSR more than doubled (p < 0.01), and CUNS rose by 45% (p < 0.05). N-contents of the soleus muscle fell by 13% and by 20% in kidneys, respectively (p < 0.05). Thyroxine replacement normalized AAN, UNSR, CUNS and reduced N-loss to 7% in the soleus muscle (NS) and kidneys (p < 0.05), respectively. During hyperthyroidism, T3 rose five-fold, food intake rose by two thirds, and body weight fell by 10%. Basal AAN rose by 20% (p < 0.05), UNSR doubled (p < 0.01), and CUNS rose by 25% (p < 0.05). N-contents of the soleus muscle decreased by 19%, whereas kidney N-contents increased by 25% (p < 0.05). Overall liver function assessed by galactose elimination capacity did not differ among groups. Both conditions increased the rate of urea synthesis; in the hypothyroid state the hepatic waste of amino-N was limited by low blood concentration of amino-N, probably due to lower proteolysis. In the hyperthyroid state hepatic amino-N loss was aggravated by higher blood concentration of amino-N, probably due to higher proteolysis. This difference may explain the markedly different dietary nitrogen economy between the two groups. The findings suggest that distinct hepatic acceleration of urea synthesis may contribute to the protein loss seen in both myxedema and in thyrotoxicosis in humans.

Childhood thyromegaly: recent developments

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

Reiter, E.O.; Root, A.W.; Rettig, K.

1981-10-01

Evaluation of a child with goiter includes historical review, physical examination, and measurement of serum concentrations of PBI, T4 and T3RU, TSH, and titers of antithyroglobulin and antithyroid microsomal antibodies. If there are no indications for more intensive evaluation such as history of cervical irradiation, a palpable abnormality of the thyroid gland or unusual laboratory findings (e.g., a significant PBI-thyroxine iodine discrepancy in the absence of a positive antithyroid antibody titer), a trial of TSH-suppressive therapy with thyroxine is undertake, even if the cause of thyromegaly has not been identified. If thyroid size diminishes in the ensuing six to 12more » months, treatment is maintained for approximately two years and then discontinued. If the goiter recurs, or if there is impaired thyroid function, treatment is resumed. Periodically, antithyroid antibody titers and indices of thyroid function are determined. If the goiter does not diminish after a reasonable trial of suppressive therapy with adequate amounts of thyroxine (i.e., those quantities which will inhibit TRH-induced secretion of TSH), subtotal thyroidectomy is recommended to be certain that an underlying neoplasm has not been overlooked. A biopsy of the thyroid is not performed routinely in such children prior to operative therapy. Almost invariably, examination of the surgical specimen reveals CLT. Postoperatively, suppressive doses of thyroxine are maintained indefinitely. Inasmuch as thyroxine suppression of TSH secretion is essential in the management of patients with thyroid neoplasms, a limited medical trial, as described, does not place the patient at undue risk.« less

Long-term outcome of thyrotoxicosis in childhood and adolescence in the west of Scotland: the case for long-term antithyroid treatment and the importance of initial counselling.

PubMed

Kourime, Mariam; McGowan, Sheena; Al Towati, Mabrouka; Ahmed, S Faisal; Stewart, Graham; Williamson, Scott; Hunter, Iain; Donaldson, Malcolm D C

2017-12-21

Thyrotoxicosis is both rarer and more severe in children than in adults, rendering management difficult and often unsatisfactory. To ascertain outcome in a geographically defined area of Scotland between 1989 and 2014. Retrospective case note review with follow-up questionnaire to family doctors for patients with Graves' disease and Hashimoto's thyroiditis. Sixty-six patients (58 females:8 males) comprising 53 with Graves' disease and 13 with Hashimoto's thyroiditis were diagnosed at median 10.4 (2.9-15.8) years and followed up for 11.8 (2.6-30.2) years. Antithyroid drug (ATD) therapy was stopped electively in 35 patients after 4.5 (1.5-8.6) years, resulting in remission in 10/13 Hashimoto's thyroiditis and 10/22 Graves' disease. Side effects occurred in 12 patients receiving carbimazole, six of whom changed to propylthiouracil; no adverse events occurred in the latter patients.Second-line therapy was given to 37 patients (34 with Graves' disease), comprising radioiodine (22) at 15.6 (9.3-24.4) years for relapse (6), poor control/adherence (14) or electively (2); and surgery (16) at 12 (6.4-21.3) years for relapse (4), poor control/adherence (5) and electively (7). Adherence problems with thyroxine replacement were reported in 10/33 patients in adulthood. Hashimoto's thyroiditis should be distinguished from Graves' disease at diagnosis since the prognosis for remission is better. Remission rates for Graves' disease are low (10/53 patients), time to remission variable and adherence with both ATD and thyroxine replacement often problematic. We recommend (a) the giving of long-term ATD rather than a fixed course of treatment in GD and (b) meticulous and realistic counselling of families from the time of diagnosis onwards. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association of Hypothyroidism with Body Mass Index, Systolic Blood Pressure and Proteinuria in Diabetic Patients: Does treated Hypothyroidism with Thyroxine Replacement Therapy Prevent Nephropathy/Chronic Renal Disease?

PubMed

Aziz, Kamran M A

2016-01-01

Untreated or sub-clinical hypothyroidism is associated with insulin resistance, obesity, adverse effects on cardiovascular system, hypertension and in turn risk of nephropathy. However, these changes are reversible with thyroxine replacement therapy (TRT). Current research studied 4235 diabetic patients, divided into two groups, those with clinical hypothyroidism /on TRT, compared to those without thyroid disease or undiagnosed. BMI, blood pressure, creatinine, urine microalbumin and spot urine protein levels were compared between these two groups. Study finding demonstrated that for hypothyroid cases, BMI was higher (32.2 ± 7.44 versus 29.4 ± 5.7; p < 0.0001), serum creatinine was on lower levels (0.75 ± 0.27 versus 1.0 ± 0.74; p = 0.001), systolic BP was on lower side (123.7 ± 15.9 versus 128.13 ± 16.8; p= 0.015); spot urine microalbumin was on lower side (52.58 ± 71.65; versus 87.77 ± 140.86; p=0.010) and spot urine protein had lower levels (25.3 ± 38.3 versus 44.28 ± 123.58; p < 0.0001). Current research also demonstrated that Pearson`s x2 and odds/protective odds for hypothyroidism (on TRT) was strongly associated with obesity (p <0.0001; odds ratio 2.28, 95% CI 1.47 to 3.56). However, they were protected from HTN (p= 0.272; protective odds ratio 1.28, 95%CI 0.824 to 1.98), nephropathy (p=0.386; protective odds 1.36, 95% CI 0.861 to 2.14) and chronic renal disease (p= 0.112; protective odds 3.42, 95% CI 0.83 to 14.13). In conclusion, TRT itself has protective effects on cardiovascular and renal system. Hence, thyroid screening is essential among diabetics to detect sub clinical or clinical hypothyroidism.

Massive pericardial effusion without cardiac tamponade due to subclinical hypothyroidism (Hashimoto's disease).

PubMed

Papakonstantinou, Panteleimon E; Gourniezakis, Nikolaos; Skiadas, Christos; Patrianakos, Alexandros; Gikas, Achilleas

2018-05-01

Hypothyroidism is a significant cause of pericardial effusion. However, large pericardial effusions due to hypothyroidism are extremely rare. Hormone replacement therapy is the cornerstone of treatment for hypothyroidism and regular follow-up of patients after initiation of the therapy is indicated. Herein, the case of a 70-year-old woman with a massive pericardial effusion due to Hashimoto's disease is presented. A 70-year-old female from a rural village on the island of Crete, Greece, was admitted to our hospital due to a urinary tract infection. She was under hormone replacement therapy with levothyroxine 100 µg once a day for Hashimoto's disease. Two years previously, the patient had had an episode of pericarditis due to hypothyroidism and had undergone a computed tomography-guided pericardiocentesis. The patient did not have regular follow-up and did not take the hormone replacement therapy properly. On admission, the patient's chest X-ray incidentally showed a possible pericardial effusion. The patient was referred for echocardiography, which revealed a massive pericardial effusion. Beck's triad was absent. Thyroid hormones were consistent with subclinical hypothyroidism: thyroid-stimulating hormone (TSH) 30.25 mIU/mL (normal limits: 0.25-3.43); free thyroxin 4 0.81 ng/dL (normal limits: 0.7-1.94). The patient had a score of 5 on the scale outlined by the European Society of Cardiology (ESC) position statement on triage strategy for cardiac tamponade and, despite the absence of cardiac tamponade, a pericardiocentesis was performed after 48 hours. The patient was treated with 125 µg levothyroxine orally once daily. This was a rare case of an elderly female patient from a rural village with chronic massive pericardial effusion due to subclinical hypothyroidism without cardiac tamponade. Hypothyroidism should be included in the differential diagnosis of pericardial effusion, especially in a case of unexplained pericardial fluid. Initiation of hormone replacement therapy should be personalised in elderly patients. TSH levels >10 mU/L usually require therapy with levothyroxine in order to prevent adverse events. Rural patients usually do not have regular follow-up after the initiation of hormone replacement therapy. Pericardial effusions due to hypothyroidism grow slowly and subclinical hypothyroidism rarely shows signs and symptoms and can be underdiagnosed. The ESC position statement on triage strategy for pericardial diseases is a valuable clinical tool to estimate the necessity for pericardial drainage in such cases.

A simple test of one minute heart rate variability during deep breathing for evaluation of sympatovagal imbalance in hyperthyroidism.

PubMed

Shuvy, Mony; Arbelle, Jonathan E; Grosbard, Aviva; Katz, Amos

2008-01-01

Heart rate variability is a sensitive marker of cardiac sympathetic activity. To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV. Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing. One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 +/- 10.5 vs. 34.3 +/- 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups. Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.

Hypothesis: Persistently normal TSH levels may be used to recognize patients with transient forms of hypothyroidism and to suggest treatment withdrawal.

PubMed

Tandeter, H; Fraenkel, M

2018-07-01

There are no text-book recommendations on when or if treatment should or could be stopped in patients with a diagnosis of hypothyroidism, and these patients usually receive lifelong thyroxine therapy (despite the fact that some of them may have forms of transient hypothyroidism that will later recover function). Since TSH fluctuations during thyroxine treatment are common and a lack of this fluctuation might be used to identify patients who no longer need thyroxine treatment, we hypothesize that by offering patients with persistently controlled TSH levels a withdrawal trial of thyroxine treatment we may identify those who no longer need life-long treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Van Wyk Grumbach Syndrome: A Rare Consequence of Hypothyroidism.

PubMed

Reddy, Pavan; Tiwari, Kritika; Kulkarni, Abhishek; Parikh, Ketan; Khubchandani, Raju

2018-05-19

Long standing hypothyroidism presenting as an ovarian mass has been well described in literature as the Van Wyk Grumbach syndrome (hypothyroidism, isosexual precocious puberty and ovarian mass). Here, authors report this entity in a 11 y 7 mo old girl child who was referred to a surgeon in view of intestinal obstruction along with a multiloculated ovarian cyst. On evaluation, she was found to have raised serum creatinine, short stature, delayed bone age and pituitary enlargement. She was diagnosed with autoimmune thyroiditis and was started on replacement therapy with thyroxine, after which the ovarian cysts regressed. This entity should be kept in mind in cases of ovarian cysts, especially those with isosexual precocity, to prevent unnecessary evaluation and surgical misadventures.

Amiodarone-induced myxoedema coma.

PubMed

Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

2014-04-12

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3-5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.

Optimizing treatment of hypothyroidism.

PubMed

Clarke, Nick; Kabadi, Udaya M

2004-01-01

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

Successful treatment of refractory TAFRO syndrome with elevated vascular endothelial growth factor using thyroxine supplements.

PubMed

Oka, Satoko; Ono, Kazuo; Nohgawa, Masaharu

2018-04-01

Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism.

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.

A 6-year follow-up of a randomized prospective trial comparing methimazole treatment with or without exogenous L-thyroxine in Chinese patients with Graves' disease.

PubMed

Liu, X; Qiang, W; Liu, X; Liu, L; Liu, S; Gao, A; Gao, S; Shi, B

2014-11-01

Antithyroid drug therapy is one of the main medical treatments for Graves' disease. There have been conflicting reports as to whether the addition of exogenous L-thyroxine improves remission rates more than antithyroid drugs alone. This randomized, controlled and prospective clinical trial was undertaken to investigate the long-term outcome of methimazole treatment with or without exogenous L-thyroxine in Chinese patients. 145 patients with Graves' disease were randomly divided into 3 groups and all patients initially received 30 mg of methimazole daily for at least 1 month and then followed the titration -regimen with or without L-thyroxine: group 1 (30 mg→20 mg→15 mg→10 mg→5 mg); group 2 (30 mg→20 mg→15 mg→10 mg+L-thyroxine→5 mg+L-thyroxine); group 3 (30 mg→20 mg→15 mg→10 mg+L-thyroxine→5 mg+L-thyroxine→2.5 mg+L-thyroxine). The drug therapy was discontinued after 5 months of the final dose. 16 out of 46 patients in group 1 (34.8%), 12 out of 47 in group 2 (25.5%) and 16 out of 52 in group 3 (30.8%) had a recurrence of Graves' disease within 6-year follow-up after drug withdrawal. Survival Analysis showed no significant differences in the remission rates between any 2 groups, despite the remission rates in group 2 and 3 were slightly higher than that in group 1. The addition of L-thyroxine to methimazole treatment in patients with Graves' disease neither improves nor prevents the remission or recurrence of Graves' disease in China. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Reversible adrenal insufficiency and heterophile antibodies in a case of autoimmune polyendocrinopathy syndrome

PubMed Central

Kharb, Sandeep; Gundgurthi, Abhay; Dutta, Manoj K.; Garg, M. K.

2013-01-01

A 27-year-old male was admitted with diabetic ketoacidosis and altered sensorium with slurring of speech and ataxia. He was managed with intravenous insulin and fluids and later shifted to basal bolus insulin regimen and during further evaluation was diagnosed to be suffering from primary hypothyroidism and adrenal insufficiency. He was started on thyroxin replacement and steroids only during stress. After three months of follow up he was clinically euthyroid. His glycemic control was adequate on oral anti-hyperglycemic drugs and adrenal insufficiency recovered. However, his thyrotropin levels were persistently elevated on adequate replacement doses of thyroxin. His repeat TSH was estimated after precipitating serum with polyethylene glycol which revealed normal TSH. Here we report reversible adrenal insufficiency with hypothyroidism with falsely raised TSH because of presence of heterophile antibodies in a case of poly glandular endocrinopathy syndrome. PMID:24910843

Reversible adrenal insufficiency and heterophile antibodies in a case of autoimmune polyendocrinopathy syndrome.

PubMed

Kharb, Sandeep; Gundgurthi, Abhay; Dutta, Manoj K; Garg, M K

2013-12-01

A 27-year-old male was admitted with diabetic ketoacidosis and altered sensorium with slurring of speech and ataxia. He was managed with intravenous insulin and fluids and later shifted to basal bolus insulin regimen and during further evaluation was diagnosed to be suffering from primary hypothyroidism and adrenal insufficiency. He was started on thyroxin replacement and steroids only during stress. After three months of follow up he was clinically euthyroid. His glycemic control was adequate on oral anti-hyperglycemic drugs and adrenal insufficiency recovered. However, his thyrotropin levels were persistently elevated on adequate replacement doses of thyroxin. His repeat TSH was estimated after precipitating serum with polyethylene glycol which revealed normal TSH. Here we report reversible adrenal insufficiency with hypothyroidism with falsely raised TSH because of presence of heterophile antibodies in a case of poly glandular endocrinopathy syndrome.

The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study.

PubMed

Krysiak, R; Szkróbka, W; Okopień, B

2016-10-01

Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high-dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy. © Georg Thieme Verlag KG Stuttgart · New York.

[Analysis of changes in peripheral and central nervous system in irregularly treated adult patients with primary congenital hypothyroidism].

PubMed

Łacka, Katarzyna; Florczak, Jolanta; Gradecka-Kubik, Ilona; Rajewska, Justyna; Junik, Roman

2010-03-01

Lack of thyroid hormones in the womb and the first years of life causes changes in the nervous system and mental retardation. The aim of the study was to assess changes in peripheral and central nervous system in 29 adult patients with primary congenital hypothyroidism (PCH) depending on the cause of the disease and systematic treatment of L-thyroxine. The analysis was performed in 29 adult patients with PCH (16 women, 13 men) on the basis of the results of neurological examination, EEG, SPECT (Computer tomography single photon emission) of the brain. Changes in the nervous system were found in 72% of respondents. Patients who had implemented replacement therapy L-thyroxine after completing 12 months of age showed the most neurological disorders. There were variations in the cranial nerves III, IX, IV and VI. In 34% of respondents revealed paraneoplastic cerebellar symptoms, while the pyramid, and extrapyramidal symptoms in 10% and 3% of the people. EEG showed changes in brain bioelectrical activity in the entire study group. In the 83% found a significant asymmetry in regional cerebral blood flow (rCBF). Hypoperfusion outbreak occurred mainly in the stands and leading occipital. The relationship between time of initiation of treatment, and the presence of a systematic change in the nervous system was inversely proportional. In turn, analyzing the causes of most PCH deviations were found in the nervous system in patients with athyreosis. Brain SPECT study in these patients confirmed the organic changes in brain development. CONCLUSIONS. The presence and extent of changes in peripheral and central nervous system depends on the cause PCH, pending the implementation of L-thyroxine treatment and systematic. Studies of brain SPECT and EEG confirmed the existence of developmental changes of the brain in patients with PCH.

Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine.

PubMed

Escobar-Morreale, Héctor F; Botella-Carretero, José I; Morreale de Escobar, Gabriella

2015-01-01

At present, the drug of choice for the treatment of hypothyroidism is levothyroxine sodium, even though the thyroid gland secretes both thyroxine and 3',3,5-triiodothyronine; the latter is the more active of the two at the cellular level because of its higher affinity for the nuclear thyroid hormone receptors. To date, combined levothyroxine plus liothyronine treatment for hypothyroidism has been evaluated in 15 clinical trials in humans. In two studies, combined therapy seemed to have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone; in some of these studies, the patients preferred levothyroxine plus liothyronine combinations. This preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine. Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Thyroid status peculiarities of elderly patients 5 years after operation depending on the volume of surgical intervention].

PubMed

Aristarhov, V G; Danilov, N V; Aristarkhov, R V; Puzin, D A; Birykov, C V

2016-01-01

Long-term results of treatment of 180 patients operated 5 years ago for benign thyroid nodular pathology have been analyzed in the present paper, the results being analyzed depending on the volume of surgical intervention. The rate of postoperative hypothyrodism is lower in patients who had undergone limited thyroid resection, recurrent cases are more frequent, but they are not clinically significant and seldom require reoperation. It should also be noted that those patients have fewer cardiac complaints as the dose of hormone replacement therapy preparations is small. Elder patients who had undergone functionally significant thyroidectomy and need to take great doses of Thyroxin (107-150 mcg/day) have cardiac complaints more often (43 %) comparing to those who had undergone limited resections (35 %).

Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life.

PubMed

Tariq, Anam; Wert, Yijin; Cheriyath, Pramil; Joshi, Renu

2018-06-01

Hypothyroidism results in decreased mood and neurocognition, weight gain, fatigue, and many other undesirable symptoms. The American Association of Clinical Endocrinologists, the American Thyroid Association (ATA), and The Endocrine Society recommend levothyroxine (LT4) monotherapy as the treatment for hypothyroidism; however, after years of monotherapy, some patients continue to experience impaired quality of life. Combination LT4 and synthetic liothyronine (LT3) therapy or the use of desiccated thyroid extract (DTE), has not been suggested for this indication based on short-duration studies with no significant benefits. Our first observational study examined the role of combination therapy for 6 years in improving quality of life in a subset of a hypothyroid population without adverse effects and cardiac mortality. An observational retrospective study examining patients prescribed thyroid replacements with serum triiodothyronine (FT3), LT4 with LT3 (synthetic therapy) or DTE (natural therapy), compared with LT4 alone in the United States from 2010 to 2016. Thyroid-stimulating hormone (TSH), serum thyroxine (FT4), and FT3 levels were documented for each patient in addition to any admissions of myxedema coma, thyrotoxicosis, or cardiovascular complications, such as arrhythmias, atrial fibrillation, and mortality. At the conclusion of the study, a cross-sectional interview assessed quality of life for each combination therapy through the Medical Outcomes Study Short Form-20 questionnaire. Compared with patients taking only LT4, 89.47% using synthetic therapy had therapeutic TSH ( P < 0.05). Similarly, 96.49% using natural therapy had therapeutic TSH ( P < 0.05). Less than 5% of patients had supratherapeutic FT3. None of the patients who had abnormally low TSH or elevated FT3 or FT4 levels had hospitalizations for arrhythmias or thyrotoxicosis. On the Medical Outcomes Study Short Form-20 questionnaire, >92% answered feeling "excellent, very good, or good" when questioned about their health while undergoing thyroid replacement compared with levothyroxine alone. This is the only retrospective study reported to use long-term (mean 27 months) thyroid replacements with combination therapy and to compare between the two forms of therapy: synthetic and natural. For patients undergoing either therapy, we did not identify additional risks of atrial fibrillation, cardiovascular disease, or mortality in patients of all ages with hypothyroidism.

Amiodarone-induced myxoedema coma

PubMed Central

Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

2014-01-01

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3–5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8–1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25–756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease. PMID:24729111

Radioactive iodine ablation therapy: a viable option in the management of Graves' disease in Nigeria.

PubMed

Adedapo, K S; Fadiji, I O; Orunmuyi, A T; Onimode, Y; Osifo, B O A

2012-12-01

Graves' disease is an autoimmune disorder characterized by hyperthyroidism and associated features. Management of this disease condition for many decades has been largely by surgical and medical intervention. Usage of anti thyroid medication ameliorates the symptoms and effects of excessive production of thyroid hormones. Recently in Nigeria, Nuclear medicine facility became available with the option radioiodine ablative therapy for the management of Graves disease. This study highlights the benefits of radioiodine therapy against the background of equally viable medical and surgical practice. PATIENTS MATERIAL AND METHOD: All the 36 patients seen from the inception of Nuclear Medicine facility at the University College Hospital from June 2006 to May 2010 were included in this study. Sources of referral were compiled. All the patients were on anti thyroid medication at presentation. Thyroid scan was performed by Siemens E- cam gamma camera 20 minutes after intravenous injection of 3-5 mCi of Tc-99m-Pertechnetate. The patients with "diffuse toxic goiter" on thyroid scan were given 10 mCi of Iodine-131 orally and discharged home with radiosafety precautions. Most of the patients were treated 5 days post discontinuation of antithyroid medication. The patients were followed-up monthly with thyroid function tests to determine commencement of replacement therapy. Peak incidence of Graves' disease was at 6th decade (38.9%) of all patients studied. This disease was commoner in women with a ratio of 8 to 1. Ten (27.8%) patients became hypothyroid at the 3rd month post radioactive iodine-131 treatment, while the remaining 20 (55.6%) patients became hypothyroid at the 5th month. Six patients were lost to follow up. There was no recurrence of hyperthyroidism in all patients treated. Twenty eight (93.3%) patients were maintained on 100 mcg of levo-thyroxine daily, while 2 (6.7%) patients had more than 100 mcg of levo- thyroxine daily as maintenance dose. Radioactive iodine therapy presents a safe and effective alternative to the older conventional mode of management of Graves' disease

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

Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

PubMed

Bhatt, Parloop A; Makwana, Dharmesh

2008-02-01

The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

PubMed

Bakhshandeh, Mohsen; Hashemi, Bijan; Mahdavi, Seied Rabi Mehdi; Nikoofar, Alireza; Vasheghani, Maryam; Kazemnejad, Anoshirvan

2013-02-01

To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication. Copyright © 2013 Elsevier Inc. All rights reserved.

Echocardiographic evaluation of left ventricular diastolic dysfunction in subclinical hypothyroidism: A case-control study.

PubMed

Malhotra, Yuthika; Kaushik, Rajeev Mohan; Kaushik, Reshma

2017-08-01

To study the prevalence of left ventricular diastolic dysfunction (LVDD) in patients with subclinical hypothyroidism (SCH) and the response of LVDD to L-thyroxine therapy. This cross-sectional case-control study with one longitudinal arm included 67 patients with SCH attending a tertiary care hospital in Uttarakhand, India, and 67 age- and sex-matched healthy controls. LVDD was assessed by 2D, pulsed-wave Doppler (PWD), continuous wave Doppler (CWD), and tissue Doppler echocardiography (TDE). Patients with LVDD received L-thyroxine therapy with reassessment for LVDD 6 months later. SCH patients had a higher prevalence of LVDD than controls (13.43% versus 1.49%; p = 0.017). LVDD showed a significant association with gender (p = 0.004) and serum FT4 (p = 0.001). E velocity, E' velocity, A' velocity, iso-volumetric relaxation time (IVRT), E/A, and E'/A' ratios were significantly lower, while A velocity, deceleration time (DT), E/E' ratio, left atrial (LA) volume index, and peak tricuspid regurgitation (TR) velocity were significantly higher in cases than controls (p < 0.05 each). The E/A ratio correlated significantly with age, serum very low-density lipoprotein (VLDL), triglycerides (TG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and high-density lipoprotein (HDL) (p < 0.05 each). E' velocity correlated significantly with age, serum total cholesterol, VLDL, and TG (p < 0.05 each), DT with serum total cholesterol (p = 0.047), and LA volume index with age (p = 0.021). Age (p = 0.016) and serum HDL (p = 0.029) were independent predictors of E/A ratio. Gender was an independent predictor for LVDD (p = 0.003). Echocardiographic indices for LVDD showed significant improvement after 6 months of L-thyroxine therapy (p < 0.05 each). LVDD occurs commonly in SCH patients. It can be detected timely using echocardiography and may be reversed by L-thyroxine therapy.

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.

Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

PubMed

Guo, Qingling; Wu, Dan; Yu, Huixin; Bao, Jiandong; Peng, Shiqiao; Shan, Zhongyan; Guan, Haixia; Teng, Weiping

2018-03-01

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth

PubMed Central

Black, Laurel; Bennfors, Grace; Parsons, Trish E.; Elsalanty, Mohammed E.; Yu, Jack C.; Weinberg, Seth M.; Cray, James J.

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology. PMID:27959899

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

PubMed

Howie, R Nicole; Durham, Emily L; Black, Laurel; Bennfors, Grace; Parsons, Trish E; Elsalanty, Mohammed E; Yu, Jack C; Weinberg, Seth M; Cray, James J

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Type 2 diabetes mellitus and hypothyroidism: the possible influence of metformin therapy.

PubMed

Distiller, L A; Polakow, E S; Joffe, B I

2014-02-01

To evaluate the frequency with which hypothyroidism is associated with Type 2 diabetes, to examine gender and ethnic group differences, and to assess the possible impact of metformin therapy. To compare the prevalence of hypothyroidism in a cohort of people with Type 2 diabetes with a previously published cohort of people with Type 1 diabetes from the same centre. We randomly surveyed the records of 922 people with Type 2 diabetes (576 men and 342 women) to identify diagnoses of hypothyroidism, based on current thyroxin replacement therapy (with previous biochemical confirmation). Four subjects had secondary hypothyroidism after radio-iodine therapy for primary hyperthyroidism and were excluded from the analysis. The prevalence of primary hypothyroidism was documented in the remaining 918 subjects. We assessed the association of metformin therapy with hypothyroidism. The overall prevalence of primary hypothyroidism was 11.8% (women: 22.5%; men: 5.4%, P < 0.001) in subjects with Type 2 diabetes. Inter-ethnic differences were noted, with the highest prevalence among white subjects. The prevalence of hypothyroidism was lower in subjects with Type 2 diabetes who were receiving metformin therapy (P < 0.01), and this difference was greater when assessing those who developed primary hypothyroidism after starting metformin therapy (P < 0.001) CONCLUSIONS: Our results support a relatively close association between diabetes and hypothyroidism. Hypothyroidism was more common in the cohort of white subjects than in other ethnic groups. The use of metformin therapy in people with Type 2 diabetes was associated with a significantly lower prevalence of diagnosed hypothyroidism. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Hyperthyroidism in four guinea pigs: clinical manifestations, diagnosis, and treatment.

PubMed

Künzel, F; Hierlmeier, B; Christian, M; Reifinger, M

2013-12-01

Hyperthyroidism was diagnosed in four guinea pigs by demonstration of an increased serum total thyroxine concentration. The main clinical signs were comparable with those observed in feline hyperthyroidism and included weight loss despite maintenance of appetite and a palpable mass in the ventral cervical region. Three animals were treated successfully with methimazole for between 13 and 28 months. Clinical signs and regular measurement of circulating total thyroxine concentrations appear to be convenient parameters for monitoring response to medical therapy. © 2013 British Small Animal Veterinary Association.

Diagnosis and management of subclinical hypothyroidism in pregnancy.

PubMed

Negro, Roberto; Stagnaro-Green, Alex

2014-10-06

In prospective studies, the prevalence of undiagnosed subclinical hypothyroidism in pregnant women ranges from 3% to 15%. Subclinical hypothyroidism is associated with multiple adverse outcomes in the mother and fetus, including spontaneous abortion, pre-eclampsia, gestational hypertension, gestational diabetes, preterm delivery, and decreased IQ in the offspring. Only two prospective studies have evaluated the impact of levothyroxine therapy in pregnant women with subclinical hypothyroidism, and the results were mixed. Subclinical hypothyroidism is defined as raised thyrotropin combined with a normal serum free thyroxine level. The normal range of thyrotropin varies according to geographic region and ethnic background. In the absence of local normative data, the recommended upper limit of thyrotropin in the first trimester of pregnancy is 2.5 mIU/L, and 3.0 mIU/L in the second and third trimester. The thyroid gland needs to produce 50% more thyroid hormone during pregnancy to maintain a euthyroid state. Consequently, most women on levothyroxine therapy before pregnancy require an increase in dose when pregnant to maintain euthyroidism. Ongoing prospective trials that are evaluating the impact of levothyroxine therapy on adverse outcomes in the mother and fetus in women with subclinical hypothyroidism will provide crucial data on the role of thyroid hormone replacement in pregnancy. © BMJ Publishing Group Ltd 2014.

Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

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

Bakhshandeh, Mohsen; Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir; Mahdavi, Seied Rabi Mehdi

Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-basedmore » treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.« less

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism.

PubMed

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine.

Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients.

PubMed

Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

2018-04-01

Thyroid dysfunction during tyrosine kinase inhibitor (TKI) cancer treatment is common, but predisposing risk factors have not been determined. Recommendations for monitoring patients treated with one or multiple TKI and in conjunction with other relevant cancer therapies could be improved. The study objective was to assess the risk factors for new thyroid dysfunction in TKI-treated previously euthyroid cancer patients. A retrospective cohort study of patients with advanced nonthyroidal cancer treated with TKI from 2000 to 2017, having available thyroid function tests showing initial euthyroid status, excluding patients with preexisting thyroid disease or lack of follow-up thyroid function tests. During TKI treatment, patients were classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (TSH >10 mIU/L, low free thyroxine, or requiring thyroid hormone replacement). The timing of thyroid dysfunction and TKI used were assessed. Risk factors for incident hypothyroidism were evaluated using multivariate models. In 538 adult patients included, subclinical hypothyroidism occurred in 71 (13.2%) and overt hypothyroidism occurred in 144 (26.8%) patients with TKI therapy, following a median cumulative TKI exposure of 196 days (interquartile range [IQR] 63.5-518.5 days). The odds of hypothyroidism were greatest during the first six months on a TKI. Median exposure time on the TKI concurrent with thyroid dysfunction in patients treated with only one TKI was 85 days (IQR 38-293.5 days) and was similar to the 74 days (IQR 38-133.3 days) in patients treated previously with other TKI (p = 0.41). Patients who developed hypothyroidism compared to those who remained euthyroid had greater odds of being female (odds ratio = 1.99 [confidence interval 1.35-2.93], p < 0.01), but greater cumulative TKI exposure and greater number of TKI received were not associated with thyroid dysfunction. Thyroid dysfunction occurred in 40% of euthyroid patients. Monitoring thyroid function in TKI-treated patients is recommended, with particular attention to female patients and within the first six months of exposure to a new TKI.

Management of hyperthyroidism during pregnancy and lactation.

PubMed

Azizi, Fereidoun; Amouzegar, Atieh

2011-06-01

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.' Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

PubMed

Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

2017-09-22

Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

Adjunctive cholestyramine therapy for thyrotoxicosis.

PubMed

Solomon, B L; Wartofsky, L; Burman, K D

1993-01-01

Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone. A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one-week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day. Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study. Total and free thyroxine and triiodothyronine, as well as thyroid-stimulating immunoglobulin and thyrotrophin-binding inhibitory immunoglobulin, were measured weekly. Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine-treated group (F = 4-7, P < 0.01) than in the placebo group (F = 2-3.1, P = 0.05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time. We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment.

Simulation of Post-Thyroidectomy Treatment Alternatives for Triiodothyronine or Thyroxine Replacement in Pediatric Thyroid Cancer Patients

PubMed Central

Ben-Shachar, Rotem; Huang, Stephen A.; DiStefano, Joseph J.

2012-01-01

Background As in adults, thyroidectomy in pediatric patients with differentiated thyroid cancer is often followed by 131I remnant ablation. A standard protocol is to give normalizing oral thyroxine (T4) or triiodothyronine (T3) after surgery and then withdraw it for 2 to 6 weeks. Thyroid remnants or metastases are treated most effectively when serum thyrotropin (TSH) is high, but prolonged withdrawals should be avoided to minimize hypothyroid morbidity. Methods A published feedback control system model of adult human thyroid hormone regulation was modified for children using pediatric T4 kinetic data. The child model was developed from data for patients ranging from 3 to 9 years old. We simulated a range of T4 and T3 replacement protocols for children, exploring alternative regimens for minimizing the withdrawal period, while maintaining normal or suppressed TSH during replacement. The results are presented with the intent of providing a quantitative basis to guide further studies of pediatric treatment options. Replacement was simulated for up to 3 weeks post-thyroidectomy, followed by various withdrawal periods. T4 vs. T3 replacement, remnant size, dose size, and dose frequency were tested for effects on the time for TSH to reach 25 mU/L (withdrawal period). Results For both T3 and T4 replacement, higher doses were associated with longer withdrawal periods. T3 replacement yielded shorter withdrawal periods than T4 replacement (up to 3.5 days versus 7–10 days). Higher than normal serum T3 concentrations were required to normalize or suppress TSH during T3 monotherapy, but not T4 monotherapy. Larger remnant sizes resulted in longer withdrawal periods if T4 replacement was used, but had little effect for T3 replacement. Conclusions T3 replacement yielded withdrawal periods about half those for T4 replacement. Higher than normal hormone levels under T3 monotherapy can be partially alleviated by more frequent, smaller doses (e.g., twice a day). LT4 may be the preferred option for most children, given the convenience of single daily dosing and familiarity of pediatric endocrinologists with its administration. Remnant effects on withdrawal period highlight the importance of minimizing remnant size. PMID:22578300

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM.

PubMed

Hennessey, James V

2015-10-01

To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies. A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature. A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products. The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism

PubMed Central

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine. PMID:28971179

Effects of thyroxin therapy on different analytes related to obesity and inflammation in dogs with hypothyroidism.

PubMed

Tvarijonaviciute, A; Jaillardon, L; Cerón, J J; Siliart, B

2013-04-01

Hypothyroidism in dogs is accompanied by changes in intermediary metabolism including alterations in bodyweight (BW), insulin resistance, and lipid profile. In this study, changes in selected adipokines (adiponectin, leptin), butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with hypothyroidism under thyroxin therapy. Blood samples were collected when hypothyroidism was diagnosed (before treatment) and after treatment with thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group A), whereas the remainder were considered to have been insufficiently treated (group B). Following treatment, group A dogs demonstrated a statistically significant decrease in canine thyroid stimulating hormone (c-TSH) (P<0.001) and an increase in free thyroxine (fT4) (P<0.001) concentrations, associated with a significant decrease in BW (P<0.05), leptin (P<0.01), and adiponectin, (P<0.001) and an increase in BChE (P<0.01) and Hp (P<0.05). Group B dogs showed no statistically significant changes in c-TSH, but had a significant increase in fT4 (P<0.001) accompanied by a significant decrease in adiponectin (P<0.05) of lower magnitude than group A. No significant changes in the mean circulating levels of APPs were observed in both groups, with the exception of an increase in Hp (P<0.05) in group A. In summary, the successful treatment of hypothyroidism reduces circulating levels of adiponectin and leptin, while increasing BChE activity in dogs. The mean increase in Hp values and decrease in SAA for some of the dogs after treatment warrants further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmaceutical studies of levothyroxine sodium hydrate suppository provided as a hospital preparation.

PubMed

Hamada, Yuhei; Masuda, Kazushi; Okubo, Masato; Nakasa, Hiromitsu; Sekine, Yuko; Ishii, Itsuko

2015-01-01

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital's protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4 °C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.

Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

PubMed

Schenke, S; Klett, R; Braun, S; Zimny, M

2013-01-01

Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

Hypothyrodism in male patients: a descriptive, observational and cross-sectional study in a series of 260 men.

PubMed

Iglesias, Pedro; Díez, Juan J

2008-10-01

Several aspects of thyroid dysfunction have not been fully characterized in large series of male patients. Our aim was to investigate the etiology and clinical features of hypothyroidism and assess the adequacy of replacement therapy in men attending an endocrinology clinic. We studied a group of 260 men (mean (+/-standard deviation) age 58.3 +/- 16.1 years) periodically seen because of thyroid hypofunction. We evaluated the etiology of hypothyroidism, presence or absence of goiter, time of evolution from diagnosis, current thyroid autoimmunity and thyroid functional status, and adequacy of disease control. Overt hypothyroidism was found in 182 (70.0%) and subclinical hypothyroidism in 78 (30.0%) patients. Autoimmune thyroiditis was the most frequent etiology (n = 107, 41.2%). Of these, 96 (89.7%) showed no goiter. Thyroid peroxidase antibodies were measured in 238 patients, being positive in 129 (54.2%) and negative in 109 (45.8%) patients. After excluding patients with thyroid carcinoma and those with recently diagnosed hypothyroidism, we found an adequate control of thyroid function, ie, normal thyrotropin and free thyroxine levels, in 95 patients (64.2%). Adequacy of treatment did not show any relationship with age, age at diagnosis, etiology, and autoimmune status. However, adequacy was significantly related to the degree of thyroid hypofunction (P < 0.001) and to the duration of disease (P < 0.01). We conclude that autoimmune thyroiditis, mainly the nongoitrous form, and postoperative hypothyroidism are the foremost causes of thyroid hypofunction in male patients. Adequacy of replacement treatment seems to be mainly related to the degree of thyroid hypofunction and the time from starting therapy.

Asymptomatic myotonia congenita unmasked by severe hypothyroidism.

PubMed

Passeri, Elena; Sansone, Valeria A; Verdelli, Chiara; Mendola, Marco; Corbetta, Sabrina

2014-04-01

Myotonia congenita is an inherited muscle disorder sustained by mutations in the skeletal muscle chloride channel gene CLCN1. Symptoms vary from mild to severe and generalized myotonia and worsen with cold, stressful events and hormonal fluctuations. Here we report the case of a young woman who sought medical attention because of subacute onset of diffuse and severe limb myotonia. CLCN1 gene sequencing showed a heterozygous transversion (T550M), two polymorphisms and one silent mutation. Thyroid function screening revealed severe hypothyroidism. She was placed on l-thyroxine replacement therapy which dramatically improved myotonia. We conclude that hypothyroidism unmasked a genetically determined, clinically asymptomatic chloride channelopathy. Diagnostic work-up in patients with clinically isolated myotonia should not be limited to genetic screening of non-dystrophic or dystrophic myotonias. Considering the high prevalence of hypothyroidism in females, systematic thyroid function screening by looking for additional hypothyroid symptoms and serum TSH levels measurement is mandatory in these patients. Copyright © 2014 Elsevier B.V. All rights reserved.

RADIOACTIVE IODINE THERAPY WITHOUT RECENT ANTITHYROID DRUG PRETREATMENT FOR HYPERTHYROIDISM COMPLICATED BY SEVERE HYPERBILIRUBINEMIA DUE TO HEPATIC DYSFUNCTION: EXPERIENCE OF A CHINESE MEDICAL CENTER.

PubMed

Ding, Yong; Xing, Jialiu; Qiu, Zewu; Wang, Yong; Zhang, Youren; Fang, Yi; Peng, Xiaobo; Long, Yahong; Deng, Pei

2016-02-01

The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction. Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy. After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy. (131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

PubMed

Maruo, Yoshihiro; Mori, Asami; Morioka, Yoriko; Sawai, Chihiro; Mimura, Yu; Matui, Katsuyuki; Takeuchi, Yoshihiro

2016-01-12

Resistance to thyroid hormone beta (RTHβ) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor β gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone. The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis. In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

Atrial fibrillation associated with exogenous subclinical hyperthyroidism.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-11-19

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Moreover acute myocardial infarction has been reported during L-thyroxine substitution therapy. Far more common and relatively less studied is exogenous subclinical hyperthyroidism caused by L-thyroxine administration to thyroidectomized or hypothyroid patients or patients with simple or nodular goiter. We present a case of atrial fibrillation associated with exogenous subclinical hyperthyroidism, in a 72-year-old Italian woman. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

PubMed

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

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

Meric, S.M.; Hawkins, E.C.; Washabau, R.J.

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after /sup 131/I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before /sup 131/I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidlymore » during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.« less

THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.

PubMed

Seo, Changhwan; Kim, Seonghun; Lee, Misol; Cha, Min-Uk; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jhee, Jong Hyun; Kee, Youn Kyung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook; Park, Jung Tak

2018-03-01

Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.

Hypoplastic anaemia complicating myxoedema coma.

PubMed

Song, S H; McCallum, C J; Campbell, I W

1998-10-01

The case of a 68 year old women presenting in myxoedema coma is described. She was found to be anaemic with a haemoglobin of 8.2 g/dl. Further investigations showed a pancytopenia and a hypoplastic anaemia confirmed by bone marrow. The patient recovered and became euthyroid following initial treatment with intravenous tri-iodothyronine (T3) and later oral thyroxine (T4) replacement with resolution of pancytopenia and return of bone marrow to normal.

Comparative evaluation of therapy with L-thyroxine versus no treatment in children with idiopathic and mild subclinical hypothyroidism.

PubMed

Wasniewska, Malgorzata; Corrias, Andrea; Aversa, Tommaso; Valenzise, Mariella; Mussa, Alessandro; De Martino, Lucia; Lombardo, Fortunato; De Luca, Filippo; Salerno, Mariacarolina

2012-01-01

The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T(4)) versus those receiving no therapy. (a) To evaluate thyroid tests under L-T(4) and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Group A children were treated for 24 months and TSH and FT(4) levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH. Copyright © 2012 S. Karger AG, Basel.

Hypothyroidism and its rapid correction alter cardiac remodeling.

PubMed

Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

2014-01-01

The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling

PubMed Central

Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

2014-01-01

The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease. PMID:25333636

A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

PubMed

Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

2007-01-01

To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study.

PubMed

Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung

2016-02-01

The aim of this study was to evaluate the risk of depression in and effect of L-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18-2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66-1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression.

Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan

PubMed Central

Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung

2016-01-01

Abstract The aim of this study was to evaluate the risk of depression in and effect of l-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan. In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort. In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18–2.13). The risk of depression decreased after administration of l-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66–1.59). In Taiwan, the overall incidence of depression was greater in the young HT cohort. l-thyroxine treatment reduced the risk of depression. PMID:26871858

Effect of thyroxine supplementation on glomerular filtration rate in hypothyroid dogs.

PubMed

Gommeren, K; van Hoek, I; Lefebvre, H P; Benchekroun, G; Smets, P; Daminet, S

2009-01-01

Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking. Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism. Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis. Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n=14) and at 1 month (T1, n=14) and at 6 months (T6, n=11) after beginning levothyroxine supplementation therapy (20 microg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean+/-standard deviation. At T0, the average age of dogs in the study group was 6.3+/-1.4 years. Their average body weight decreased from 35+/-18 kg at T0 to 27+/-14 kg at T6 (P<.05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6+/-0.4 mL/min/kg at T0, 2.1+/-0.4 at T1, and 2.0+/-0.4 at T6 (P<.01). GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.

No impact of dietary iodine restriction in short term development of hypothyroidism following fixed dose radioactive iodine therapy for Graves' disease.

PubMed

Jacob, Jubbin Jagan; Stephen, Charles; Paul, Thomas V; Thomas, Nihal; Oommen, Regi; Seshadri, Mandalam S

2015-01-01

The increased incidence of autoimmune thyroid disease with increasing dietary iodine intake has been demonstrated both epidemiologically and experimentally. The hypothyroidism that occurs in the first year following radioactive iodine therapy is probably related to the destructive effects of the radiation and underlying ongoing autoimmunity. To study the outcomes at the end of six months after fixed dose I, (131)therapy for Graves' disease followed by an iodine restricted diet for a period of six months. Consecutive adult patients with Graves' disease planned for I(131) therapy were randomized either to receive instructions regarding dietary iodine restriction or no advice prior to fixed dose (5mCi) I(131) administration. Thyroid functions and urinary iodine indices were evaluated at 3(rd) and 6(th) month subsequently. Forty seven patients (13M and 34F) were assessed, 2 were excluded, 45 were randomized (Cases 24 and Controls 21) and 39 patients completed the study. Baseline data was comparable. Median urinary iodine concentration was 115 and 273 μg/gm creat (p = 0.00) among cases and controls respectively. Outcomes at the 3(rd) month were as follows (cases and controls); Euthyroid (10 and 6: P = 0.24), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 8: P = 0.64). Outcomes at the end of six months were as follows (cases and controls); Euthyroid (10 and 5: P = 0.12), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 9: P = 0.43). Of the hypothyroid patients 5 (cases 1 and controls 4: P = 0.13) required thyroxine replacement. There was no statistical significant difference in the outcome of patients with dietary iodine restriction following I(131) therapy for Graves' disease.

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

[Prevention of recurrent amiodarone-induced hyperthyroidism by iodine-131].

PubMed

Hermida, J S; Jarry, G; Tcheng, E; Moullart, V; Arlot, S; Rey, J L; Schvartz, C

2004-03-01

Amioradone-induced hyperthyroidism is a common complication of amiodarone therapy. Although definitive interruption of amiodarone is recommended because of the risks of aggravation of the arrhythmias, some patients may require the reintroduction of amiodarone several months after normalisation of thyroid function. The authors undertook a retrospective study of the effects of preventive treatment of recurrences of amiodarone-induced hyperthyroidism with I131. The indication of amiodarone therapy was recurrent, symptomatic, paroxysmal atrial fibrillation in 13 cases and ventricular tachycardia in 5 cases (M = 14, average age 64 +/- 13 years). The underlying cardiac disease was dilated cardiomyopathy (N = 5), ischaemic heart disease (N = 3), hypertensive heart disease (N = 2), arrhythmogenic right ventricular dysplasia (N = 2) or valvular heart disease (N = 2). Two patients had idiopathic atrial fibrillation. An average dose of 576 +/- 184 MBq of I131 was administered 34 +/- 37 months after an episode of amiodarone-induced hyperthyroidism. Amiodarone was reintroduced in 16 of the 18 patients after a treatment-free period of 98 +/- 262 days. Transient post-radioiodine hyperthyroidism was observed in 3 cases (17%). Sixteen patients (89%) developed hypothyroidism requiring replacement therapy with L-thyroxine. There were no recurrences of amiodarone-induced hyperthyroidism. After 24 +/- 17 months follow-up, the arrhythmias were controlled in 13 of the 16 patients (81%) who underwent the whole treatment sequence. The authors conclude that preventive treatment with I131 is an effective alternative to prevent recurrence of amiodarone-induced hyperthyroidism in patients requiring reintroduction of amiodarone to control their arrhythmias.

Adult-onset demodicosis in two dogs due to Demodex canis and a short-tailed demodectic mite.

PubMed

Saridomichelakis, M; Koutinas, A; Papadogiannakis, E; Papazachariadou, M; Liapi, M; Trakas, D

1999-11-01

Infestation with a short-tailed demodectic mite and Demodex canis was diagnosed in both a six-and-a-half-year-old and a four-year-old dog. The clinical picture was compatible with generalised demodicosis complicated by staphylococcal pyoderma (case 1), or localised demodicosis (case 2). In both cases, the short-tailed demodectic mite outnumbered D canis in superficial skin scrapings. The laboratory findings (lymphopenia, eosinopenia, increased serum alkaline phosphatase and alanine aminotransferase activities, diluted urine and proteinuria) and the results of a low dose dexamethasone suppression test were suggestive of underlying hyperadrenocorticism in the first case. Hypothyroidism was considered a possibility in the second case, owing to the sustained bradycardia and the extremely low basal total thyroxine value. Systemic treatment with ivermectin and cephalexin (case 1), or topical application of an amitraz solution in mineral oil, along with sodium levothyroxine replacement therapy (case 2), resulted in a complete resolution of the skin lesions and the disappearance of both types of demodectic mite after two and one and a half months, respectively.

Clinical, behavioural and pharmacogenomic factors influencing the response to levothyroxine therapy in patients with primary hypothyroidism-protocol for a systematic review.

PubMed

Dew, Rosie; Okosieme, Onyebuchi; Dayan, Colin; Eligar, Vinay; Khan, Ishrat; Razvi, Salman; Pearce, Simon; Wilkes, Scott

2017-03-21

Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism. The databases Web of Science, Cochrane Library, EMBASE and PubMed will be searched. Patients must be adults over the age of 18 years, suffering from primary hypothyroidism including overt and subclinical hypothyroidism and receiving levothyroxine treatment. Studies in children, pregnant women and patients with secondary or tertiary hypothyroidism will not be included. We will also exclude studies focused on forms of thyroid hormone replacement therapy other than levothyroxine. The primary outcome is to quantify the effect of clinical, behavioural and pharmacogenomic factors on thyroid stimulating hormone (TSH) levels. Secondary outcomes are the effect these factors have on thyroxine (T4) and triiodothyronine (T3) levels, mortality, morbidity, quality of life, treatment complications, adverse effects, physical and social functioning. Studies will be screened through reading the title, abstract and then full text. Two reviewers will independently extract the data and select articles, and a third reviewer will be consulted if there is any disagreement. We will undertake a meta-analysis of studies in which there is a defined intervention or exposure, patients are receiving levothyroxine for hypothyroidism, there is an appropriate control group of levothyroxine treated patients that are not exposed to the intervention, and the primary outcome is determined by serum TSH levels. Studies will comprise of randomised controlled trials as well as observational data. Eligible studies will be assessed for bias using the risk of bias tool available in the Cochrane handbook 2011, and the quality of evidence will be judged according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A flow diagram describing the data search will be created according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis: The PRISMA statement. A narrative synthesis will be undertaken in the description of the data, and summary tables will be created of the results. This review will be the first systematic review of this nature. The evidence synthesised will be useful to general practitioners in their management of hypothyroidism. Findings will be disseminated at conferences and in professional and peer-reviewed journals. PROSPERO CRD42015027211.

Hypothyroidism and Nephrotic Syndrome: Why, When and How to Treat.

PubMed

Mario, F Di; Pofi, R; Gigante, A; Rivoli, L; Rosato, E; Isidori, A M; Cianci, R; Barbano, B

2017-01-01

Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free triiodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine- binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition. In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacotherapy for thyroid nodules. A systematic review and meta-analysis.

PubMed

Richter, Bernd; Neises, Gudrun; Clar, Christine

2002-09-01

The review highlights the uncertainty in the management of nodular thyroid disease. Thyroxine suppressive treatment is given in the hope that nodules might decrease in size, sometimes assuming that dependency on TSH is different in benign and malignant nodular disease. Follow-up of benign nodules over 10 years suggested that most remain the same, shrink, or disappear [14]. TSH suppression may lead to hyperthyroidism, reduced bone density [37.39], and atrial fibrilation; however, apart from reduction of nodule size or arrest in nodule growth, thyroxine therapy may benefit patients by reducing perinodular volume. Consequently, both pressure symptoms and cosmetic complaints could improve. Unfortunately, no information concerning symptoms or well-being is available from published randomized trials. In conclusion, more high quality studies of sufficient duration with adequate power estimation are needed. Uncertainty about predictors of response or the impact on outcomes that are important to patients leaves considerable doubt about the wisdom of applying suppressive therapy. Future studies shoudl include patient-important outcomes including thyroid cancer incidence, health-related quality of life and costs.

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.

Follow-up of differentiated thyroid carcinoma.

PubMed

Pagano, L; Klain, M; Pulcrano, M; Angellotti, G; Pasano, F; Salvatore, M; Lombardi, G; Biondi, B

2004-12-01

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Hypopituitarism.

PubMed

Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

2016-11-12

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Myxedema coma.

PubMed

Kwaku, Maxwell P; Burman, Kenneth D

2007-01-01

Untreated or unrecognized hypothyroidism may progress to severe decompensated hypothyroidism or myxedema coma. Relatively few cases are reported in the literature since the first case was apparently reported from the St. Thomas Hospital in London in 1879. The paucity of cases may be due to either underreporting or improvement in the diagnosis and treatment of uncomplicated hypothyroidism. However, despite the ready availability of sensitive thyrotropin assays, the recognition and treatment of myxedema coma remains a challenge. Although thyroid hormone treatment is highly effective when combined with ventilatory and hemodynamic support in the intensive care unit setting, controversies abound on the optimal and most effective choice of thyroid hormone preparation: thyroxine and triiodothyronine and in what amount. Accumulated evidence now shows that proper use of either thyroxine alone or in combination with triiodothyronine may be effective therapy.

[Radioiodine 131I therapy of hyperthyroidism on an outpatient basis - safe, effective and economic option].

PubMed

Jiskra, J; Kubinyi, J; Telička, Z

2012-02-01

Radioiodine 131I therapy of hyperthyroidism on an outpatient basis is widely accepted over the world. In Czech Republic, however, radioiodine therapy is still not enough used, and has been realized on an inpatient basis to date. Our work is the first analysis of the experiences with radioiodine therapy of hyperthyroidism on an outpatient basis in Czech Republic. Capsule with 550 MBq of 131I was administered orally in 39 hyperthyroid patients (32 women and 8 men, 21 with autoimmune Graves hyperthyroidism and 18 with toxic thyroid nodules, mean age 66.8 years). In 32 of them we evaluated effectiveness and complications of therapy after 12-42 months. We also compared financial costs of the radioiodine treatment on an outpatient basis with the treatment in hospitalization and with surgery. After the treatment, 9/32 (28 %) patients were euthyroid without thyrostatic/thyroxine treatment, 18/32 (60 %) patients were hypothyroid with thyroxine therapy, 2/32 (6 %) patients significantly decreased doses of thyrostatic drugs. In 2/32 (6 %) patients the treatment was ineffective. The effect of the treatment did not depend on the etiology and severity of hyperthyroidism, but decreased with thyroid volume. Patients with ineffective or only partially effective treatment had median of thyroid volume more than 40 ml. In 1 patient thyroid associated ophthalmopathy was moderately worsened. Other complications were not observed. If we compared financial costs in model with 1 patient, we found that the costs of radioiodine therapy on an outpatient basis (118.7 €) comprise only 16 % of the costs of radioiodine therapy in hospitalization (728 €) and only 25 % of the costs of surgery (475.6 €). Radioiodine 131I is effective and safe in the treatment of hyperthyroidism and the therapy on an outpatient basis is much cheaper choice. The therapy with 131I on an outpatient basis is not suitable in patients with thyroid volume more than 40 ml.

RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDS, PCDFS AND PCBS

EPA Science Inventory

RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDs, PCDFs AND PCBs. D G Ross, K M Crofton, M J DeVito, NHEERL, ORD, USEPA, RTP, NC.
Many PHAHs decrease thyroxine (T4), possibly due to inducti...

Improving efficacy of the adjustable gastric band: studies of the use of adjuvant approaches in a rodent model.

PubMed

Stefanidis, Aneta; Man Lee, Christine Cheuk; Brown, Wendy A; Oldfield, Brian J

2017-02-01

The laparoscopic adjustable gastric band (AGB) has been effective in reducing excess weight by approximately 50% for at least 16 years. However, as with all weight loss approaches, reduction in weight resulting from bariatric surgery is associated with a compensatory reduction in energy expenditure, which may confound and limit weight loss. Adjuvant therapies that reduce food intake and increase energy expenditure may be used to improve weight loss outcomes by ameliorating, or even reversing, this reduction in energy expenditure. Rats were either fitted with an AGB or were sham operated and received one of 2 adjunctive pharmacologic treatments, (1) thyroxine or (2) bupropion/naltrexone (Contrave), at a range of doses and matched with vehicle controls (n = 6-8/group) over a 4-week period of combined treatments. Metabolic parameters including food intake, weight, fat mass, and energy expenditure in brown adipose tissue (BAT), whole body calorimetry, and physical activity were assessed. Inflation of the AGB caused a reduction in weight gain that was further enhanced by cotreatment with either thyroxine or Contrave (P<.05). Thyroxine completely ameliorated the reduction in AGB-induced BAT thermogenesis and significantly improved weight loss, particularly in fat mass. Contrave also augmented the loss of weight and fat mass associated with the AGB and increased BAT thermogenesis in banded rats even at doses below that required to change food intake. Adjuvant therapies can improve the efficacy of the AGB, at least in part by negating the compensatory reduction in energy expenditure, but also via a combined effect on food intake. Copyright © 2017 American Society for Bariatric Surgery. All rights reserved.

Five-Year Follow-Up for Women With Subclinical Hypothyroidism in Pregnancy

PubMed Central

Shields, Beverley M.; Knight, Bridget A.; Hill, Anita V.; Hattersley, Andrew T.

2013-01-01

Context: Increasing numbers of women are being treated with l-thyroxine in pregnancy for mild thyroid dysfunction because of its association with impaired neuropsychological development in their offspring and other adverse obstetric outcomes. However, there are limited data to indicate whether treatment should be continued outside of pregnancy. Objectives: We aimed to determine whether subclinical hypothyroidism and maternal hypothyroxinemia resolve postdelivery. Design, Setting, and Participants: A total of 523 pregnant healthy women with no known thyroid disorders were recruited during routine antenatal care and provided blood samples at 28 weeks of pregnancy and at a mean of 4.9 years postpregnancy. Main Outcome Measures: TSH, free T4, free T3, and thyroid peroxidase antibody levels were measured in serum taken in pregnancy and at follow-up. Results: Subclinical hypothyroidism in pregnancy (TSH >3 mIU/L) was present in 65 of 523 (12.4%) women. Of these, 49 (75.4%) women had normal thyroid function postpregnancy; 16 of 65 (24.6%) had persistent high TSH (TSH >4.5 mIU/L postpregnancy) with 3 women receiving l-thyroxine treatment. A total of 44 of 523 (8.4%) women had isolated maternal hypothyroxinemia in pregnancy (free T4 <10th centile and TSH ≤3 mIU/L). Only 2 of 44 (4.5%) had TSH >4.5 mIU/L outside pregnancy. Of the women with subclinical hypothyroidism in pregnancy with antibody measurements available, those with thyroid peroxidase antibodies in pregnancy were more likely to have persistently elevated TSH or be receiving l-thyroxine replacement after pregnancy (6 of 7 [86%] vs 10 of 57 [18%], P < .001). Conclusions: The majority of cases of subclinical hypothyroidism in pregnancy are transient, so treatment with l-thyroxine in these patients should be reviewed because it may not be warranted after pregnancy. PMID:24217906

Diagnosis of hyperthyroidism in cats with mild chronic kidney disease.

PubMed

Wakeling, J; Moore, K; Elliott, J; Syme, H

2008-06-01

In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.

Congenital Type III von Willebrand's disease unmasked by hypothyroidism in a Shetland sheepdog.

PubMed

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-09-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand's disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog's sudden bleeding tendency as has been seen with hypothyroidism in humans.

Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

PubMed Central

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-01-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans. PMID:26347307

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

21 CFR 862.1695 - Free thyroxine test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may...

Menopausal Symptom Relief and Side Effects Experienced by Women Using Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 1.

PubMed

Deleruyelle, Laura J

2016-01-01

The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t -test, two-sample t -test, and f tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. The results of this study will be summarized in forthcoming articles in this series. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Estimation of Rapidly Exchangeable Cellular Thyroxine from the Plasma Disappearance Curves of Simultaneously Administered Thyroxine-131I and Albumin-125I*

PubMed Central

Oppenheimer, Jack H.; Bernstein, Gerald; Hasen, Julian

1967-01-01

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-131I and albumin-125I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-125I can be used to represent the expansion of the thyroxine-131I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-131I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-131I and albumin-125I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-131I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation. PMID:4960936

Hypopituitarism in a patient with Beckwith-Wiedemann syndrome due to hypomethylation of KvDMR1.

PubMed

Baiocchi, Michela; Yousuf, Fatimah Sireen; Hussain, Khalid

2014-04-01

Beckwith-Wiedemann syndrome (BWS) is caused by dysregulation of imprinted genes on chromosome 11.p15.5. The syndrome includes overgrowth, macroglossia, organomegaly, abdominal wall defects, hypoglycemia, and long-term malignancy risk. No patient who has BWS has been reported with hypopituitarism. We describe a patient who presented at birth with macrosomia, macroglossia, respiratory distress, jaundice, and hypoglycemia, and who was followed for 4.5 years. Genetic test for BWS was performed, which detected loss of maternal methylation on region KvDMR1 (11p15.5). The hypoglycemia was attributable to hyperinsulinism and was treated with diazoxide and chlorothiazide. She responded well, but the hypoglycemia returned after reducing the diazoxide. It was possible to stop the diazoxide after 2.5 years. On routine follow-up she was noted to be developing short stature. Baseline pituitary and growth hormone (GH) stimulation tests detected GH deficiency and secondary hypothyroidism. A brain MRI showed a small anterior pituitary gland. Thereafter, thyroxine and replacement therapy with GH were started, which resulted in a remarkable improvement in growth velocity. This is the first patient to be reported as having hypopituitarism and BWS. It is unclear if the BWS and the hypopituitarism are somehow connected; however, further investigations are necessary. Hypopituitarism explains the protracted hypoglycemia and the short stature. In our patient, GH therapy seems to be safe, but strict follow-up is required given the increased cancer risk related to BWS.

[Myxedema coma as a rare differential diagnosis of severe consciousness disturbance].

PubMed

Kollmar, R; Schellinger, P D; Bardutzky, J; Meisel, F; Schwaninger, M

2002-12-01

Myxedema coma is a rare and life-threatening complication of untreated hypothyroidism. Therefore, it must be part of the differential diagnosis in comatose patients. We report one patient who presented with CO(2) narcosis,hypothermia, bradycardia,hyporeflexia, tetraparesis, ascitis, pleural effusions, and heart insufficiency. Examination of the CSF, cranial CT, MRI, and MR angiography were normal. In suspicion of myxedema coma,the patient was treated with high dose L-thyroxine and hydrocortisone for preventing secondary adrenal insufficiency. A fast clinical recovery, decreased T4 (7.2 ng/l) and T3 (0.93 ng/l), and increased TSH (20.19 mU/l) together with the following anamnesis of radio iodine therapy and insufficient thyroxine intake confirmed the diagnosis. In conclusion, treatment of the myxedema coma must be started as soon as the laboratory results are confirmatory, since its course depends on the time of initiation of treatment.

The effects of thyroxine on metabolism and water balance in a desert-dwelling rodent, Merriam's kangaroo rat (Dipodomys merriami).

PubMed

Banta, Marilyn R; Holcombe, Dale W

2002-01-01

Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need to conserve both energy and water to survive desert conditions characterized by aridity and low productivity. The thyroid hormone thyroxine increases both basal metabolic rate and urinary water loss in mammals. Increases in basal metabolism and urinary water loss are likely to be detrimental to D. merriami, therefore the regulation of this hormone may be important. To examine the effects of thyroxine in this species, we implanted adult kangaroo rats with pellets designed to release specific doses of thyroxine at a constant rate for 90 days or a placebo pellet. We measured plasma thyroxine concentration, basal metabolic rate, food consumption, urine concentration and water loss in all implanted animals. Thyroxine implants significantly increased both plasma thyroxine and basal metabolic rate in a relatively dose-dependent manner. In response to thyroxine. kangaroo rats increased food consumption only slightly, but this small increase was sufficient to compensate for their elevated metabolic rates. Neither urine concentration nor water loss varied among treatment groups. Thyroxine increased energy expenditure but not water loss in this species.

Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 2.

PubMed

Deleruyelle, Laura J

2016-01-01

The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provides a brief discussion on the significance of this study to nursing and provides the methods used in this study. The results of this study will be summarized in forthcoming articles in this series. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.

PubMed

Deleruyelle, Laura J

2017-01-01

The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion on the significance of this study to nursing and provided the methods used in this study. The results and conclusion of this study are provided within this article. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Specific labeling of the thyroxine binding site in thyroxine-binding globulin: determination of the amino acid composition of a labeled peptide fragment isolated from a proteolytic digest of the derivatized protein.

PubMed

Tabachnick, M; Perret, V

1987-08-01

[125I] Thyroxine has been covalently bound to the thyroxine binding site in thyroxine-binding globulin by reaction with the bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. An average of 0.47 mol of [125I] thyroxine was incorporated per mol protein; nonspecific binding amounted to 8%. A labeled peptide fragment was isolated from a proteolytic digest of the derivatized protein by HPLC and its amino acid composition was determined. Comparison with the amino acid sequence of thyroxine-binding globulin indicated partial correspondence of the labeled peptide with two possible regions in the protein. These regions also coincide with part of the barrel structure present in the closely homologous protein, alpha 1-antitrypsin.

Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition.

PubMed

Alvarez-Escolá, Cristina; Fernández-Rodríguez, Eva; Recio-Córdova, José María; Bernabéu-Morón, Ignacio; Fajardo-Montañana, Carmen

2014-02-01

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height). The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Thyroid disorders associated with pregnancy: etiology, diagnosis, and management.

PubMed

Lazarus, John H

2005-01-01

Pregnancy has an effect on thyroid economy with significant changes in iodine metabolism, serum thyroid binding proteins, and the development of maternal goiter especially in iodine-deficient areas. Pregnancy is also accompanied by immunologic changes, mainly characterized by a shift from a T helper-1 (Th1) lymphocyte to a Th2 lymphocyte state. Thyroid peroxidase antibodies are present in 10% of women at 14 weeks' gestation, and are associated with (i) an increased pregnancy failure (i.e. abortion), (ii) an increased incidence of gestational thyroid dysfunction, and (iii) a predisposition to postpartum thyroiditis. Thyroid function should be measured in women with severe hyperemesis gravidarum but not in every patient with nausea and vomiting during pregnancy. Graves hyperthyroidism during pregnancy is best managed with propylthiouracil administered throughout gestation. Thyroid-stimulating hormone-receptor antibody measurements at 36 weeks' gestation are predictive of transient neonatal hyperthyroidism, and should be checked even in previously treated patients receiving thyroxine. Postpartum exacerbation of hyperthyroidism is common, and should be evaluated in women with Graves disease not on treatment. Radioiodine therapy in pregnancy is absolutely contraindicated. Hypothyroidism (including subclinical hypothyroidism) occurs in about 2.5% of pregnancies, and may lead to obstetric and neonatal complications as well as being a cause of infertility. During the last few decades, evidence has been presented to underpin the critical importance of adequate fetal thyroid hormone levels in order to ensure normal central and peripheral nervous system maturation. In iodine-deficient and iodine-sufficient areas, low maternal circulating thyroxine levels have been associated with a significant decrement in child IQ and development. These data suggest the advisability of further evaluation for a screening program early in pregnancy to identify women with hypothyroxinemia, and the initiation of prompt treatment for its correction. Hypothyroidism in pregnancy is treated with a larger dose of thyroxine than in the nonpregnant state. Postpartum thyroid dysfunction (PPTD) occurs in 50% of women found to have thyroid peroxidase antibodies in early pregnancy. The hypothyroid phase of PPTD is symptomatic and requires thyroxine therapy. A high incidence (25-30%) of permanent hypothyroidism has been noted in these women. Women having transient PPTD with hypothyroidism should be monitored frequently, as there is a 50% chance of these patients developing hypothyroidism during the next 7 years.

Plasma thyroxine changes of the Apollo crewmen

NASA Technical Reports Server (NTRS)

Sheinfeld, M.; Leach, C. S.; Johnson, P. C.

1975-01-01

Blood drawn from Apollo crew members prior to the mission, at recovery, and postmission, was used to examine the effect Apollo mission activities have on thyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that Apollo activities and environment caused the postmission increase in plasma thyroxine. The prolonged postmission decreases in serum cholesterol may be one result of the increased thyroxine activity.

Risk of hypothyroidism among patients with nasopharyngeal carcinoma treated with radiation therapy: A Population-Based Cohort Study.

PubMed

Fan, Chao-Yueh; Lin, Chun-Shu; Chao, Hsing-Lung; Huang, Wen-Yen; Su, Yu-Fu; Lin, Kuen-Tze; Tsai, I-Ju; Kao, Chia-Hung

2017-06-01

This study aimed to assess the incidence and risk of hypothyroidism among patients with nasopharyngeal carcinoma (NPC) after radiation therapy (RT). We identified 14,893 NPC patients and 16,105 other head and neck cancer (HNC) patients treated with RT without thyroidectomy from the National Health Insurance Research Database in Taiwan between 2000 and 2011. Each NPC patient was randomly frequency-matched with four individuals without NPC by age, sex, and index year. Competing-risk regression models were used to estimate hazard ratios (HRs) of hypothyroidism requiring thyroxin associated with NPC after RT. The risk of developing hypothyroidism was significantly higher in the NPC cohort than in the matched cohort (adjusted HR=14.35, 95% CI=11.85-17.37) and the HNC cohort (adjusted HR=2.06, 95% CI=1.69-2.52). Independent risk factors for hypothyroidism among NPC patients included younger age, female sex, higher urbanization level, autoimmune disease, and receipt of chemotherapy. The risk of hypothyroidism requiring thyroxin was significantly higher in NPC patients after RT than in the general Taiwanese population and HNC patients. Regular clinical and serum thyroid function tests are essential among NPC survivors after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Estrogen and Progestin (Hormone Replacement Therapy)

MedlinePlus

... progestin are two female sex hormones. Hormone replacement therapy works by replacing estrogen hormone that is no ... Progestin is added to estrogen in hormone replacement therapy to reduce the risk of uterine cancer in ...

Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor

PubMed Central

Sultan, A; Velaga, M R; Fleet, M; Cheetham, T

2006-01-01

Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign. PMID:16714722

Pericardial Effusion as a Presenting Symptom of Hashimoto Thyroiditis: A Case Report.

PubMed

Leonardi, Alberto; Penta, Laura; Cofini, Marta; Lanciotti, Lucia; Principi, Nicola; Esposito, Susanna

2017-12-14

Background: Hashimoto thyroiditis (HT) is the most frequent cause of acquired hypothyroidism in paediatrics. HT is usually diagnosed in older children and adolescents, mainly in females and is rare in infants and toddlers with cardiac involvement, including pericardial effusion, that can be found in 10% to 30% of adult HT cases. In this paper, a child with HT and pericardial effusion as the most important sign of HT is described. Case presentation : A four-year-old male child suffering for a few months from recurrent abdominal pain sometimes associated with vomiting underwent an abdominal ultrasound scan outside the hospital. This led to the identification of a significant pericardial effusion. At admission, his family history revealed that both his mother and maternal grandmother suffered from HT and that both were treated with l-thyroxine (LT4). The clinical examination did not reveal any pathological signs other than a palpable thyroid. His weight was 21 kg (78th percentile), his height was 101.8 cm (12th percentile) and his body max index (BMI) was 20.26 (96th percentile). On a chest radiograph, his heart had a globular appearance and the lung fields were normal. An echocardiography confirmed and determined the effusion amount (max, 23 mm; 600 mL) with light impairment of the heart kinetics. The ECG showed sinus bradycardia with a normal ST tract. Based on the blood test results, an infectious cause of the pericardial fluid excess was considered unlikely. Thyroid function testing revealed very high thyrotropin (TSH, 487 μIU/mL; normal range, 0.340-5.600 μIU/mL) and low serum-free thyroxine (fT4, 0.04 ng/dL; normal range, 0.54-1.24 ng/dL) levels. High thyroid peroxidase antibody titres in the blood were evidenced (>1500 UI/L; normal values, 0.0-9.0 UI/L). The thyroid ultrasound was consistent with thyroiditis. HT was diagnosed, and LT4 replacement therapy with levothyroxine sodium 1.78 µg/kg/die was initiated, with a gradual increase of the administered dose. The treatment was successful because a complete regression of the effusion after one month was evidenced, with a substantial modification towards normality of the thyroid function tests. One year later, the substitutive therapy led to complete normalization of the thyroid function indexes. A slight reduction of weight (BMI, 17.60 for age) and an increase of the velocity of height growth were evidenced. Conclusions : When fluid is identified in the pericardial space and pericarditis of unknown origin is diagnosed, the thyroid function should be immediately evaluated to prescribe substitutive hormonal therapy if necessary and thereby avoid overt hypothyroidism development and the risk of cardiac tamponade.

Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage.

PubMed

Kopczak, Anna; Kilimann, Ingo; von Rosen, Friedrich; Krewer, Carmen; Schneider, Harald Jörn; Stalla, Günter Karl; Schneider, Manfred

2014-01-01

We performed a screening on patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) to determine the prevalence of post-traumatic hypopituitarism in neurorehabilitation in a cross-sectional, observational single-center study. In addition, the therapeutic consequences of our screening were analyzed retrospectively. From February 2006 to August 2009, patients between 18 and 65 years (n=509) with the diagnosis of TBI (n=340) or SAH (n=169) were screened within two weeks of admittance to neurorehabilitation as clinical routine. Blood was drawn to determine fasting cortisol, free thyroxine (fT4), prolactin, testosterone or estradiol, and insulin-like growth factor I (IGF-I). Patients with abnormalities in the screening or clinical signs of hypopituitarism received further stimulation tests: growth hormone releasing hormone -L-arginine-test and adrenocorticotrophic hormone (ACTH)-test (n=36); ACTH-test alone (n=26); or insulin tolerance test (n=56). In our screening of 509 patients, 28.5% showed lowered values in at least one hormone of the hypothalamus-pituitary axis and 4.5% in two or more axes. The most common disturbance was a decrease of testosterone in 40.7% of all men (in the following 13/131 men were given substitution therapy). Low fT4 was detected in 5.9% (n=3 were given substitution therapy). Low IGF-I was detected in 5.8%, low cortisol in 1.4%, and low prolactin in 0.2%; none were given substitution therapy. Further stimulation tests revealed growth hormone deficiency in 20.7% (n=19/92) and hypocortisolism in 23.7% (n=28/118). Laboratory values possibly indicating hypopituitarism (33%) were common but did not always implicate post-traumatic hypopituitarism. Laboratory values possibly indicating hypopituitarism were common in our screening but most patients were clinically not diagnosed as pituitary insufficient and did not receive hormone replacement therapy. A routine screening of all patients in neurorehabilitation without considering the time since injury, the severity of illness and therapeutic consequences seems not useful.

78 FR 19718 - Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

...] Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use AGENCY: Food...-counter nicotine replacement therapy products, related to concomitant use with other nicotine-containing... over-the- counter nicotine replacement therapy products for their approved intended use as aids to...

Effect of melatonin supplementation on plasma vasopressin response to different conditions in rats with hyperthyroidism induced by L-thyroxine.

PubMed

Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2010-04-09

The present study was performed to determine how basal, isotonic, hypertonic and hypovolemic conditions affect fluid-electrolyte balance and plasma arginine vasopressin (AVP) levels in rats with experimental hyperthyroidism supplemented with melatonin. The rats were divided into four groups of twenty-four subjects each kept under the following treatments during one month: (1) Controls; (2) treated with L-thyroxine; (3) treated with L-thyroxine and sham melatonin and (4) treated with L-thyroxine and melatonin. After this each group was further subdivided into subgroups that were subject to normal, isotonic, hypertonic and hypovolemic conditions. The plasma AVP, total triiodothyronine (TT(3)), total thyroxine (TT(4)) and melatonin levels were measured in plasma by means of a Phoenix Pharmaceutical RIA test kit. Hematocrit and osmolality levels were also determined. There were significant increases of total T3 and T4 levels in the L-thyroxine treated groups, p<0.001. The AVP levels were also increased in groups 2 and 3, but not so in the rats treated with melatonin (p<0.001), which also showed increased plasma melatonin levels (p<0.001). These results indicate that treatment with L-thyroxine increases stimulated and non-stimulated AVP release that are inhibited by melatonin supplementation. It was also shown that AVP response to hypertonic and hypovolemic conditions was not affected by L-thyroxine treatment and/or L-thyroxine+melatonin treatment. Copyright 2009 Elsevier B.V. All rights reserved.

Hormonal treatment and flight feather molt in immature Sandhill Cranes

USGS Publications Warehouse

Gee, G.F.; Lewis, J.C.

1982-01-01

Molt, the production of a new generation of feathers, is a poorly understood physiological phenomenon in nondomestic birds. Often in large birds like geese, flight is restricted by clipping the primary remiges on 1 wing and flight is restored after the molt when the primaries are replaced. A similar technique would be desirable for use with cranes conditioned for release to the native habitat. However, immature sandhill cranes (Grus canadensis) did not appear to replace their primaries annually; therefore, we studied their flight feather molt (from 4 months to 3.5 years of age) and attempted to influence molting. Under natural conditions tail feathers (rectrices) were replaced annually and all secondaries replaced in 2.5-year-old birds. However, replacement of primaries in immature sandhill cranes appears to be a gradual process beginning the 2nd year; about 33% of the original primaries (present at 10 months of age) persisted in the 3.5-year-oId birds. Pulling out the primaries of immature sandhill cranes induces the growth of new primaries, as is true of many other birds. However, the new primaries were incapable of supporting flight, fell out repeatedly, and those that remained were often deformed. Pulling the primaries, under the influence of tranquilizers and anesthetics to relax the feather papillae, also did not induce normal growth of the replacement primaries. Progesterone (including excessively high doses), thyroxine, and follicle stimulating hormone, although effective in inducing feather replacement in domestic poultry, had no effect on crane molt.

Subclinical hyperthyroidism: clinical features and treatment options.

PubMed

Biondi, Bernadette; Palmieri, Emiliano Antonio; Klain, Michele; Schlumberger, Martin; Filetti, Sebastiano; Lombardi, Gaetano

2005-01-01

Subclinical hyperthyroidism appears to be a common disorder. It may be caused by exogenous or endogenous factors: excessive TSH suppressive therapy with L-thyroxine (L-T4) for benign thyroid nodular disease, differentiated thyroid cancer, or hormone over-replacement in patients with hypothyroidism are the most frequent causes. Consistent evidence indicates that 'subclinical' hyperthyroidism reduces the quality of life, affecting both the psycho and somatic components of well-being, and produces relevant signs and symptoms of excessive thyroid hormone action, often mimicking adrenergic overactivity. Subclinical hyperthyroidism exerts many significant effects on the cardiovascular system; it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias, and with an increased left ventricular mass, often accompanied by an impaired diastolic function and sometimes by a reduced systolic performance on effort and decreased exercise tolerance. It is well known that these abnormalities usually precede the onset of a more severe cardiovascular disease, thus potentially contributing to the increased cardiovascular morbidity and mortality observed in these patients. In addition, it is becoming increasingly apparent that subclinical hyperthyroidism may accelerate the development of osteoporosis and hence increased bone vulnerability to trauma, particularly in postmenopausal women with a pre-existing predisposition. Subclinical hyperthyroidism and its related clinical manifestations are reversible and may be prevented by timely treatment.

Hormone replacement therapy in the developing countries.

PubMed

Oei, P L; Ratnam, S S

1998-05-01

The sales data of oestrogen replacement products for 8 developing countries from 1993 to 1995 were analyzed. The data from Malaysia, Pakistan, Taiwan, Thailand, Indonesia, Philippines and South Korea showed the increasing use of oestrogen replacement products. The total usage however varied widely, from only US$11,153 (Philippines in 1993) to as much as US$6,306,717 (Taiwan in 1995). In Singapore, where oestrogen replacement is an accepted and established form of therapy for the postmenopausal woman, there has been an increase in the usage of the nonoestrogen replacement products. There are multiple reasons for the increasing sales of hormone replacement products in the developing countries and these are explored in this article. In some of the developing countries, for example China and India, hormone replacement therapy has just been introduced. However, in those developing countries in which hormone replacement therapy is already available, sales figures show increasing usage. The future augurs well for hormone replacement therapy.

Myxedema coma.

PubMed

Wartofsky, Leonard

2006-12-01

Myxedema coma is the term given to the most severe presentation of profound hypothyroidism and is often fatal in spite of therapy. Decompensation of the hypothyroid patient into a coma may be precipitated by a number of drugs, systemic illnesses (eg, pneumonia), and other causes. It typically presents in older women in the winter months and is associated with signs of hypothyroidism, hypothermia, hyponatremia, hypercarbia, and hypoxemia. Treatment must be initiated promptly in an intensive care unit setting. Although thyroid hormone therapy is critical to survival, it remains uncertain whether it should be administered as thyroxine, triiodothyronine, or both. Adjunctive measures, such as ventilation, warming, fluids, antibiotics, pressors, and corticosteroids, may be essential for survival.

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

Cancerous leptomeningitis and familial congenital hypopituitarism.

PubMed

Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

2016-05-01

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy.

PubMed

Massolt, Elske T; Chaker, Layal; Visser, Theo J; Gillis, Ad J M; Dorssers, Lambert C J; Beukhof, Carolien M; Kam, Boen L R; Franssen, Gaston J; Brigante, Giulia; van Ginhoven, Tessa M; Visser, W Edward; Looijenga, Leendert H J; Peeters, Robin P

2018-01-01

Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. To study if serum miRNA profiles are changed in different thyroid states. We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Mean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment. Although we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.

Iodine-induced thyrotoxicosis--a case for subtotal thyroidectomy in severely ill patients.

PubMed

Köbberling, J; Hintze, G; Becker, H D

1985-01-02

Iodine-induced thyrotoxicosis (IIT), due to iodine application in high amounts in patients with circumscript or disseminated thyroid autonomy, is complicated by a prolonged course, mainly due on the body's resistance to conservative therapy with thiourea derivates. Therefore, we decided to perform subtotal thyroidectomy in 16 thyrotoxic patients. This is in contrast to the common opinion that surgery should only be performed after normalization of thyroid hormones. In all 16 patients with severe IIT, including three patients with thyroid storm, hormone levels decreased within a few days after surgery to normal or subnormal values and the clinical picture of thyrotoxicosis disappeared. In the case of thyroid storm the signs of disorientation normalized within 1-3 days. One patient died 5 weeks after surgery due to severe concomitant diseases. One patient exhibited transitory respiration distress and another had postoperative hypocalcaemia. In nine patients L-thyroxine replacement became necessary because of subclinical or clinical hypothyroidism. Only by this procedure will the high intrathyroidal storage of iodine and performed hormone be extracted. Surgery as a treatment for thyrotoxicosis should be reserved for patients with severe IIT, where conservative treatment has been shown to be ineffective. Furthermore, in rare selected cases, when a rapid normalization is required, surgery without preoperative treatment seems to be justified. The effect of surgery was impressive in all our cases and there were only minor perioperative complications. Thus, it could be shown that subtotal thyroidectomy may be a rational and effective treatment in severe IIT which should be carefully considered and weighed against other types of therapy.

Acute psychosis in a pregnant patient with Graves' hyperthyroidism and anti-NMDA receptor encephalitis.

PubMed

Lu, Jesslyn; Samson, Susan; Kass, Joseph; Ram, Nalini

2015-04-22

A previously healthy 36-year-old woman presented with visual hallucinations and acute psychosis manifested predominantly as hypersexuality. Laboratory testing demonstrated elevated free thyroxine levels, suppressed thyroid-stimulating hormone levels and presence of thyroid-stimulating immunoglobulin and thyroid peroxidase (TPO) antibodies consistent with Graves' disease. Despite achieving biochemical euthyroidism, she remained profoundly hypersexual. She did not respond to additional treatment with antipsychotics and corticosteroids, prompting further evaluation. Cerebrospinal fluid analysis detected pleocytosis, elevated IgG, and presence of antibodies against anti-N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase 65 and TPO. These results suggested a diagnosis of anti-NMDAR encephalitis. Prior to initiation of immunomodulator therapy, she was discovered to be pregnant with date of conception around the time of her original presentation. She received plasmapheresis with resolution of psychosis and decrease in free thyroxine levels. Graves' disease remitted during the remainder of the pregnancy but relapsed 5 months post partum. She has not had further neuropsychiatric symptoms. 2015 BMJ Publishing Group Ltd.

[Oral thyroxine treatment: towards an individually tailored dose].

PubMed

Centanni, Marco; Franchi, Antonella; Santaguida, Maria Giulia; Virili, Camilla; Nardo, Serena; Gargano, Lucilla

2007-09-01

Sodium levothyroxine is one of the most prescribed drugs all over the world. Oral thyroxine treatment is often used lifelong and the search for optimal daily dose may be a challenge for the physician. Patient age and compliance to prescribed regimen are in fact relevant features to achieve therapeutic goal. Also, the absorption of thyroxine is not a linear function of the ingested dose being sensitive to several interferences. Inaccurate administration modality, thyroxine interaction with different drugs, pregnancy, and malabsorption are all possible causes of increased need for thyroxine. Important and simple evidences are now available to improve the accuracy of drug administration and optimize the treatment. In fact, recent evidence pointed out the role of gastric acid secretion on the subsequent intestinal absorption of thyroxine in relation with the timing of food ingestion as well as with pH impairment associated to frequent gastric disorders like Helicobacter pylori infection and gastric atrophy.

Effect on smoking cessation of switching nicotine replacement therapy to over-the-counter status.

PubMed

Thorndike, Anne N; Biener, Lois; Rigotti, Nancy A

2002-03-01

This study examined whether the change in nicotine replacement therapy sales from prescription to over the counter (OTC) status affected smoking cessation. We used the 1993-1999 Massachusetts Tobacco Surveys to compare data from adult current smokers and recent quitters before and after the OTC switch. No significant change over time occurred in the proportion of smokers who used nicotine replacement therapy at a quit attempt in the past year (20.1% pre-OTC vs 21.4% post-OTC), made a quit attempt in the past year (48.1% vs 45.2%), or quit smoking in the past year (8.1% vs 11.1%). Fewer non-Whites used nicotine replacement therapy after the switch (20.7% pre-OTC vs 3.2% post-OTC, P =.002), but the proportion of Whites using nicotine replacement therapy did not change significantly (20.6% vs 24.0%). We observed no increase in Massachusetts smokers' rates of using nicotine replacement therapy, making a quit attempt, or stopping smoking after nicotine replacement therapy became available for OTC sale. There appear to be other barriers to the use of nicotine replacement therapy besides visiting a physician, especially among minority smokers.

Bilateral Keratoconus Induced by Secondary Hypothyroidism After Radioactive Iodine Therapy.

PubMed

Lee, Ramon; Hafezi, Farhad; Randleman, J Bradley

2018-05-01

To present a case of new-onset, bilateral, rapidly progressive keratoconus induced by secondary hypothyroidism after radioactive iodine therapy during the sixth decade of life that was successfully treated with corneal cross-linking. Case report and literature review. A 53-year-old woman with no ocular complaints but with a history of Graves' disease and thyrotoxicosis was treated with radioactive iodine therapy and oral levothyroxine for secondary acquired hypothyroidism 3 years prior. Initially, uncorrected distance visual acuity (UDVA) was 20/40 and corrected distance visual acuity (CDVA) was 20/25 in both eyes. Over the following 3 years, the patient developed worsening UDVA and CDVA, with increasing manifest astigmatism of greater than 7.00 diopters (D) in the right eye and 4.75 D in the left eye, with corneal thinning and focal steepening and was diagnosed as having bilateral progressive keratoconus. The patient underwent sequential corneal cross-linking with resultant postoperative CDVA of 20/20 and reduced maximum keratometry and manifest astigmatism in both eyes. The patient's thyroid levels were within normal limits throughout the clinical course. This case provides evidence of the relationship between keratoconus development and thyroid gland dysfunction. The pathophysiology of this relationship has yet to be completely elucidated, but elevated levels of thyroxine in the aqueous humor and tear film and thyroxine receptors in the cornea likely play a role. Screening topographies for patients with thyroid gland dysfunction may be of value for these higher risk patients. [J Refract Surg. 2018;34(5):351-353.]. Copyright 2018, SLACK Incorporated.

Establishing a reference range for triiodothyronine levels in preterm infants.

PubMed

Oh, Ki Won; Koo, Mi Sung; Park, Hye Won; Chung, Mi Lim; Kim, Min-ho; Lim, Gina

2014-10-01

Thyroid dysfunction affects clinical complications in preterm infants and older children. However, thyroid hormone replacement in preterm infants has no proven benefits, possibly owing to the lack of an appropriate reference range for thyroid hormone levels. We aimed to establish a reference range for triiodothyronine (T3) levels at 1-month postnatal age (PNA) in preterm infants. This retrospective study included preterm infants born at a tertiary referral neonatal center at gestational age (GA)<35 weeks with no apparent thyroid dysfunction, for 6 consecutive years, with follow-up from PNA 2 weeks to 16 weeks. Using thyroid function tests (TFT), the relationships between T3 levels and thyrotropin (TSH) and free thyroxine (fT4) levels, birth weight, GA, postmenstrual age (PMA), and PNA were examined. The conversion trend for fT4 to T3 was analyzed using the T3/fT4 ratio. Overall, 464 TFTs from 266 infants were analyzed, after excluding 65 infants with thyroid dysfunction. T3 levels increased with fT4 levels, birth weight, GA, PMA, and PNA but not with TSH levels. The T3/fT4 ratio also increased with GA, PNA, and PMA. The average T3 level at 1 month PNA was 72.56 ± 27.83 ng/dL, with significant stratifications by GA. Relatively low T3 and fT4 levels in preterm infants were considered normal, with T3 levels and conversion trends increasing with GA, PMA, and PNA. Further studies are required to confirm the role of the present reference range in thyroid hormone replacement therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

PubMed

Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

2016-02-01

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

PubMed

Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

[Effect of space flight aboard "Kosmos-1129" on thyroid hormone content of the blood and thyroid gland of rats].

PubMed

Tigranian, R A; Kalita, N F; Makho, L; Langer, P; Knopp, Ia

1985-01-01

Thyrotrophin, thyroxine, triiodothyronine, and reverse triiodothyronine were measured in plasma and thyroxine and triiodothyronine in the thyroid gland of the rats flown for 18.5 days onboard Cosmos-1129. Postflight the plasma content of thyrotrophin and triiodothyronine increased and that of thyroxine decreased and the gland content of thyroxine and triiodothyronine diminished. It is postulated that in the flight animals the functional activity of the thyroid gland declined.

Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

PubMed

Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

2013-10-01

There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate <20 mL/min (p < 0.0001), <15 mL/min (p < 0.0001) and <12 mL/min (p = 0.002). When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p < 0.05; 95% confidence interval = 1.14-2.13). A total of 47% of conservative management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

Thyroxine Induced Resorption of Xenopus Laevis Tail Tissue in Vitro.

ERIC Educational Resources Information Center

Scadding, Steven R.

1984-01-01

A simple method of studying thyroxine-induced resorption of tadpole tails in vitro is described. This procedure demonstrates that resorption is dependent on thyroxine and requires protein synthesis. It introduces students to the use of tissue culture methods. (Author)

Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism.

PubMed

Abbas, Amr M; Sakr, Hussein F

2016-04-01

Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

PubMed

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mL

Thyroxine: effects of neonatal administration on maturation, development, and behavior.

PubMed

Schapiro, S; Norman, R J

1967-03-10

Thyroxine was administered to infant rats within the first 3 days of postnatal life; controls receiving 0.01N NaOH were from the same litter. Thyroxine accelerated the maturation of the pituitary-adrenal response to elec tric shock. The "startle response" ap peared earlier in the experimental ani mals, as did the development and re sponse of the electroencephalogram to novel stimuli. The thyroxine-treated rats, when 16 to 18 days old, acquired a conditioned-avoidance response faster than did controls.

Plasma thyroxine changes of the Apollo Crewman.

PubMed

Sheinfeld, M; Leach, C S; Johnson, P C

1975-01-01

Blood drawn from Apollo crew member; to the mission, at recovery, and postmission was used to examine the effect Apollo mission activities have on tyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that apollo activities and environment caused the postmission increase in serum cholesterol may be one result of the increased thyroxine activity.

Effect on Smoking Cessation of Switching Nicotine Replacement Therapy to Over-the-Counter Status

PubMed Central

Thorndike, Anne N.; Biener, Lois; Rigotti, Nancy A.

2002-01-01

Objectives. This study examined whether the change in nicotine replacement therapy sales from prescription to over the counter (OTC) status affected smoking cessation. Methods. We used the 1993–1999 Massachusetts Tobacco Surveys to compare data from adult current smokers and recent quitters before and after the OTC switch. Results. No significant change over time occurred in the proportion of smokers who used nicotine replacement therapy at a quit attempt in the past year (20.1% pre-OTC vs 21.4% post-OTC), made a quit attempt in the past year (48.1% vs 45.2%), or quit smoking in the past year (8.1% vs 11.1%). Fewer non-Whites used nicotine replacement therapy after the switch (20.7% pre-OTC vs 3.2% post-OTC, P = .002), but the proportion of Whites using nicotine replacement therapy did not change significantly (20.6% vs 24.0%). Conclusions. We observed no increase in Massachusetts smokers' rates of using nicotine replacement therapy, making a quit attempt, or stopping smoking after nicotine replacement therapy became available for OTC sale. There appear to be other barriers to the use of nicotine replacement therapy besides visiting a physician, especially among minority smokers. (Am J Public Health. 2002;92:437–442) PMID:11867326

Development of a vancomycin dosing approach for critically ill patients receiving hybrid hemodialysis using Monte Carlo simulation.

PubMed

Lewis, Susan J; Mueller, Bruce A

2018-01-01

Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted "in silico" vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC 24h ) of 400-700 mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. An initial vancomycin dose of 15 or 20 mg/kg immediately followed by 15 mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC 24h of ≥400 mg·h/L for ≥90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC 24h of ≥700 mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%-88% of patients achieved AUC 24h of 400-700 mg·h/L. An initial loading dose of 15-20 mg/kg followed by a maintenance regimen of 15 mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

PubMed

Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

2014-01-01

Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study.

PubMed

Korevaar, Tim I M; Muetzel, Ryan; Medici, Marco; Chaker, Layal; Jaddoe, Vincent W V; de Rijke, Yolanda B; Steegers, Eric A P; Visser, Theo J; White, Tonya; Tiemeier, Henning; Peeters, Robin P

2016-01-01

Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Kuni, C.C.; Klingensmith, W.C. III

Thirteen patients received an initial dose of 25-29.9 mCi (925-1106 MBq) of /sup 131/I following partial thyroidectomy for papillary, follicular, or mixed carcinoma. Administration of thyroxine (T/sub 4/) or triiodothyronine (T/sub 3/) was stopped 3-12 weeks and 1-6 weeks, respectively, before therapy or imaging. Patients remained on normal diets and did not receive thyroid stimulating hormone (TSH) or diuretics. Follow-up 3 months to 2 years after therapy demonstrated that ablation of thyroid bed activity was successful in only one patient, who still had metastases. This suggests that administration of 25-29.9 mCi of /sup 131/I following surgery is unreliable for ablationmore » of residual thyroid bed activity.« less

[Treatment with sunitinib and hypothyroidism--a case report and overview of literature].

PubMed

Kreze, A; Stáhalová, V; Zadrazilová, A; Koskuba, J; Kosák, M

2009-01-01

In the article the authors present the case of a patient with clear cell renal carcinoma, where after nephrectomy local metastases appeared. The treatment of choice was sunitinib. After 20 cycles of therapy heavy hypothyroidism was verified which required substitution by thyroxine. Elevated levels of TSH appeared in up to 70% and hypothyrodism in up to 40% of thus treated patients. Also described is the mechanism of action of sunitinib. There seems to exist a correlation between the "adverse effects" of the drug and a better result of the therapy of cancer, however, prospective studies are absent. Most experts agree that the thyroid function during treatment with sunitinib needs to be monitored.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

PubMed

Zappitelli, Michael; Goldstein, Stuart L; Symons, Jordan M; Somers, Michael J G; Baum, Michelle A; Brophy, Patrick D; Blowey, Douglas; Fortenberry, James D; Chua, Annabelle N; Flores, Francisco X; Benfield, Mark R; Alexander, Steven R; Askenazi, David; Hackbarth, Richard; Bunchman, Timothy E

2008-12-01

Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. Retrospective database study. Multicenter study in pediatric critical care units. Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. None. Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Assessment of a method for measuring serum thyroxine by radioimmunoassay, with use of polyethylene glycol precipitation. [/sup 125/I tracer technique

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

Farid, N.R.; Kennedy, C.

We assessed the efficacy of a new thyroxine radioimmunoassay kit (Abbott) in which polyethylene glycol is used to separate bound from free hormone. Mean serum thyroxine was 88 +- 15 (+-SD) ..mu..g/liter for 96 normal persons. Results for hypothyroid and hyperthyroid persons were clearly separated from those for normal individuals. Women taking oral contraceptive preparations showed variable increases in their serum thyroxine values. The coefficient of variation ranged from 1 to 3% within assay and from 5.4 to 11% among different assays. Excellent parallelism was demonstrated between thyroxine values estimated by this method and those obtained either by competitive proteinmore » binding or by a separate radioimmunoassay for the hormone.« less

Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

PubMed

Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

2017-02-01

Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

Hormonal control of angiotensinogen production.

PubMed

Dzau, V J; Herrmann, H C

The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was used to study the hormonal control of angiotensinogen synthesis and release in the rat. Dexamethasone administration in vivo resulted in increase in the in vitro rate of release of angiotensinogen by liver slices into the incubation media. This increase was inhibited by actinomycin D, an inhibitor of protein synthesis and vincristine which blocks secretion. Similarly, ethinyl estradiol treatment resulted in a 50% increase in angiotensinogen production. Hyperthyroid state was achieved by injecting rats with L-thyroxine daily for seven days. Hepatic production rate of angiotensinogen rose 21/2-fold above control and was accompanied by increases in plasma angiotensinogen concentration and plasma renin activity. In contrast, plasma angiotensinogen concentration and plasma renin activity were reduced in thyroidectomized rats. The rate of angiotensinogen production by liver slices of these rats decreased by five-fold below that of intact animals. These changes were largely corrected when thyroidectomized rats were treated with replacement doses of L-thyroxine. We conclude that hepatic angiotensinogen biosynthesis is under hormonal control. Glucocorticoid, estrogen and thyroid hormones all stimulate angiotensinogen production. These results may in part explain the pathogenesis of hypertension associated with certain disease states.

Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

NASA Technical Reports Server (NTRS)

Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

1976-01-01

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

Introduction of a rapid, simple radioimmunoassay and quality control scheme for thyroxine.

PubMed Central

Nye, L; Hassan, M; Willmott, E; Landon, J

1976-01-01

A simple radioimmunoassay has been developed for service purposes to determine serum total thyroxine levels. Only three additions are required, of standard or sample, labelled thyroxine and antibody in polyethylene glycol. After 2 hours' incubation at room temperature the antibody-bound and free fractions are separated by centrifugation. Serum total thyroxine levels were measured in 195 euthyroid subjects and it was established that normal values lay within the range 57 to 155 nmol/1. Serial blood samples taken over a 24-hour period, from 11 subjects, indicated that there was no circadian rhythm so that samples for total thyroxine assay can be taken at any time of the day. Similar results were obtained using serum or plasma. Satisfactory results were obtained for three quality control sera when measured by seven different laboratories using this method. PMID:932232

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.

PubMed

Bhatt, Parloop; Makwana, Dharmesh; Santani, Devdas; Goyal, Ramesh

2007-05-01

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

PubMed

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Mild neonatal hyperthyrotrophinaemia: 10-year experience suggests the condition is increasingly common but often transient.

PubMed

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

2013-12-01

To examine a large population of infants with mild neonatal hyperthyrotrophinaemia (MNH) and determine prevalence, clinical characteristics and treatment history. Retrospective study of infants with MNH followed at The Hospital for Sick Children between 2000 and 2011. MNH was defined by an abnormal newborn screen followed by thyroid-stimulating hormone (TSH) between 5 and 30 mU/l and normal free T4 (FT4) on confirmatory tests. Mild neonatal hyperthyrotrophinaemia represented 22·3% of patients (103/462; 60 boys, 43 girls) within our clinic. Incidence increased from two of 20 in 2000 to 31 of 74 cases in 2010. Seventy eight percent of patients started L-thyroxine (initial dose: 8·3 ± 2·5 mcg/kg). The treated group had higher confirmatory TSH levels (P = 0·001) and had undergone thyroid scintigraphy more often (P = 0·0001) compared with the nontreated group. Evidence of overtreatment was detected in 45% of thyroid function tests obtained during treatment. Among the treated infants who had reached 3 years of age, 45% (N = 14) underwent a trial-off medication. Compared with those not trialled-off therapy, these infants were less likely to have had dose escalations during treatment (P = 0·001). The trial-off treatment was successful in 50% of cases. In the subset of infants with confirmatory TSH >10 mU/l, trial-off therapy was successful in 40%. None of the assessed variables predicted success of trial-off therapy. Mild neonatal hyperthyrotrophinaemia is an increasingly common diagnosis. It is more common in males and is often transient, but predictors of success of trial-off therapy were not identified. Further studies are needed to determine optimum L-thyroxine dosing and to determine whether treatment improves neurocognitive outcomes. © 2013 John Wiley & Sons Ltd.

Reversible primary hypothyroidism in Japanese patients undergoing maintenance hemodialysis.

PubMed

Sanai, T; Inoue, T; Okamura, K; Sato, K; Yamamoto, K; Abe, T; Node, K; Tsuruya, K; Iida, M

2008-02-01

The presence or absence of hypothyroidism was assessed in 152 consecutive Japanese patients with end-stage renal disease on hemodialysis. Eight patients who had undergone treatment for thyroid disease before starting hemodialysis therapy, and 3 patients with amyloidosis due to rheumatoid arthritis were excluded. Of the remaining 141 hemodialysis patients, 14 (9.9%) (9 males and 5 females, aged 69.1 A+/- 8.8 years with a mean duration of hemodialysis of 69 A+/- 51 months) were in a hypothyroid state, defined as a thyroid-stimulating hormone (TSH) level > 5 mU/l. Antithyroid peroxidase antibodies were positive in only 1 of the 14 patients, while antithyroglobulin antibodies were negative in all of these patients. After iodide restriction, the serum TSH level decreased in all the patients from a mean of 16.49 A+/- 22.80 to 4.44 A+/- 3.35 mU/l after 1 month, 4.25 A+/- 2.24 mU/l after 2 months and 3.97 A+/- 2.22 mU/l after 3 months. The 3 months of iodide restriction were also associated with decreases in systolic blood pressure (142 A+/- 19 to 125 A+/- 16 mmHg, p < 0.05), diastolic blood pressure (79 A+/- 13 to 72 A+/- 9 mmHg, p < 0.05) and thyroid gland volume estimated by ultrasonography (13.7 A+/- 6.3 to 11.6 A+/- 5.2 ml, p < 0.05). A high prevalence of reversible primary hypothyroidism was found in end-stage renal disease patients on hemodialysis. Retention of excess iodide may be the mechanism responsible for reversible hypothyroidism rather than immunological perturbations. It is, therefore, recommended to attempt iodide restriction before starting l-thyroxine replacement therapy.

Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up.

PubMed

Larizza, Daniela; Albanesi, Michela; De Silvestri, Annalisa; Accordino, Giulia; Brazzelli, Valeria; Maffè, Gabriella Carnevale; Calcaterra, Valeria

2016-05-01

Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests.

PubMed

Quante, Saskia; Fracassi, Federico; Gorgas, Daniela; Kircher, Patrick R; Boretti, Felicitas S; Ohlerth, Stefanie; Reusch, Claudia E

2010-06-01

A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

AN ITALIAN SURVEY OF COMPLIANCE WITH MAJOR GUIDELINES FOR L-THYROXINE OF PRIMARY HYPOTHYROIDISM.

PubMed

Vezzani, Silvia; Giannetta, Elisa; Altieri, Barbara; Barbonetti, Arcangelo; Bellastella, Giuseppe; Certo, Rosaria; Cignarelli, Angelo; Cinti, Francesca; D'Andrea, Settimio; Di Dalmazi, Giulia; Frara, Stefano; Garelli, Silvia; Giuffrida, Giuseppe; Maiorino, Maria Ida; Mele, Chiara; Mezza, Teresa; Pani, Maria Grazia; Samà, Maria Teresa; Satta, Chiara; Santi, Daniele

2018-05-01

The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment. This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology. The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers. Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment. AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography.

Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism.

PubMed

Rasic-Milutinovic, Z; Jovanovic, D; Bogdanovic, G; Trifunovic, J; Mutic, J

2017-02-01

Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism.Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution. © Georg Thieme Verlag KG Stuttgart · New York.

Development of targeted therapy and immunotherapy for treatment of small cell lung cancer.

PubMed

Saito, Motonobu; Shiraishi, Kouya; Goto, Akiteru; Suzuki, Hiroyuki; Kohno, Takashi; Kono, Koji

2018-05-14

Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC. Recent advances in the understanding of molecular biology have revealed several candidate therapeutic targets. To date, poly [ADP-ribose] polymerase (PARP), enhancer of zeste homologue 2 (EZH2) or delta-like canonical Notch ligand 3 (DLL3) are considered to be druggable targets in SCLC. In addition, another candidate of personalized therapy for SCLC is immune blockade therapy of programmed death-1 (PD-1) and its ligand, PD-L1. PD-1/PD-L1 blockade therapy is not a standard therapy for SCLC, so many clinical trials have been performed to investigate its efficacy. Herein, we review gene aberrations exploring the utility of targeted therapy and discuss blockade of immune checkpoints therapy in SCLC.

Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4.

PubMed

Filges, Isabel; Bischof-Renner, Andrea; Röthlisberger, Benno; Potthoff, Christian; Glanzmann, René; Günthard, Joëlle; Schneider, Jacques; Huber, Andreas R; Zumsteg, Urs; Miny, Peter; Szinnai, Gabor

2012-02-01

Clinical presentation of hypopituitarism in the neonate may be variable, ranging from absent to severe nonspecific symptoms and may be life-threatening in patients with adrenocorticotropic hormone deficiency. The LIM homeobox gene 4 (LHX4) transcription factor regulates early embryonic development of the anterior pituitary gland. Autosomal dominant mutations in LHX4 cause congenital hypopituitarism with variable combined pituitary hormone deficiency (CPHD). We report on a neonate with unexplained heart failure and minor physical anomalies, suggesting a midline defect. She was diagnosed with complete CPHD. Cardiac function was rescued by replacement with hydrocortisone and thyroxine; hypoglycaemia stopped under growth hormone therapy. Magnetic resonance imaging revealed a dysgenetic pituitary gland suggesting an early developmental defect. Array comparative genomic hybridization showed a maternally inherited 1.5-megabase microdeletion in 1q25.2q25.3, including the LHX4 gene. Haploinsufficiency of LHX4 likely explains the predominant pituitary phenotype in the proposita and we suggest variable intrafamilial penetrance of the inherited microdeletion. To the best of our knowledge, we are the first to report on heart failure as a rare nonspecific symptom of treatable CPHD in the newborn. Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.

Success of smoking cessation interventions during pregnancy.

PubMed

Bérard, Anick; Zhao, Jin-Ping; Sheehy, Odile

2016-11-01

Smoking during pregnancy is a modifiable risk factor associated with adverse pregnancy outcomes. Smoking during pregnancy has been shown to increase the risk of spontaneous abortion, prematurity, low birthweight, congenital malformations, and sudden infant death syndrome. Despite the fact that it is well known that smoking can lead to adverse pregnancy outcomes, 13-25% of pregnant women overall continue to smoke during this critical period. The objective of the study was to evaluate the effect of gestational use of bupropion and nicotine patch replacement therapy on the risk of the following: (1) smoking cessation, (2) prematurity, and (3) small for gestational age. Women included in the Quebec Pregnancy Cohort who filled the annual autoadministered questionnaire between Jan. 1, 1998, and June 30, 2009, were studied. Smokers before gestation with a pregnancy resulting in a live birth comprised the study population. Three mutually exclusive study groups were formed among those who smoked at the beginning of pregnancy: gestational users of nicotine patch replacement therapy, bupropion, and smokers who did not use nicotine patch replacement therapy or bupropion. Rate of smoking cessation during pregnancy as well as the risk of prematurity and small for gestational age were studied. Of the 1288 women who met inclusion criteria, 900 were smokers, 72 were bupropion users, and 316 were nicotine patch replacement therapy users. Bupropion and nicotine patch replacement therapy use during pregnancy were associated with higher rates of smoking cessation: 81% in the bupropion group; 79% for nicotine patch replacement therapy; and 0% in those not using buproprion or nicotine patch replacement therapy. After discontinuing smoking cessation medications, 60% of bupropion users and 68% of nicotine patch replacement therapy users did not smoke again during and after pregnancy. Adjusting for potential confounders, nicotine patch replacement therapy use was associated with a lower risk of prematurity (adjusted odds ratio, 0.21, 95% confidence interval, 0.13-0.34), and small-for-gestational-age (adjusted odds ratio, 0.61, 95% confidence interval, 0.41-0.90) compared to smoking. Bupropion was associated with a lower risk of prematurity only (adjusted odds ratio, 0.12, 95% confidence interval, 0.03-0.50). Bupropion and nicotine patch replacement therapy have an impact on smoking cessation during and after pregnancy. Nicotine patch replacement therapy also decreased the risk of prematurity and small for gestational age. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypothyroidism presenting as destructive arthropathy of the fingers.

PubMed Central

Gerster, J. C.; Quadri, P.; Saudan, Y.

1985-01-01

A patient presenting with destructive arthropathy of the proximal interphalangeal (PIP) joints of the hands is described. She was initially believed to have rheumatoid arthritis but non-steroidal anti-inflammatory drugs were of no help. The patient was subsequently found to have hypothyroidism and erosive osteoarthritis of the fingers. Joint swelling, pain and stiffness responded dramatically to thyroid hormone substitution. The PIP joint spaces reappeared on the radiographs within 9 months. This case suggest that hypothyroidism may induce destructive arthropathy of the finger joints. As thyroxine replacement may reverse the rheumatic complaints, hypothyroidism should be considered in the differential diagnosis of a destructive arthropathy of unclear aetiology. Images Figure 1 Figure 2 PMID:3983045

Effects of thyroxine and dexamethasone on rat submandibular glands

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

Sagulin, G.B.; Roomans, G.M.

1989-08-01

Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular salivamore » was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol.« less

Hormone replacement therapy and risk of malignancy.

PubMed

Diamanti-Kandarakis, Evanthia

2004-02-01

The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.

Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction.

PubMed

Hua, Xu; Cao, Xin-Yuan; Wang, Xiao-Li; Sun, Peng; Chen, Ling

2017-11-01

Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic β-cells with reduced homeostasis model assessment (HOMA)-β index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPARγ and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPARγ and GLUT4 expression, and Akt phosphorylation. Activation of PPARγ by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPARγ and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (≥8 mg/kg) results in insulin resistance via thyroid hormones reduction. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hormone Replacement Therapy and Your Heart

MedlinePlus

Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand potential risks to your heart and whether hormone therapy is right for you. By Mayo Clinic Staff ...

Structural mechanism for the carriage and release of thyroxine in the blood.

PubMed

Zhou, Aiwu; Wei, Zhenquan; Read, Randy J; Carrell, Robin W

2006-09-05

The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family of protease inhibitors, thyroxine-binding globulin (TBG) and corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo thyroxine, solved here at 2.8 A, shows how the thyroxine is carried in a surface pocket on the molecule. This unexpected binding site is confirmed by mutations associated with a loss of hormone binding in both TBG and also homologously in corticosteroid-binding globulin. TBG strikingly differs from other serpins in having the upper half of its main beta-sheet fully opened, so its reactive center peptide loop can readily move in and out of the sheet to give an equilibrated binding and release of thyroxine. The entry of the loop triggers a conformational change, with a linked contraction of the binding pocket and release of the bound thyroxine. The ready reversibility of this change is due to the unique presence in the reactive loop of TBG of a proline that impedes the full and irreversible entry of the loop that occurs in other serpins. Thus, TBG has adapted the serpin inhibitory mechanism to give a reversible flip-flop transition, from a high-affinity to a low-affinity form. The complexity and ready triggering of this conformational mechanism strongly indicates that TBG has evolved to allow a modulated and targeted delivery of thyroxine to the tissues.

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

PubMed

Beer, Meinrad; Weidemann, Frank; Breunig, Frank; Knoll, Anita; Koeppe, Sabrina; Machann, Wolfram; Hahn, Dietbert; Wanner, Christoph; Strotmann, Jörg; Sandstede, Jörn

2006-05-15

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

PubMed

Zwaveling-Soonawala, Nitash; Witteveen, M Emma; Marchal, Jan Pieter; Klouwer, Femke C C; Ikelaar, Nadine A; Smets, Anne M J B; van Rijn, Rick R; Endert, Erik; Fliers, Eric; van Trotsenburg, A S Paul

2017-05-01

The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P  = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) ( P  = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower ( P  < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia. © 2017 European Society of Endocrinology.

Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

PubMed

Mazziotti, G; Mormando, M; Cristiano, A; Bianchi, A; Porcelli, T; Giampietro, A; Maffezzoni, F; Serra, V; De Marinis, L; Giustina, A

2014-06-01

In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. Cross-sectional study. We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  μg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  μg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: <0.93  μg/kg per day). Such a difference was not observed in patients with untreated GHD who showed a higher prevalence of vertebral fractures regardless of l-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% CI 1.27-14.33; P=0.01) and the daily dose of l-T4 (odds ratio: 4.01, 95% CI 1.16-14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism. Our data suggest for the first time that a relative overtreatment with l-T4 may influence the fracture risk in some patients with hypopituitarism. © 2014 European Society of Endocrinology.

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

PubMed

Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours; (3) T3S may represent a new agent in combination with T4 in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.

Hypercalcaemia in a dog with primary hypothyroidism.

PubMed

Lobetti, R G

2011-12-01

A 7-year-old female beagle was evaluated for symptomatic hypercalcaemia and primary hypothyroidism. Clinical findings were typical for hypothyroidism. Plasma parathyroid hormone was low and obvious causes for the hypercalcaemia were ruled out by means of abdominal ultrasonography, ultrasonography of the parathyroid glands, survey thoracic radiographs, and fine needle aspirate cytology of the spleen, liver, and peripheral lymph nodes. Treatment with thyroxine resulted in resolution of the hypercalcaemia after approximately 9 weeks of therapy. This is the 1st report of primary adult-onset hypothyroidism associated with symptomatic hypercalcaemia in a dog.

Stimulation of thyroid hormone secretion by thyrotropin in beluga whales, Delphinapterus leucas.

PubMed Central

St Aubin, D J

1987-01-01

Bovine thyroid stimulating hormone administered to three beluga whales, Delphinapterus leucas, was effective in producing an increase in circulating levels of triiodothyronine and thyroxine. A single dose of 10 I.U. of thyroid stimulating hormone resulted in a 145% increase in triiodothyronine and a 35% increase in thyroxine after nine hours in a whale tested within two hours after capture. The response was less pronounced in an animal tested with the same does on two occasions after four and eight weeks in captivity. In the third whale, 10 I.U. of thyroid stimulating hormone given on each of three consecutive days produced a marked increase in triiodothyronine and thyroxine. The elevation of thyroxine concentration persisted for at least two days after the last injection of thyroid stimulating hormone. A subsequent decrease in thyroxine to levels below baseline signalled the suppression of endogenous thyroid stimulating hormone. This preliminary study helps to establish a protocol for testing thyroid function in cetaceans. PMID:3651900

Dietary hyperthyroidism in dogs.

PubMed

Köhler, B; Stengel, C; Neiger, R

2012-03-01

Evaluation of dogs with elevated plasma thyroxine concentration fed raw food before and after changing the diet. Between 2006 and 2011 all dogs presented with an elevated plasma thyroxine concentration and a dietary history of feeding raw food were included. Thyroxine (reference interval: 19·3 to 51·5 nmol/L) and in many cases also thyroid-stimulating hormone concentrations (reference interval: <0·30 ng/mL) were measured initially and after changing the diet. Twelve dogs were presented with a median age of five years. The median plasma thyroxine concentration was 156·1 (range of 79·7 to 391·9) nmol/L; in six dogs, thyroid-stimulating hormone concentration was measured and was <0·03 ng/mL in five dogs and 0·05 ng/mL in one dog. Six dogs showed clinical signs such as weight loss, aggressiveness, tachycardia, panting and restlessness while six dogs had no clinical signs. After changing the diet eight dogs were examined: thyroxine concentration normalised in all dogs and clinical signs resolved. Dietary hyperthyroidism can be seen in dogs on a raw meat diet or fed fresh or dried gullets. Increased plasma thyroxine concentration in a dog, either with or without signs of hyperthyroidism, should prompt the veterinarian to obtain a thorough dietary history. © 2012 British Small Animal Veterinary Association.

Dry olive leaf extract counteracts L-thyroxine-induced genotoxicity in human peripheral blood leukocytes in vitro.

PubMed

Topalović, Dijana Žukovec; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Dekanski, Dragana; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.

Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood Leukocytes In Vitro

PubMed Central

Žukovec Topalović, Dijana; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger. PMID:25789081

Identification of genes mediating thyroid hormone action in the developing mouse cerebellum.

PubMed

Takahashi, Masaki; Negishi, Takayuki; Tashiro, Tomoko

2008-02-01

Despite the indispensable role thyroid hormone (TH) plays in brain development, only a small number of genes have been identified to be directly regulated by TH and its precise mechanism of action remains largely unknown, partly because most of the previous studies have been carried out at postnatal day 15 or later. In the present study, we screened for TH-responsive genes in the developing mouse cerebellum at postnatal day 4 when morphological alterations because of TH status are not apparent. Among the new candidate genes selected by comparing gene expression profiles of experimentally hypothyroid, hypothyroid with postnatal thyroxine replacement, and control animals using oligoDNA microarrays, six genes were confirmed by real-time PCR to be positively (orc1l, galr3, sort1, nlgn3, cdk5r2, and zfp367) regulated by TH. Among these, sort1, cdk5r2, and zfp367 were up-regulated already at 1 h after a single injection of thyroxine to the hypothyroid or control animal, suggesting them to be possible primary targets of the hormone. Cell proliferation and apoptosis examined by BrdU incorporation and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay revealed that hypothyroidism by itself did not enhance apoptosis at this stage, but rather increased cell survival, possibly through regulation of these newly identified genes.

Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

PubMed

Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

2013-07-01

Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

Constituents of smoke from cigarettes made from diverted nicotine replacement therapy patches.

PubMed

Morrissey, Hana; Ball, Patrick; Boland, Martin; Hefler, Marita; Thomas, David P

2016-03-01

Anecdotes of nicotine replacement therapy patch misuse associated with the introduction of smoke-free prisons have been reported by media internationally, including Canada in 2006, New Zealand in 2011 and Australia in 2014. This study identifies chemical compounds released through diverted nicotine replacement therapy patches when they are smoked. Two samples were produced: (i) shredded 21 mg nicotine replacement therapy patches rolled with tea leaves into a cigarette; and (ii) patches boiled in water and tea leaves, and then dried tea leaves rolled into a cigarette. The smoke was tested for nicotine, caffeine and toxins. High-performance liquid chromatography, mass spectrometry and spectrophotometry were used to detect the presence and quantity of nicotine and caffeine. A specialised laboratory was contracted to test the presence of toxins. Nicotine was liberated when the two samples were burnt but not if the nicotine replacement therapy patches were boiled in water alone. High concentrations of formaldehyde, acetaldehyde, acrolein, toluene, xylene and heavy metals were also released. Nicotine is released when diverted nicotine replacement therapy patches are smoked, as are caffeine and harmful toxins. These toxins have the potential to cause short- and long-term health damage. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial.

PubMed

Smith, Orla M; Wald, Ron; Adhikari, Neill K J; Pope, Karen; Weir, Matthew A; Bagshaw, Sean M

2013-10-05

Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation. This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO₂/FiO₂<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events). The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial. NCT01557361.

Common autoimmune biomarkers, thyroid hormonal abnormalities, and beta cells dysfunction in patients with latent autoimmune diabetes in adults with type II diabetes mellitus.

PubMed

Yousefzadeh, Gholamreza; Gozashti, Mohammadhossein; Najafipour, Hamid; Gholamhosseinian, Najar Ahmad; Bahramnejad, Abbas; Shokouhi, Mostafa

2016-01-01

Latent autoimmune diabetes in adults (LADA) is autoimmune diabetes with a slow progression characterized by the presence of antibodies associated with Type I diabetes. The present study aimed to assess autoimmune characteristics in patients with LADA in Iran. We attempted to obtain a clear view of autoimmune conditions in LADA among our population. This study was sourced from the population-based survey of KERCARDS aiming assessment of cardiovascular risk factors among a great sample of Iranian population who were resident in Kerman, a great province in southern Iran. Among all diabetic patients who were negative for Anti Glutamic Acid Decarboxylase (GAD) antibody test, 120 were selected as the controls and among 80 patients who were positive for this test diagnosed as LADA, the recorded files of 57 patients were complete considered as the cases. The level of thyroxin is significantly lower in patients with LADA compared with the controls so 73.7% and 45% of patients had normal level of thyroxin, respectively. Also, those with LADA had considerably lower levels of both thyroid peroxydaseantibody (TPO-Ab) and C-peptide when compared with non-LADA group. Using multivariate analyses and with the presence of baseline variables including gender, age, and duration of disease, the diagnosis of LADA was associated with lower serum levels of Anti-TPO, C-peptide, and thyroxin, but not associated with the level of Anti-TTG in serum. LADA patients may face with lower serum levels of C-peptide and thyroid-specific antibodies indicating insulin therapy requirement and authoimmune fundaments of the disease, respectively. Copyright © 2016. Published by Elsevier Ltd.

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women.

PubMed

Ceresini, Graziano; Morganti, Simonetta; Rebecchi, Isabella; Bertone, Luca; Ceda, Gian Paolo; Bacchi-Modena, Alberto; Sgarabotto, Mariapaola; Baldini, Monica; Ablondi, Fabrizio; Valenti, Giorgio; Braverman, Lewis E

2004-01-01

Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism.

PubMed

Comak, Elif; Koyun, Mustafa; Kiliçarslan-Akkaya, Bahar; Bircan, Iffet; Akman, Sema

2011-01-01

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.

Treatment of hypopituitarism in patients receiving antiepileptic drugs.

PubMed

Paragliola, Rosa Maria; Prete, Alessandro; Kaplan, Peter W; Corsello, Salvatore Maria; Salvatori, Roberto

2015-02-01

Evidence suggests that there may be drug interactions between antiepileptic drugs and hormonal therapies, which can present a challenge to endocrinologists dealing with patients who have both hypopituitarism and neurological diseases. Data are scarce for this subgroup of patients; however, data for the interaction of antiepileptic drugs with the pituitary axis have shown that chronic use of many antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations of sex hormones. Other antiepileptic drugs increase sex hormone-binding globulin, which reduces the bioactivity of testosterone and estradiol. Additionally, the combined oestrogen-progestagen contraceptive pill might decrease lamotrigine concentrations, which could worsen seizure control. Moreover, sex hormones and their metabolites can directly act on neuronal excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine can enhance the sensitivity of renal tubules, a reduction in desmopressin dose might be necessary in patients with central diabetes insipidus. Although the effects of antiepileptic drugs in central hypothyroidism have not yet been studied, substantial evidence indicates that several antiepileptic drugs can increase thyroid hormone metabolism. However, although it is reasonable to expect a need for a thyroxine dose increase with some antiepileptic drugs, the effect of excessive thyroxine in lowering seizure threshold should also be considered. There are no reports of significant interactions between antiepileptic drugs and the efficacy of human growth hormone therapy, and few data are available for the effects of second-generation antiepileptic drugs on hypopituitarism treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

PubMed Central

Lazarus, John; Brown, Rosalind S.; Daumerie, Chantal; Hubalewska-Dydejczyk, Alicja; Negro, Roberto; Vaidya, Bijay

2014-01-01

This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking. PMID:25114871

The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis.

PubMed

Schoeman, J P; Herrtage, M E

2007-12-01

This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone (ACTH), pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A 2nd blood sample was taken 1 hour later for serum post-ACTH cortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose < 3.3 mmol/l, n = 12); normoglycaemic dogs (glucose 3.3-5.5 mmol/l, n = 12); hyperglycaemic dogs (glucose > 5.5 mmol/l, n = 12). Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.

Estimating the Risks and Benefits of Implantable Cardioverter Defibrillator Generator Replacement: A Systematic Review.

PubMed

Lewis, Krystina B; Stacey, Dawn; Carroll, Sandra L; Boland, Laura; Sikora, Lindsey; Birnie, David

2016-07-01

Every 4-7 years an implantable cardioverter defibrillator (ICD) pulse generator must be replaced surgically. This procedure is not without risk. In some cases, the risk versus benefit ratio may be against replacement. We aimed to synthesize the evidence on risks, benefits, and costs related to ICD replacement. A systematic review was conducted using electronic databases from 2000 onward. Literature screening, quality appraisal, and data extraction were independently conducted by two reviewers. Outcomes included major and minor complications, ICD therapies, and costs, which were synthesized descriptively. Of 1,483 citations, 17 nonrandomized studies met criteria. Median rate of major complications was 4.05% (range 0.55-7.37%) and minor complications was 3.50% (range 0.36-7.37%). Without non-ICD control groups, the true risk reduction provided by the ICD following replacement is unknown. Following ICD replacement, annualized rate of appropriate ICD therapy was 10.52% (range 2.42-75.00%). Of these, patients without therapies during their first generator life and those no longer meeting ICD criteria received appropriate therapies at nontrivial rates. Rates of complications associated with ICD replacement are substantial. No study had nonreplacement groups, hence the true risk reduction provided by the ICD following replacement is unknown. Our analysis did not identify a subgroup at low risk of therapies following replacement. Shared discussions should occur with patients about the evidence, healthcare goals, risk tolerances, and feelings about life and death trade-offs to enable high-quality decisions about ICD replacement. ©2016 Wiley Periodicals, Inc.

Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

PubMed

Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

2016-02-01

Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

PubMed Central

Bauer, Seth R.; Salem, Charbel; Connor, Michael J.; Groszek, Joseph; Taylor, Maria E.; Wei, Peilin; Tolwani, Ashita J.

2012-01-01

Summary Background and objectives Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions. Design, setting, participants, & measurements A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters. Results Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h−1, intraquartile range=0.052 h−1) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered. Conclusions There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy. PMID:22282479

Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989)

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

Meric, S.M.; Rubin, S.I.

The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi ofmore » 131I was determined to be an effective treatment for feline hyperthyroidism.« less

Risks and safety of combination therapy for hypothyroidism.

PubMed

Jonklaas, Jacqueline

2016-08-01

Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

The effect of physiotherapy in addition to testosterone replacement therapy on the efficiency of the motor system in men with hypogonadism.

PubMed

Bacevičienė, Rasa; Valonytė, Laura; Ceponis, Jonas

2013-01-01

The aim of this study was to analyze whether the addition of physiotherapy to testosterone replacement therapy provides added benefit in improving functional capacity of the motor system in men with hypogonadism. The study involved 3 groups of subjects: group 1, healthy men (n=20); group 2, men with hypogonadism who underwent testosterone replacement therapy with physiotherapy (TRT+PT) (n=8); and group 3, men with hypogonadism who underwent testosterone replacement therapy alone (TRT) (n=10). Physical activity (International Physical Activity Questionnaire [IPAQ]) and body composition (X-SCAN analysis) were analyzed; the vertical jump test (Leonardo Mechanography®) was applied. The application of testosterone replacement therapy together with physiotherapy for 6 months significantly increased the maximum and relative power of jump in the subjects in the TRT+PT group; however, in the TRT group, no statistically significant difference was observed. The maximum jump height for the subjects in the TRT+PT group significantly increased 6 months after the intervention; however, in the TRT group, this index remained unaltered. The lean body mass of the subjects in the TRT+PT group increased (P<0.05); however, in the TRT group, it did not change. The relative fat body mass in the TRT+PT group decreased significantly (P<0.05), but, in the TRT group, it had a tendency to increase, though insignificantly. Our results suggest that the application of testosterone replacement therapy together with physiotherapy (1 hour twice weekly) in men with hypogonadism may lead to earlier and better results in comparison with testosterone replacement therapy applied alone.

Dynamics of plasma proteome during leptin-replacement therapy in genetically based leptin deficiency.

PubMed

Andreev, V P; Dwivedi, R C; Paz-Filho, G; Krokhin, O V; Wong, M-L; Wilkins, J A; Licinio, J

2011-06-01

The effects of leptin-replacement therapy on the plasma proteome of three unique adults with genetically based leptin deficiency were studied longitudinally during the course of recombinant human leptin-replacement treatment. Quantitative proteomics analysis was performed in plasma samples collected during four stages: before leptin treatment was initiated, after 1.5 and 6 years of leptin-replacement treatment, and after 7 weeks of temporary interruption of leptin-replacement therapy. Of 500 proteins reliably identified and quantitated in those four stages, about 100 were differentially abundant twofold or more in one or more stages. Synchronous dynamics of abundances of about 90 proteins was observed reflecting both short- and long-term effects of leptin-replacement therapy. Pathways and processes enriched with overabundant synchronous proteins were cell adhesion, cytoskeleton remodeling, cell cycle, blood coagulation, glycolysis, and gluconeogenesis. Plausible common regulators of the above synchronous proteins were identified using transcription regulation network analysis. The generated network included two transcription factors (c-Myc and androgen receptor) that are known to activate each other through a double-positive feedback loop, which may represent a potential molecular mechanism for the long-term effects of leptin-replacement therapy. Our findings may help to elucidate the effects of leptin on insulin resistance.

How perceived feelings of "wellness" influence the decision-making of people with predialysis chronic kidney disease.

PubMed

Campbell-Crofts, Sandra; Stewart, Glenn

2018-04-01

To identify the subjective meanings attached to decisions made by people living with chronic kidney disease as they consider their transition to renal replacement therapy. Within the challenging world of chronic illness, people draw upon their temporal life experiences to help them make the best or most balanced primary healthcare decisions. Understanding the risks and benefits associated with these decisions has been an area of intense interest in health research. An exploratory qualitative descriptive design. A convenience sample of twelve people, at stages 3B to 5 of chronic kidney disease, attending two predialysis renal clinics in Sydney, Australia, consented to be interviewed. The semi-structured interviews centred on their decision-making experiences as they considered their transition to renal replacement therapy. Three themes emerged from participant narratives which have been framed into the following questions: (i) Do I need renal replacement therapy? (ii) What is the "right" renal replacement therapy for me? and (iii) When should I start renal replacement therapy? Decisions about the transition to renal replacement therapy were impacted upon by the participants' perceived feelings of wellness and the belief that renal replacement therapy would not be needed at any time in the foreseeable future. This study highlights the importance of optimising person-centred care and raises important issues for the education and management of people with chronic kidney disease in the predialysis stages of the illness. In order to facilitate the transition to renal replacement therapy, renal clinicians have a responsibility to more fully understand the patient journey during the predialysis stages of chronic kidney disease. A clearer understanding of patients' perceptions and decision-making experiences creates a space for mutual understanding. This is essential for the future development and implementation of collaborative, person-centred educational strategies and long-term renal healthcare outcomes. © 2017 John Wiley & Sons Ltd.

Association of Hypothyroidism with All-cause Mortality: A Cohort Study in an Older Adult Population.

PubMed

Huang, Huei-Kai; Wang, Jen-Hung; Kao, Sheng-Lun

2018-06-26

Although hypothyroidism is associated with many comorbidities, the evidence for its association with all-cause mortality in older adults is limited. To evaluate the association between hypothyroidism and all-cause mortality in older adults. Population-based retrospective cohort study. National Health Insurance Research Database in Taiwan. After 1:10 age/sex/index year matching, 2029 patients aged ≥65 years who received a new diagnosis of hypothyroidism between 2001 and 2011, and 20290 patients without hypothyroidism or other thyroid diseases, were included in the hypothyroidism and non-hypothyroidism cohorts respectively. All-cause mortality was defined as the primary outcome. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of mortality. To further evaluate the effect of thyroxine replacement therapy (TRT) on mortality, we divided patients with hypothyroidism into two groups: patients who received TRT and those who did not. Hypothyroidism was associated with an increased risk of all-cause mortality (adjusted HR [aHR] = 1.82, 95% confidence interval [CI] = 1.68-1.98, p < 0.001). Patients with hypothyroidism who received TRT had a lower risk of mortality than patients who did not receive TRT (aHR = 0.57, 95% CI = 0.49-0.66, p < 0.001). Similar results were obtained after further propensity score matching, in age-, sex-, and comorbidity-stratified analyses. Hypothyroidism was independently associated with increased all-cause mortality in older adults. In patients with hypothyroidism, TRT was associated with a lower risk of all-cause mortality.

Subclinical Hyperthyroidism: When to Consider Treatment.

PubMed

Donangelo, Ines; Suh, Se Young

2017-06-01

Subclinical hyperthyroidism is defined by a low or undetectable serum thyroid-stimulating hormone level, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (e.g., in Graves disease, toxic nodular goiter, or transient thyroiditis), by administration of thyroid hormone to treat malignant thyroid disease, or by unintentional excessive replacement therapy. The prevalence of subclinical hyperthyroidism in the general population is about 1% to 2%; however, it may be higher in iodinedeficient areas. The rate of progression to overt hyperthyroidism is higher in persons with thyroid-stimulating hormone levels less than 0.1 mIU per L than in persons with low but detectable thyroid-stimulating hormone levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and heart failure in older adults, increased cardiovascular and all-cause mortality, and decreased bone mineral density and increased bone fracture risk in postmenopausal women. However, the effectiveness of treatment in preventing these conditions is unclear. A possible association between subclinical hyperthyroidism and quality-of-life parameters and cognition is controversial. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for thyroid dysfunction in asymptomatic persons. The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating patients with thyroid-stimulating hormone levels less than 0.1 mIU per L if they are older than 65 years or have comorbidities such as heart disease or osteoporosis.

Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

PubMed

Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

2001-04-01

Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

Continuous renal replacement therapies: a brief primer for the neurointensivist.

PubMed

Patel, Pritesh; Nandwani, Veena; McCarthy, Paul J; Conrad, Steven A; Keith Scott, L

2010-10-01

Continuous renal replacement therapy (CRRT) is a renal replacement modality that is often used in the ICU setting, including the neuro-ICU. This form of renal replacement therapy has been used classically for acute renal failure in patients with hemodynamic compromise, but is gaining acceptance as a method to control vascular and extra-vascular volume and mediate cytokines in non-renal diseases. Although these uses are briefly discussed, this review concentrates on the different forms of continuous renal replacement, mainly focusing on the technology of convective versus diffusive modalities and briefly on filter technology. There is also discussion on the various anticoagulation regimes used in CRRT including data on performing CRRT without anticoagulation. This review is not meant to be a discussion on the pros and cons of CRRT versus intermittent dialysis, but rather a primer on the technology of CRRT and how this therapy may affect general care of the ICU patient.

The effectiveness of inpatient physical therapy compared to outpatient physical therapy in older adults after total hip replacement in the post-discharge period: a systematic review.

PubMed

Klugarova, Jitka; Klugar, Miloslav; Mareckova, Jana; Gallo, Jiri; Kelnarova, Zuzana

2016-01-01

Total hip replacement is the most effective and safest method for treating severe degenerative, traumatic and other diseases of the hip joint. Total hip replacement can reliably relieve pain and improve function in the majority of patients for a period of 15 to 20 years or more postoperatively. Physical therapy follows each total hip replacement surgery. Physical therapy protocols after total hip replacement in the post-discharge period vary widely in terms of setting (inpatient, outpatient), content (the particular set of exercises used), and frequency (e.g. daily versus twice a week). In current literature, there is no systematic review which has compared the effectiveness of inpatient and outpatient physical therapy in patients after total hip replacement in the post-discharge period. The objective of this systematic review was to compare the effectiveness of inpatient physical therapy with outpatient physical therapy on the quality of life and gait measures in older adults after total hip replacement in the post-discharge period. This review considered studies that include older adults (over 65 years) who have had total hip replacement and are in the post-discharge period. Adults with bilateral or multiple simultaneous surgeries and also patients who have had hemiarthroplasty of the hip joint were excluded.This review considered studies that included any type of physical therapy delivered in inpatient settings provided by professionals with education in physical therapy. Inpatient physical therapy delivered at any frequency and over any duration was included.This review considered studies that included as a comparator any type of physical therapy delivered in outpatient settings provided by professionals with education in physical therapy or no physical therapy.This review considered studies that included the following primary and secondary outcomes. The primary outcome was quality of life, assessed by any validated assessment tool. The secondary outcome was measures of gait assessed by any valid methods.This review considered both experimental and observational study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion. The search strategy aimed to find both published and unpublished studies. A three-step search strategy was utilized in 12 databases. Studies published in all languages and any date were considered for inclusion in this review. Assessment of methodological quality was not conducted as no studies were identified that met the inclusion criteria. Data extraction and synthesis was not performed because no studies were included in this systematic review. During to the three-step search strategy 4330 papers were identified. The primary and secondary reviewer independently retrieved 42 potentially relevant papers according to the inclusion criteria by title and abstract screening. Following assessment of full text all of the retrieved papers were excluded based on the inclusion criteria. There is no scientific evidence comparing the effectiveness of inpatient physical therapy with outpatient physical therapy in older patients after total hip replacement in the post-discharge period. This systematic review has identified gaps in the literature for comparing the effectiveness of inpatient physical therapy with and outpatient physical therapy on the quality of life and gait measures in older adults after total hip replacement in the post-discharge period. Prospective randomized double blind multicenter controlled trials are needed to answer this important clinical question.

Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

PubMed

Sanghi, Vedha; Kapoor, Aanchal

2016-01-01

Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy

PubMed Central

Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo; Rossi, Barbara; Ascione, Serena; Donati, Maria Alice; Morandi, Lucia Ovidia; Ravaglia, Sabrina; Pichiecchio, Anna; Ombrone, Daniela; Sacchini, Michele; Pasanisi, Maria Barbara; De Filippi, Paola; Danesino, Cesare; Della Casa, Roberto; Romano, Alfonso; Mollica, Carmine; Rosa, Margherita; Agovino, Teresa; Nusco, Edoardo; Porto, Caterina; Andria, Generoso

2014-01-01

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone. PMID:25052852

Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?

PubMed

Ip, David

2015-12-01

The current study evaluates whether the addition of low-level laser therapy into standard conventional physical therapy in elderly with bilateral symptomatic tri-compartmental knee arthritis can successfully postpone the need for joint replacement surgery. A prospective randomized cohort study of 100 consecutive unselected elderly patients with bilateral symptomatic knee arthritis with each knee randomized to receive either treatment protocol A consisting of conventional physical therapy or protocol B which is the same as protocol A with added low-level laser therapy. The mean follow-up was 6 years. Treatment failure was defined as breakthrough pain which necessitated joint replacement surgery. After a follow-up of 6 years, patients clearly benefited from treatment with protocol B as only one knee needed joint replacement surgery, while nine patients treated with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy should be incorporated into standard conservative treatment protocol for symptomatic knee arthritis.

Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

PubMed Central

Fervenza, Fernando C; Torra, Roser; Warnock, David G

2008-01-01

Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed. PMID:19707461

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

PubMed

Tumlin, James A; Murugan, Raghavan; Deane, Adam M; Ostermann, Marlies; Busse, Laurence W; Ham, Kealy R; Kashani, Kianoush; Szerlip, Harold M; Prowle, John R; Bihorac, Azra; Finkel, Kevin W; Zarbock, Alexander; Forni, Lui G; Lynch, Shannan J; Jensen, Jeff; Kroll, Stew; Chawla, Lakhmir S; Tidmarsh, George F; Bellomo, Rinaldo

2018-06-01

Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. ICUs. Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). IV angiotensin II or placebo. Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PubMed

van Varsseveld, N C; van Bunderen, C C; Franken, A A M; Koppeschaar, H P F; van der Lely, A J; Drent, M L

2016-08-01

The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

PubMed

Cintron, Dahima; Rodriguez-Gutierrez, Rene; Serrano, Valentina; Latortue-Albino, Paula; Erwin, Patricia J; Murad, Mohammad Hassan

2017-02-01

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

[Efficacy of iodine-131 in treating hyperthyroid heart disease].

PubMed

Song, Juan-Juan; Lin, Yan-Song; Zhu, Li; Li, Fang

2013-04-01

To investigate the value of iodine-131 therapy for hyperthyroidism complicated hyperthyroid heart disease(HHD) induced by Graves' disease or Plummer disease. Totally 40 HHD cases who were confirmed in our department from 2009 to 2010 were enrolled in this study. All patients received serum thyroid hormones and associated antibodies tests, 12-lead electrocardiogram, and/or thyroid imaging before and after iodine-131 therapy to access the treatment effectiveness. Among 31 patients with HHD due to Graves' disease and 9 due to Plummer disease, iodine-131 treatment resulted in euthyroidism in 15 and 5 patients and hypothyroid in 7 and 2 patients, while 9 and 2 remain hyperthyroid, respectively.Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were statistically significant(P<0.05) before and after iodine-131 therapy, while no significant difference for serum thyrotrophin receptor antibody, antithyroid peroxidase autoantibody, and anti-thyroglobulin antibody.Atrial fibrillation was the most common cardiac complication of hyperthyroidism(n=25, 62.5%) .The remission rate after iodine-131 treatment was 76.0%. Iodine-131 therapy can effectively and timely control hyperthyroid in HHD patients.

[Amiodarone-induced thyrotoxicosis].

PubMed

Bogazzi, Fausto; Tomisti, Luca; Di Bello, Vitantonio; Martino, Enio

2017-03-01

Amiodarone-induced thyroid dysfunction occurs in about 15-20% of patients under amiodarone therapy. Amiodarone-induced hypothyroidism (AIH) can develop in patients with an apparently normal thyroid gland or in those with an underlying chronic autoimmune thyroiditis. On a clinical ground, AIH is not challenging and can be easily treated with L-thyroxine therapy. Amiodarone-induced thyrotoxicosis (AIT) can occur in patients with (AIT 1) or without (AIT 2) an underlying thyroid disease. AIT 1 is a true iodine-induced hyperthyroidism occurring in patients with an underlying thyroid autonomy while AIT 2 is a drug-induced destructive thyroiditis. According to the different pathogenetic mechanism, AIT 2 is treated with glucocorticoids while AIT 1 usually responds to thionamides. Thyroidectomy should be considered when AIT represents an imminent risk for cardiac conditions, when patients require a prompt resolution of thyrotoxicosis or when they do not respond to the medical therapy. An effective collaboration between cardiologists and endocrinologists is crucial in each part of the management of AIT patients, including the evaluation of cardiological conditions with regard to thyroid hormone excess and whether, or not, it is necessary to continue amiodarone therapy.

[Rare differential diagnosis of hyperthyroidism].

PubMed

Besemer, Britta; Müssig, Karsten

2016-06-01

A 54-year-old female patient is admitted for evaluation of her thyroid function after two cycles of ipilimumab therapy. The decision for the anti-cytotoxic-T-lymphocyte-antigen-4-therapy (anti-CTLA-4) was made two months earlier because of malignant melanoma with pulmonary metastases. The patient was euthyroid before initiation of treatment and without known thyroid disease. The laboratory reveals thyrotoxicosis with elevated anti-thyroid peroxidase and anti-thyroglobulin antibody levels. The anti-thyroid stimulating hormone receptor antibody levels are within the normal range. Thyroid ultrasound shows a normal-sized, inhomogenous, hypoechogenic thyroid gland, consistent with autoimmune thyroiditis. Diagnosis of hyperthyroidism due to ipilimumab-induced autoimmune thyroiditis is made. The patient does not receive any thyroid-specific medication, with regular control of the thyroid hormone levels. When the patient becomes euthyroid, the ipilimumab therapy is continued. Three weeks later, the patient develops hypothyroidism and a supplementation with L-thyroxine is initiated. An anti-CTLA-4 therapy may cause thyroid dysfunction. Therefore, before initiation and in the course of the treatment, regular controls of the thyroid hormone levels are required. © Georg Thieme Verlag KG Stuttgart · New York.

Progesterone

MedlinePlus

... is used as a part of hormone replacement therapy in women who have passed menopause (the change ... hysterectomy (surgery to remove the uterus). Hormone replacement therapy usually includes estrogen, which is used to treat ...

Thyroxine revisited.

PubMed

Katrusiak, Andrzej; Katrusiak, Anna

2004-12-01

The crystal structure of the common therapeutic agent, the pentahydrated sodium salt of L-thyroxine hormone (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine), has been determined and discussed in relation to the drug's stability. The stoichiometry and absolute configuration (-)-C(8)S-[C15H10I4NO4]-.Na+.5H2O have been confirmed. The crystals are built of a three-dimensional supramolecular network with two symmetry-independent L-thyroxine anions, in two distinct conformations not previously reported, linked by strong NH-O hydrogen bonds into dimers. Two independent sodium cations are fivefold and sixfold coordinated. The cations and two independent water molecules not involved in coordinating the Na cations form sheets along the crystallographic (001) planes. The presence of differently coordinated cations and non-coordinating water molecules may be responsible for water transport and loss, for decay of the crystals, and subsequent low stability of the drug. Only a conglomerate could be obtained when racemic sodium thyroxine was crystallized from ethanol and methanol solutions by evaporation, which explains the equal penta-hydration of the sodium salts of enantiomorphic and racemic thyroxine, and the fact that there are no apparent differences in their stability. (c) 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Rapid Immunochromatographic Detection of Serum Anti-α-Galactosidase A Antibodies in Fabry Patients after Enzyme Replacement Therapy.

PubMed

Nakano, Sachie; Tsukimura, Takahiro; Togawa, Tadayasu; Ohashi, Toya; Kobayashi, Masahisa; Takayama, Katsuyoshi; Kobayashi, Yukuharu; Abiko, Hiroshi; Satou, Masatsugu; Nakahata, Tohru; Warnock, David G; Sakuraba, Hitoshi; Shibasaki, Futoshi

2015-01-01

We developed an immunochromatography-based assay for detecting antibodies against recombinant α-galactosidase A proteins in serum. The evaluation of 29 serum samples from Fabry patients, who had received enzyme replacement therapy with agalsidase alpha and/or agalsidase beta, was performed by means of this assay method, and the results clearly revealed that the patients exhibited the same level of antibodies against both agalsidase alpha and agalsidase beta, regardless of the species of recombinant α-galactosidase A used for enzyme replacement therapy. A conventional enzyme-linked immunosorbent assay supported the results. Considering these, enzyme replacement therapy with agalsidase alpha or agalsidase beta would generate antibodies against the common epitopes in both agalsidase alpha and agalsidase beta. Most of the patients who showed immunopositive reaction exhibited classic Fabry phenotype and harbored gene mutations affecting biosynthesis of α-galactosidase A. As immunochromatography is a handy and simple assay system which can be available at bedside, this assay method would be extremely useful for quick evaluation or first screening of serum antibodies against agalsidase alpha or agalsidase beta in Fabry disease with enzyme replacement therapy.

[Historical aspects and new formulations of levothyroxine sodium for hypothyroidism treatment].

PubMed

Shacham, Elena Chertok; Ishay, Avraham; Luboshitsky, Rafael

2013-09-01

At the end of the 19th century symptoms and signs of hypothyroidism were described in the medical literature. At that time myxedema was a main clinical presentation of the hypothyroid patient. Today, the diagnosis of hypothyroidism is determined mainly by laboratory evaluation with most patients exhibiting only a few clinical signs of thyroid dysfunction. The treatment of hypothyroidism has progressed from partially purified extracts of bovine thyroid gland to an oral administration of synthetic hormone. Since 1981 the only thyroid hormone replacement drug approved by the Israeli Ministry of Health was the Eltroxin brand, made by GlaxoSmithKline. Levothyroxine has a narrow therapeutic range, thus a potential variance exists in the therapeutic efficacy among different levothyroxine preparations. In 2007 the Food and Drugs Administration (FDA) announced that the difference in potency of various levothyroxine brands should not exceed ten percent. In 2007 the GSK Company moved the manufacturing of Eltroxin from Canada to Germany. This resulted in a change of the inert ingredients of the drug. It is of interest to know that since the arrival of the new thyroxine formulation in the Israeli pharmaceutical market there has been a dramatic increase in reports of adverse reactions. The media coverage of adverse effects associated with Eltroxin became widespread in television, newspapers and internet sites. This led to a burden on the healthcare system, manifesting itself by an increase in thyroid blood tests, physician follow-up visits, as well as the importing and distribution of a new brand of thyroxine.

Hyperthyroidism in an infant of a mother with autoimmune hypothyroidism with positive TSH receptor antibodies.

PubMed

Joshi, Kriti; Zacharin, Margaret

2018-04-25

Neonatal hyperthyroidism is rare, seen in infants of mothers with Graves' disease (GD), with transplacental transfer of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs). We describe a neonate with severe hyperthyroidism due to TRAbs, born to a mother with autoimmune hypothyroidism. A baby boy born preterm at 35 weeks had irritability, tachycardia and proptosis after birth. The mother had autoimmune hypothyroidism, from age 10, with thyroxine replacement and normal thyroid function throughout her pregnancy. She had never been thyrotoxic. There was a family history of Hashimoto's thyroiditis (HT) and GD. The baby's thyroid function on day 3 demonstrated gross thyrotoxicosis, TSH<0.01 mIU/L (normal range [NR]<10 mIU/L), free thyroxine (FT4)>77 pmol/L (20-35), free triiodothyronine (FT3) 15.4 pmol/L (4.2-8.3) and TRAb 18.4 IU/L (<1.8). The mother's TRAb was 24.7 IU/L. Thyrotoxicosis required propranolol and carbimazole (CBZ). Thyroid function normalized within 10 days. The baby was weaned off medication by 7 weeks. He remains euthyroid. We postulate that this mother had co-existing destructive thyroiditis and thyroid-stimulating antibodies (TSAbs) and TSHR blocking antibodies (TBAb), rendering her unable to raise a thyrotoxic response to the TSAbs but with predominant TSAb transmission to her infant. Maternal history of any thyroid disorder may increase the risk of transmission to an infant, requiring a careful clinical assessment of the neonate, with important implications for future pregnancies.

Increased Requirement of Replacement Doses of Levothyroxine Caused by Liver Cirrhosis.

PubMed

Benvenga, Salvatore; Capodicasa, Giovanni; Perelli, Sarah; Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro

2018-01-01

Since hypothyroidism is a fairly common dysfunction, levothyroxine (L-T4) is one of the most prescribed medications. Approximately 70% of the administered L-T4 dose is absorbed. The absorption process takes place in the small intestine. Some disorders of the digestive system and some medicines, supplements, and drinks cause L-T4 malabsorption, resulting in failure of serum TSH to be normal. Only rarely liver cirrhosis is mentioned as causing L-T4 malabsorption. In this study, we report increased requirement of daily doses of l-thyroxine in two patients with the atrophic variant of Hashimoto's thyroiditis and liver cirrhosis. In one patient, this increased requirement could have been contributed by the increased serum levels of the estrogen-dependent thyroxine-binding globulin (TBG), which is the major plasma carrier of thyroid hormones. In the other patient, we switched from tablet L-T4 to liquid L-T4 at the same daily dose. Normalization of TSH levels was achieved, but TSH increased again when she returned to tablet L-T4. Liver cirrhosis can cause increased L-T4 requirements. In addition to impaired bile secretion, the mechanism could be increased serum TBG. A similar increased requirement of L-T4 is observed in other situations characterized by elevation of serum TBG. Because of better intestinal absorption, L-T4 oral liquid formulation is able to circumvent the increased need of L-T4 in these patients.

Medication Guide

MedlinePlus

... before starting any new medication. First-Line Medications: Nicotine Replacement Therapy (NRT) These medications are called "first- ... they might try a "second-line" medication instead. Nicotine replacement therapy (NRT) helps smokers quit by reducing ...

Thyroid hormones determine developmental mode in sand dollars (Echinodermata: Echinoidea).

PubMed

Heyland, Andreas; Reitzel, Adam M; Hodin, Jason

2004-01-01

Evolutionary transitions in larval nutritional mode have occurred on numerous occasions independently in many marine invertebrate phyla. Although the evolutionary transition from feeding to nonfeeding development has received considerable attention through both experimental and theoretical studies, mechanisms underlying the change in life history remain poorly understood. Facultative feeding larvae (larvae that can feed but will complete metamorphosis without food) presumably represent an intermediate developmental mode between obligate feeding and nonfeeding. Here we show that an obligatorily feeding larva can be transformed into a facultative feeding larva when exposed to the thyroid hormone thyroxine. We report that larvae of the subtropical sand dollar Leodia sexiesperforata (Echinodermata: Echinoidea) completed metamorphosis without exogenous food when treated with thyroxine, whereas the starved controls (no thyroxine added) did not. Leodia sexiesperforata juveniles from the thyroxine treatment were viable after metamorphosis but were significantly smaller and contained less energy than sibling juveniles reared with exogenous food. In a second starvation experiment, using an L. sexiesperforata female whose eggs were substantially larger than in the first experiment (202+/-5 vs. 187+/-5 microm), a small percentage of starved L. sexiesperforata larvae completed metamorphosis in the absence of food. Still, thyroxine-treated larvae in this experiment completed metamorphosis faster and in much higher numbers than in the starved controls. Furthermore, starved larvae of the sand dollar Mellita tenuis, which developed from much smaller eggs (100+/-2 microm), did not complete metamorphosis either with or without excess thyroxine. Based on these data, and from recent experiments with other echinoids, we hypothesize that thyroxine plays a major role in echinoderm metamorphosis and the evolution of life history transitions in this group. We discuss our results in the context of current life history models for marine invertebrates, emphasizing the role of egg size, juvenile size, and endogenous hormone production for the evolution of nonfeeding larval development.

Studies on the Induction of Bone and Soft Tissue Tumours in Rats by Gamma Irradiation and the Effect of Growth Hormone and Thyroxine

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

Cater, D. B.; Baserga, R.; Lisco, H.

1959-06-01

A single dose of 3000 roentgen of gamma irradiation from a iridium-192 teletherapy source applied to both knee joints of growing female rats induced osteosarcomata in 34 out of 116 rats. Fifty rats developed sarcomata of soft tissues, 10 cancer of the skin, and 12 had mammary cancers. Eighty days after irradiation, ten-week courses of growth hormone, thyroxine, growth hormone followed by thyroxine, and saline were given to study the effect of hormone treatment on the incidence and induction period of radiationinduced bone sarcomata. Twelve out of 30 growthhormone-treated rats developed bone sarcomata compared with 7 out of 31 inmore » the saline injected group. Thyroxine treatment significantly reduced the mean latent period of radiation-induced osteosarcomata. The incidence of other types of malignant tumors was not affected by the hormone treatments.« less

[Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

PubMed

Vyshnevs'ka, O A; Bol'shova, O V

2013-06-01

Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa.

PubMed

Tsai, Yi-Ting; Wu, Wen-Hsuan; Lee, Ting-Ting; Wu, Wei-Pu; Xu, Christine L; Park, Karen S; Cui, Xuan; Justus, Sally; Lin, Chyuan-Sheng; Jauregui, Ruben; Su, Pei-Yin; Tsang, Stephen H

2018-05-05

To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO). Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. This study included 2 kinds of human RHO mutation knock-in mouse models: Rho P23H and Rho D190N . In total, 23 Rho P23H/P23H , 43 Rho P23H/+ , and 31 Rho D190N/+ mice were used for analysis. This study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA. Electroretinographic and histologic analysis. The thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both Rho P23H and Rho D190N disease models were preserved more significantly using ablate-and-replace gene therapy (P < 0.001), but not by gene replacement monotherapy. As a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Thyroxine treatment may be useful for subclinical hypothyroidism in patients with female infertility.

PubMed

Yoshioka, Waka; Amino, Nobuyuki; Ide, Akane; Kang, Shino; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Nakamura, Hirotoshi; Miyauchi, Akira

2015-01-01

Infertile women sometimes associated with subclinical hypothyroidism (SCH). The guidelines of the American Endocrine Society, and American Association of Clinical Endocrinologists and American Thyroid Association recommend treatment with thyroxine (T4) for patients with SCH who want to have children. We examined 69 female infertile patients with SCH and the effects of levothyroxine (l-T4) therapy on pregnancy rates and pregnancy outcomes were observed. Fifty-eight (84.1%) patients successfully conceived during the T4 treatment period (Group A), although 17 patients (29.3%) had miscarriage afterward. The remaining 11 patients continued to be infertile (Group B). The median TSH value in Group A before the T4 treatment was 5.46 μIU/mL (range 3.1-13.3) and this significantly decreased to 1.25 μIU/mL (range 0.02-3.75) during the treatment (p<0.001). The estimated duration of infertility before the T4 treatment was 2.8±1.7 years and the duration until pregnancy after the treatment was significantly shorter at 0.9±0.9 years (p<0.001). Shortening of the infertile period after the T4 therapy was observed not only in patients who were treated with assisted reproductive technology (ART) but also in patients who conceived spontaneously in Group A. Administered T4 dose was 54.3±14.2 μg before pregnancy and 68.5±22.8 μg during pregnancy (p<0.001). Anti-thyroid autoantibodies were identified in 42.0% of all patients and no significant difference was observed in positivity between Group A and Group B. High successful pregnancy rate and shorter duration of infertility until pregnancy after T4 treatment strongly suggest that T4 enhanced fertility in infertile patients with SCH.

Recurrent Graves' hyperthyroidism after prolonged radioiodine-induced hypothyroidism.

PubMed

Salman, Fariha; Oktaei, Hooman; Solomon, Solomon; Nyenwe, Ebenezer

2017-07-01

Radioactive iodine (RAI) is the most cost effective therapy for Graves' disease (GD). Patients with GD who have become hypothyroid after therapeutic RAI, rarely develop recurrence of disease. Herein we describe a case of recurrence of thyrotoxicosis after 2 years of hypothyroidism. We present the clinical features, laboratory findings, imaging and management of an unusual case of recurrent hyperthyroidism. A 48-year-old male presented to the emergency room with a 2-day history of palpitation, chest discomfort and 30 pounds of weight loss. Examination was remarkable for rapid and irregular pulse, diffuse thyromegaly and brisk deep tendon reflexes but no eye changes or tremors. Laboratory tests showed thyroid-stimulating hormone (TSH) of <0.004 (0.3-5.6 mIU/ml), free thyroxine (FT4) 4.96 (0.9-1.8 ng/dl), free triiodothyronine (FT3) >20 (1.8-4.7 pg/ml), total thyroxine >800 (80-200 ng/dl). Electrocardiogram showed atrial fibrillation with rapid ventricular response. RAI uptake and scan showed a homogenous gland with 54% uptake in 6 h and 45% in 24 h. He was treated with propranolol and propylthiouracil with some clinical improvement. He subsequently underwent RAI therapy and developed hypothyroidism after 8 weeks. Hypothyroidism was treated with levothyroxine. At 2 years after RAI ablation, he again developed symptoms of hyperthyroidism and had suppressed TSH. The levothyroxine dose was stopped, 3 weeks after discontinuing levothyroxine, he remained hyperthyroid with TSH of 0.008 and FT4 of 1.62 and FT3 of 4.8. RAI uptake demonstrated 17% uptake at 24 h. Recurrent hyperthyroidism in GD is uncommon after development of post-ablative hypothyroidism. Our case illustrates the need for continued surveillance.

The site-specific basicity of thyroid hormones and their precursors as regulators of their biological functions.

PubMed

Tóth, Gergo; Hosztafi, Sándor; Kovács, Zsuzsanna; Noszál, Béla

2012-03-05

The complete macro- and microequilibrium analyses of thyroxine, liothyronine, reverse liothyronine and their biological precursors--diiodotyrosine, monoiodotyrosine and tyrosine are presented. Their biosyntheses, receptor- and transport protein-binding are shown to be distinctively dependent on the phenolate basicity. The protonation macroconstants were determined by (1)H NMR-pH and/or UV-pH titrations. Microconstants of the minor microspecies were determined by deductive methods, in which O-methylated and carboxymethylated derivatives were synthesized, and the combination of their NMR-pH and UV-pH titration provided the experimental base to evaluate all the microconstants. NMR-pH profiles, macro-, and microscopic protonation schemes, and species-specific diagrams are included. Biosyntheses of the thyroid hormones take place by oxidative coupling of two iodotyrosine residues catalyzed by thyreoperoxidase in thyreoglobulin. On the grounds of our phenolate microconstants of precursors the thyroxine over liothyronine ratio needs to be 9:1 after their biosynthesis in thyroid gland, which is in good agreement with biochemical data. The microconstants show that the phenolates are in proton donor (-OH) form in liothyronine whereas they occur in proton acceptor (-O(-)) form in thyroxine at the pH of blood. These facts explain several facts that have previously been empirically known: the affinity of liothyronine for the receptor is higher than that of thyroxine, the affinity of thyroxine for the transport proteins is higher than that of liothyronine and the selectivity of thyroxine for the OATP1C1 organic anion transporter is higher than that of liothyronine. Copyright © 2011 Elsevier B.V. All rights reserved.

Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea.

PubMed

Schoeman, Johan P; Goddard, Amelia; Herrtage, Michael E

2007-11-15

To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine. Prospective case-control study. 57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies. Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge. Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3. High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.

Effect of L-thyroxine treatment on peripheral blood dendritic cell subpopulations in patients with Hashimoto's thyroiditis.

PubMed

Stasiolek, Mariusz; Dedecjus, Marek; Adamczewski, Zbigniew; Sliwka, Przemyslaw Wiktor; Brzezinski, Jan; Lewinski, Andrzej

2014-01-01

Recent reports suggested dendritic cells (DCs) to be important players in the pathogenesis of autoimmune thyroid processes in humans. However, there are virtually no data addressing the influence of thyroid autoaggression-associated disturbances of thyrometabolic conditions on DCs biology. The aim of the study was to evaluate the influence of L-thyroxine supplementation on conventional and plasmacytoid peripheral blood DCs subtypes in patients with hypothyroidism due to Hashimoto's thyroiditis (HT). Eighteen patients with newly diagnosed hypothyroidism due to HT were included into the study. All patients received L-thyroxine treatment with doses adjusted to reach euthyroidism. Peripheral blood DC subtypes structure and immunoregulatory phenotype were analyzed by flow cytometry in the same patient prospectively at two time points: (i) before and (ii) 3 months after beginning of L-thyroxine treatment (hypothyroidism vs. euthyroidism, respectively). Percentage of plasmacytoid DCs in peripheral blood mononuclear cells fraction was significantly decreased in the course of L-thyroxine treatment (0.27 ± 0.19 vs. 0.11 ± 0.08; p < 0.05), whereas we did not observe any changes in the number of conventional DCs. However, the phenotypic analysis showed a significant increase of conventional DCs expressing CD86 and CD91 (64.25 ± 21.6% vs. 86.3 ± 11%; p < 0.05 and 30.75 ± 11.66% vs. 44.5 ± 13.3%; p < 0.05; respectively) in euthyroid patients. Standard L-thyroxine supplementation in HT patients exerted significant immunoregulatory effects, associated with quantitative and phenotypic changes of peripheral blood DC subpopulations.

Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults.

PubMed

Oerbeck, Beate; Sundet, Kjetil; Kase, Bengt F; Heyerdahl, Sonja

2003-10-01

To describe intellectual, motor, and school-associated outcome in young adults with early treated congenital hypothyroidism (CH) and to study the association between long-term outcome and CH variables acting at different points in time during early development (CH severity and early L-thyroxine treatment levels [0-6 years]). Neuropsychological tests were administered to all 49 subjects with CH identified during the first 3 years of the Norwegian neonatal screening program (1979-1981) at a mean age of 20 years and to 41 sibling control subjects (mean age: 21 years). The CH group attained significantly lower scores than control subjects on intellectual, motor, and school-associated tests (total IQ: 102.4 [standard deviation: 13] vs 111.4 [standard deviation: 13]). Twelve (24%) of the 49 CH subjects had not completed senior high school, in contrast to 6% of the control subjects. CH severity (pretreatment serum thyroxine [T4]) correlated primarily with motor tests, whereas early L-thyroxine treatment levels were related to verbal IQ and school-associated tests. In multiple regression analysis, initial L-thyroxine dose (beta = 0.32) and mean serum T4 level during the second year (beta = 0.48) predicted Verbal IQ, whereas mean serum T4 level during the second year (beta = 0.44) predicted Arithmetic. Long-term outcome revealed enduring cognitive and motor deficits in young adults with CH relative to control subjects. Verbal functions and Arithmetic were associated with L-thyroxine treatment variables, suggesting that more optimal treatment might be possible. Motor outcome was associated with CH severity, indicating a prenatal effect.

Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

EPA Science Inventory

Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Renal replacement therapy in patients with severe precapillary pulmonary hypertension with acute right heart failure.

PubMed

Sztrymf, Benjamin; Prat, Dominique; Jacobs, Frédéric M; Brivet, François G; O'Callaghan, Dermot S; Price, Laura C; Jais, Xavier; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc

2013-01-01

Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined. Copyright © 2012 S. Karger AG, Basel.

Uterine Development After Estrogen Replacement Therapy in Women with Different Etiologies of Primary Hypogonadism.

PubMed

Kim, Hyo Jeong; Lee, Dong-Yun; Yoon, Byung-Koo; Choi, DooSeok

2016-08-01

To evaluate uterine development with estrogen replacement therapy in patients with primary amenorrhea due to hypogonadism. Retrospective study. Thirty-five women. Women who were younger than 20 years of age and who had primary amenorrhea and an immaturely shaped uterus were included. Changes in uterine cross-sectional area (UXA) and uterine maturity in pelvic ultrasound after 2 year of estrogen replacement therapy were assessed on the basis of the etiology of primary hypogonadism. Patients were classified into three groups according to the etiology of primary hypogonadism: Turner syndrome (n = 19), hypogonadotropic hypogonadism after brain surgery (n = 10), and premature ovarian insufficiency after cancer treatment (n = 6). Overall, the mean UXA significantly increased (from 3.1 ± 1.8 to 11.6 ± 4.9 cm(2)) after estrogen replacement therapy (P < .001), but the final UXA was significantly smaller in patients with premature ovarian insufficiency compared with other etiologies. In logistic regression analysis, etiology and the cumulative dose of estrogen were associated with uterine maturation (P = .011 and .004, respectively). Estrogen replacement therapy induced growth of the uterus in patients with primary hypogonadism. However, the response to estrogen replacement therapy varied on the basis of the total cumulative dose of estrogen and etiology of primary hypogonadism. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Monitoring Thyroid Function in Patients on Levothyroxine. Assessment of Conformity to National Guidance and Variability in Practice.

PubMed

Scargill, Jonathan J; Livingston, Mark; Holland, David; Duff, Christopher J; Fryer, Anthony A; Heald, Adrian H

2017-10-01

With demand for endocrine tests steadily increasing year-on-year, we examined thyroid function test (TFT) frequencies in patients on levothyroxine replacement therapy to assess the effect of initial TFT results and request source on TFT re-testing interval. All TFTs performed by the Clinical Biochemistry Departments at the Salford Royal Hospital (2009-2012; 288 263 requests from 139 793 patients) and University Hospital of North Midlands (2011-2014; 579 156 requests from 193 035 patients) were extracted from the laboratory computer systems. Of these, 54 894 tests were on 13 297 patients confirmed to be on levothyroxine therapy in the test cohort (Salford) and 67 298 requests on 11 971 patients in the confirmatory cohort (North Midlands). In the test cohort, median TFT re-testing interval in the total group was 19.1 weeks (IQR 9.1-37.7 weeks), with clearly defined peaks in TFT re-testing evident at 6 and 12 months and a prominent broad peak at 1-3 months. Median re-test interval was much lower than recommended (52 weeks) for those with normal TFTs at 31.3 weeks (30.6 weeks for the confirmatory cohort). Where thyroid-stimulating hormone (TSH) was elevated and free thyroxine (fT4) was below the reference range, re-test interval was much longer than is recommended (8 weeks) at 13.4-17.6 weeks (7.1-23.4 weeks in the confirmatory cohort), as was the interval when TSH was below and fT4 was above the normal range, at 16.7-25.6 weeks (27.5-31.9 weeks in the confirmatory cohort). Our findings show that the majority of TFT requests are requested outside recommended intervals and within-practice variability is high. A new approach to ensuring optimum monitoring frequency is required. Direct requesting from the clinical laboratory may provide one such solution. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluating Nicotine Replacement Therapy and Stage-Based Therapies in a Population-Based Effectiveness Trial

ERIC Educational Resources Information Center

Velicer, Wayne F.; Friedman, Robert H.; Fava, Joseph L.; Gulliver, Suzy B.; Keller, Stefan; Sun, Xiaowu; Ramelson, Harley; Prochaska, James O.

2006-01-01

Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England…

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

PubMed

Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein; Holman, Rebecca; Baiko, Sergey; Baskın, Esra; Bjerre, Anna; Cloarec, Sylvie; Cornelissen, Elisabeth A M; Espinosa, Laura; Heaf, James; Stone, Rosário; Shtiza, Diamant; Zagozdzon, Ilona; Harambat, Jérôme; Jager, Kitty J; Groothoff, Jaap W; van Stralen, Karlijn J

2017-05-27

We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities. ERA-EDTA and ESPN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low Treatment Adherence in Pubertal Children Treated with Thyroxin or Growth Hormone.

PubMed

Lass, Nina; Reinehr, Thomas

2015-01-01

Treatment outcome depends largely on treatment adherence (TA). However, studies analyzing TA in chronic endocrine diseases are scarce and controversial in childhood. We studied TA in 103 children treated subcutaneously with growth hormone (GH) and 97 children treated orally with thyroxin. TA was calculated based on the prescription refill rates. The number of GH injections was recorded by an autoinjector device in 23 children treated with GH. The correlation between recorded TA and calculated TA based on prescription refill rates was very good (p < 0.001, r = 0.83). TA was lower (p < 0.01) in pubertal children compared to prepubertal children and in children self-administering their medication compared to those whose drug was administered by their parents, both in GH- and thyroxin-treated children. Overall, 67% of the pubertal children treated with GH and 58% of the pubertal children treated with thyroxin missed at least 1 dose per week. TA was higher (p < 0.001) in children with thyroxin treatment compared to children treated with recombinant human GH (8 vs. 26% missed >3 doses/week). Puberty and self-administration of drugs were negative predictors of TA. Therefore, in puberty, prevention and treatment efforts should be undertaken to improve TA, especially when adolescents administer their drugs themselves. © 2015 S. Karger AG, Basel.

Rapid Immunochromatographic Detection of Serum Anti-α-Galactosidase A Antibodies in Fabry Patients after Enzyme Replacement Therapy

PubMed Central

Nakano, Sachie; Tsukimura, Takahiro; Togawa, Tadayasu; Ohashi, Toya; Kobayashi, Masahisa; Takayama, Katsuyoshi; Kobayashi, Yukuharu; Abiko, Hiroshi; Satou, Masatsugu; Nakahata, Tohru; Warnock, David G.; Sakuraba, Hitoshi; Shibasaki, Futoshi

2015-01-01

We developed an immunochromatography-based assay for detecting antibodies against recombinant α-galactosidase A proteins in serum. The evaluation of 29 serum samples from Fabry patients, who had received enzyme replacement therapy with agalsidase alpha and/or agalsidase beta, was performed by means of this assay method, and the results clearly revealed that the patients exhibited the same level of antibodies against both agalsidase alpha and agalsidase beta, regardless of the species of recombinant α-galactosidase A used for enzyme replacement therapy. A conventional enzyme-linked immunosorbent assay supported the results. Considering these, enzyme replacement therapy with agalsidase alpha or agalsidase beta would generate antibodies against the common epitopes in both agalsidase alpha and agalsidase beta. Most of the patients who showed immunopositive reaction exhibited classic Fabry phenotype and harbored gene mutations affecting biosynthesis of α-galactosidase A. As immunochromatography is a handy and simple assay system which can be available at bedside, this assay method would be extremely useful for quick evaluation or first screening of serum antibodies against agalsidase alpha or agalsidase beta in Fabry disease with enzyme replacement therapy. PMID:26083343

Dispelling Myths about Nicotine Replacement Therapy

MedlinePlus

... of nicotine gum is associated with hyperinsulinemia and insulin resistance. Circulation. 1996;94:878-881. 16. Epifano L, ... R, Shafer Z, Fainaru M. Weight gain and insulin resistance during nicotine replacement therapy. Clin Cardiol. 1999;22: ...

Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism.

PubMed

Squarza, S; Rossi, U G; Torcia, P; Cariati, M

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones. The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Exogenous thyrotoxicosis in dogs attributable to consumption of all-meat commercial dog food or treats containing excessive thyroid hormone: 14 cases (2008-2013).

PubMed

Broome, Michael R; Peterson, Mark E; Kemppainen, Robert J; Parker, Valerie J; Richter, Keith P

2015-01-01

To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone. Retrospective and prospective case series. 14 dogs. Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples. Total serum thyroxine concentrations were high (median, 8.8 μg/dL; range, 4.65 to 17.4 μg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 μg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 μg of thyroxine/g. Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.

GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution.

PubMed

Brignardello, E; Felicetti, F; Castiglione, A; Fortunati, N; Matarazzo, P; Biasin, E; Sacerdote, C; Ricardi, U; Fagioli, F; Corrias, A; Arvat, E

2015-02-01

Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD. Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont. GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development. In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism.

PubMed

Silfen, M E; Garvin, J H; Hays, A P; Starkman, H S; Aranoff, G S; Levine, L S; Feldstein, N A; Wong, B; Oberfield, S E

2001-02-01

We report a 15-year-old boy who had isolated central diabetes insipidus initially diagnosed at age 11 years. A brain magnetic resonance imaging (MRI) was normal at the time. At age 12 years, growth hormone (GH) testing was performed because of a decline in linear growth rate and demonstrated GH deficiency. After a repeat normal brain MRI, GH therapy was begun. Three years later, hormonal testing revealed prepubertal gonadotropins and low testosterone levels, free thyroxine index, and morning cortisol levels. Repeat brain MRI demonstrated a 9-mm enhancing lesion in the region of the pituitary stalk. The pathologic diagnosis was that of a high-grade malignant B-cell lymphoma, suggestive of Burkitt Lymphoma. Growth hormone therapy has not been associated with an increased incidence of lymphoma. This report underscores the need for vigilance in follow-up brain imaging and hormonal evaluation in children with diabetes insipidus, especially those with evolving anterior hormone deficiencies.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

PubMed

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer

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

Chan, D.W.; Waud, J.M.; Hsu, T.H.

1983-06-01

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T/sub 4/ derivative that does not bind significantly to the thyroxine-binding proteins. This RIA was evaluated for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T/sub 4/ assay was expressed as coefficient of variation. The correlation coefficients (r) of a dialysis method and a free thyroxine index were 0.871 and 0.911, respectively. Free T/sub 4/ correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition,more » 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T/sub 4/, very low T/sub 3/, and elevated rT/sub 3/. We found this free T/sub 4/ assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.« less

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

Euthyroid ''thyroxine toxicosis''

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

Mankikar, G.D.; Clark, A.N.

A survey was made of thyroid function tests on 1,153 patients screened for thyroid disease during a two-year period in a Geriatric Department; 13 percent of the test results fell outside the normal range. Of 88 patients who showed above-normal results, only 12 presented with clinical features of thyrotoxicosis. In 37 patients, the biochemical findings indicated euthyroid ''thyroxine toxicosis''; high values were found for serum thyroxine (T4) and the free thyroxine index (FT4I) but there were no clinical signs or symptoms of thyrotoxicosis; the values reverted to normal within one to three weeks. This pattern was seen also in 7more » examples of T4-treated hypothyroidism. (Overall, the test findings indicated 61 cases of hypothyroidism.) The significance of this transient increase in T4 and FT4I values is discussed. The false positive results suggest that, when laboratory findings are not compatible with the clinical signs, the thyroid function tests should be repeated after another two weeks.« less

In Vitro Metabolism of Thyroxine by Rat and Human Hepatocytes

EPA Science Inventory

The liver metabolizes thyroxine (T4) through two major pathways: deiodination and conjugation. Rodents utilize both pathways, but it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T4. The objective of this study was to compa...

Use of continuous renal replacement therapy in acute aluminum phosphide poisoning: a novel therapy.

PubMed

Nasa, Prashant; Gupta, Ankur; Mangal, Kishore; Nagrani, S K; Raina, Sanjay; Yadav, Rohit

2013-09-01

Aluminum phosphide is most common cause of poisoning in northern India. There is no specific antidote available and management of such cases is mainly supportive with high mortality. We present two cases of severe acute aluminium phosphide poisoning where continuous renal replacement therapy (CRRT) was started early along with other resuscitative measures and both the patients survived.

Lipid profiles in the untreated patients with Hashimoto thyroiditis and the effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto thyroiditis.

PubMed

Tagami, Tetsuya; Tamanaha, Tamiko; Shimazu, Satoko; Honda, Kyoko; Nanba, Kazutaka; Nomura, Hidenari; Yoriko, Sakane Ueda; Usui, Takeshi; Shimatsu, Akira; Naruse, Mitsuhide

2010-01-01

To evaluate the prevalence of dyslipidemia in the population of Hashimoto thyroiditis, we reviewed medical records on the consecutive 1181 cases with adult Hashimoto thyroiditis and 830 cases were adopted for the study. First, the serum TSH level increased and serum free T4 level decreased, slightly but significantly, with increasing age. There were significant positive correlations between serum TSH levels and lipid parameters such as total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C and LDL-C/HDL-C ratio (L/H). In contrast, there were significant negative correlations between serum free T4 levels and all of these lipid parameters. According to the thyroid function, the cases were classified into 4 groups such as thyrotoxicosis (TT), euthyroidism (EU), subclinical hypothyroidism (SH) and overt hypothyroidism (OH). TC, HDL-C, non-HDL-C and LDL-C of TT were significantly lower than those in EU. In contrast, TC, TG, non-HDL-C, LDL-C, L/H and age of OH were significantly higher than those in EU. Interestingly, LDL-C and L/H of SH were significantly higher compared with EU. Thirty-two of SH patients were treated with small doses of levothyroxine and the effects on the lipid profile were examined. The TC, non-HDL-C, LDL-C and L/H were significantly decreased after treatment. In conclusion, the prevalence of dyslipidemia increases along with hypofunction of the thyroid and T4 replacement therapy may improve lipid profile in the cases of SH with Hashimoto thyroiditis.

Laparoscopic Roux-en-Y gastric bypass surgery on morbidly obese patients with hypothyroidism.

PubMed

Fazylov, Rafael; Soto, Eliana; Cohen, Steve; Merola, Stephen

2008-06-01

It is well known that obesity is accompanied by changes in thyroid function. Hypothyroidism is associated with increased body weight. The aim of this study was to evaluate the operative outcomes, weight loss, and the effect of weight loss on thyroid function in morbidly obese patients with hypothyroidism who undergo laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. A retrospective review of 20 morbidly obese female patients with hypothyroidism and on thyroid replacement therapy who underwent LRYGB between January 2003 and August 2006. Mean preoperative body mass index (BMI) was 47.6 kg/m2 (range 38-58.5 kg/m2). Average patient age was 44.5 years (range 21-66 years). There was one early complication (pneumonia). Late complications included one death, three anastomotic strictures, and one small bowel obstruction. The patients were followed for a mean of 13.5 months (range 3-24 months). Their mean excess body weight loss was 13 kg (22%), 24.4 kg (39.4%), 33.2 kg (63.3%), 38.4 kg (65%), 41.7 kg (70%), and 43 kg (73%) at 1, 3, 6, 9, 12, and 24 months, respectively. Change in a mean BMI was the same regardless of the patient preoperative and postoperative thyroxine dose. Hypothyroidism resolved in 5(25%) patients, improved in 2(10%) patients, unchanged in 8(40%) patients, and worsened in 5 (25%) patients. Most of the five whose hypothyroidism worsened had thyroid autoimmune disease. Hypothyroidism appears to improve in the vast majority of morbidly obese patients who undergo LRYGB, except for those whose thyroid disease is autoimmune in nature.

Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment?

PubMed

Kovar, Florian Maria; Fang, I-Fei; Perkmann, Thomas; Haslacher, Helmuth; Slavka, Georg; Födinger, Manuela; Endler, Georg; Wagner, Oswald F

2015-12-01

Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality. Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7-1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry. A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7%) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females. Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

Analysis of Annual Changes in the Concentrations of Selected Macro- and Microelements, Thyroxine, and Testosterone in the Serum of Red Deer (Cervus elaphus) Stags.

PubMed

Kuba, J; Błaszczyk, B; Stankiewicz, T; Skuratko, A; Udała, J

2015-12-01

The aim of the study was to analyze seasonal changes in the concentrations of calcium, phosphorus, magnesium, and selenium as well as thyroxine and testosterone in adult red deer stags. The highest testosterone concentrations (mean 6.29±4.36 ng/ml) were observed from the end of August to November, confirming an increase in testicular secretory activity during the mating season. The changes in thyroxine concentration show circannual rhythms, most likely related to changes in the air temperature. The highest mean level of thyroxine was observed in spring (55.69±10.99 ng/ml). The concentration of selenium also reached the highest level during this season (0.107±0.027 μg/ml). In the case of the studied macroelements, the concentrations were stable from spring to summer but then decreased to the lowest mean values in autumn in both years of the experiment (Ca, 61.17±10.60; P, 47.08±9.59; Mg, 15.96±2.39 μg/ml). The dynamics of thyroxine secretion does not seem to affect directly the metabolism of calcium, phosphorus, and magnesium. In turn, sexual activity, manifested in the increase in secretion of testosterone, may affect changes in the concentration of calcium. Additionally, we cannot exclude a connection between changes in the concentrations of testosterone and selenium.

Hippocampal Neurometabolite Changes in Hypothyroidism: An In Vivo (1) H Magnetic Resonance Spectroscopy Study Before and After Thyroxine Treatment.

PubMed

Singh, S; Rana, P; Kumar, P; Shankar, L R; Khushu, S

2016-09-01

The hippocampus is a thyroid hormone receptor-rich region of the brain. A change in thyroid hormone levels may be responsible for an alteration in hippocampal-associated function, such as learning, memory and attention. Neuroimaging studies have shown functional and structural changes in the hippocampus as a result of hypothyroidism. However, the underlying process responsible for this dysfunction remains unclear. Therefore, the present study aimed to investigate the metabolic changes in the brain of adult hypothyroid patients during pre- and post-thyroxine treatment using in vivo proton magnetic resonance spectroscopy ((1) H MRS). (1) H MRS was performed in both healthy control subjects (n = 15) and hypothyroid patients (n = 15) (before and after thyroxine treatment). The relative ratios of the neurometabolites were calculated using the linear combination model (LCModel). Our results revealed a significant decrease of glutamate (Glu) (P = 0.045) and myo-inositol (mI) (P = 0.002) levels in the hippocampus of hypothyroid patients compared to controls. No significant changes in metabolite ratios were observed in the hypothyroid patients after thyroxine treatment. The findings of the present study reveal decreased Glu/tCr and mI/tCr ratios in the hippocampus of hypothyroid patients and these metabolite alterations persisted even after the patients became clinically euthyroid subsequent to thyroxine treatment. © 2016 British Society for Neuroendocrinology.

77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

.... FDA-2012-N-1148] FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products... comments. SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day public hearing to obtain...

[Clinical treatment with anti-thyroid drugs or iodine-131 therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis].

PubMed

Cruz Júnior, Antônio Fiel; Takahashi, Míriam Hideco; Albino, Cláudio Cordeiro

2006-12-01

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R dollars 1,345.81, while the RAI group spent a mean amount of R dollars 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

Effects of hepatic enzyme inducers on thyroxine (T4) catabolism in primary rat hepatocytes

EPA Science Inventory

Nuclear receptor agonists such as phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 3-methylcholantrene (3-MC) decrease circulating thyroxine (T4) concentrations in rats. It is suspected that this decrease occurs through the induction of hepatic metabolizing en...

HEPATIC ENZYME INDUCERS INCREASE THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES

EPA Science Inventory

Nuclear receptor agonists such as 3-methylcholantrene (3-MC), phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. It appears that this decrease occurs through the induction...

Predictive Modeling of a Mixture of Thyroid Hormone Disrupting Chemicals that Affect Production and Clearance of Thyroxine

EPA Science Inventory

Thyroid hormone (TH) disrupting compounds interfere with both thyroidal and extrathyroidal mechanisms to decrease circulating thyroxine (T4). This research tested the hypothesis that serum T4 concentrations of rodents exposed to a mixture of both TH synthesis inhibitors (pesticid...

The economic impact of battery longevity in implantable cardioverter-defibrillators for cardiac resynchronization therapy: the hospital and healthcare system perspectives.

PubMed

Landolina, Maurizio; Morani, Giovanni; Curnis, Antonio; Vado, Antonello; D'Onofrio, Antonio; Bianchi, Valter; Stabile, Giuseppe; Crosato, Martino; Petracci, Barbara; Ceriotti, Carlo; Bontempi, Luca; Morosato, Martina; Ballari, Gian Paolo; Gasparini, Maurizio

2017-08-01

Patients receiving cardiac resynchronization therapy defibrillators (CRT-Ds) are likely to undergo one or more device replacements, mainly for battery depletion. We assessed the economic impact of battery depletion on the overall cost of CRT-D treatment from the perspectives of the healthcare system and the hospital. We also compared devices of different generations and from different manufacturers in terms of therapy cost. We analysed data on 1792 CRT-Ds implanted in 1399 patients in 9 Italian centres. We calculated the replacement probability and the total therapy cost over 6 years, stratified by device generation and manufacturer. Public tariffs from diagnosis-related groups were used together with device prices and hospitalization costs. Generators were from 3 manufacturers: Boston Scientific (667, 37%), Medtronic (973, 54%), and St Jude Medical (152, 9%). The replacement probability at 6 years was 83 and 68% for earlier- and recent-generation devices, respectively. The need for replacement increased total therapy costs by more than 50% over the initial implantation cost for hospitals and by more than 30% for healthcare system. The improved longevity of recent-generation CRT-Ds reduced the therapy cost by ∼6% in both perspectives. Among recent-generation CRT-Ds, the replacement probability of devices from different manufacturers ranged from 12 to 70%. Consequently, the maximum difference in therapy cost between manufacturers was 40% for hospitals and 19% for the healthcare system. Differences in CRT-D longevity strongly affect the overall therapy cost. While the use of recent-generation devices has reduced the cost, significant differences exist among currently available systems. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

The pharmacokinetics and extracorporeal removal of N-acetylcysteine during renal replacement therapies.

PubMed

Hernandez, Stephanie H; Howland, Maryann; Schiano, Thomas D; Hoffman, Robert S

2015-01-01

Acetaminophen-induced fulminant hepatic failure is associated with acute kidney injury, metabolic acidosis, and fluid and electrolyte imbalances, requiring treatment with renal replacement therapies. Although antidote, acetylcysteine, is potentially extracted by renal replacement therapies, pharmacokinetic data are lacking to guide potential dosing alterations. We aimed to determine the extracorporeal removal of acetylcysteine by various renal replacement therapies. Simultaneous urine, plasma and effluent specimens were serially collected to measure acetylcysteine concentrations in up to three stages: before, during and upon termination of renal replacement therapy. Alterations in pharmacokinetics were determined by applying standard pharmacokinetic equations. Over 2 years, 10 critically ill patients in fulminant hepatic failure requiring renal replacement therapy coincident with acetylcysteine were consecutively enrolled. All 10 patients required continuous venovenous hemofiltration (n = 10) and 2 of the 10 also required hemodialysis (n = 2). There was a significant alteration in the pharmacokinetics of acetylcysteine during hemodialysis; the area under the curve (AUC) decreased 41%, the mean extraction ratio was 51%, the mean hemodialytic clearance was 114.01 ml/kg/h, and a mean 166.75 mg/h was recovered in the effluent or 41% of the hourly dose. Alteration in the pharmacokinetics of acetylcysteine during continuous venovenous hemofiltration did not appear to be significant: the AUC decreased 13%, the mean clearance was 31.77 ml/kg/h and a mean 62.12 mg/h was recovered in the effluent or 14% of the hourly dose. There was no significant extraction of acetylcysteine from continuous venovenous hemofiltration. In contrast, there was significant extracorporeal removal of acetylcysteine during hemodialysis. A reasonable dose adjustment may be to double the IV infusion rate or possibly supplement with oral acetylcysteine during hemodialysis.

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

PubMed

Li, Bernadette; Cairns, John A; Fotheringham, James; Tomson, Charles R; Forsythe, John L; Watson, Christopher; Metcalfe, Wendy; Fogarty, Damian G; Draper, Heather; Oniscu, Gabriel C; Dudley, Christopher; Johnson, Rachel J; Roderick, Paul; Leydon, Geraldine; Bradley, J Andrew; Ravanan, Rommel

2015-10-01

In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Effect of central hypothyroidism on Doppler-derived myocardial performance index.

PubMed

Doin, Fabio Luiz Casanova; Borges, Mariana da Rosa; Campos, Orlando; de Camargo Carvalho, Antonio Carlos; de Paola, Angelo Amato Vincenzo; Paiva, Marcelo Goulart; Abucham, Julio; Moises, Valdir Ambrosio

2004-06-01

Myocardial performance index (MPI) has been used to assess global ventricular function in different types of cardiac disease. Thyroid hormones influence cardiac performance directly and indirectly by changes in peripheral circulation. The aim of this study was to evaluate the possible effect of central hypothyroidism (CH) on MPI. The study included 28 control subjects and 7 patients with CH without cardiac disease. MPI was defined as the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time divided by ejection time. Patients were submitted to hormonal therapy with thyroxin and the study was repeated after 35 to 42 days. MPI was significantly higher in patients with CH (0.54 +/- 0.08) than in control subjects (0.40 +/- 0.05) (P =.002). The increase in MPI was caused by the prolongation of ICT without a significant variation of isovolumetric relaxation time and ejection time. After hormonal therapy there was a significant reduction of MPI (0.54 +/- 0.08 vs 0.42 +/- 0.07; P =.028) and ICT. MPI was increased in patients with untreated CH. The increase was related to prolongation of ICT and reverted by hormonal therapy.

[Hot rods in the ICU : What is the antibiotic mileage of your renal replacement therapy?

PubMed

Kielstein, J T; Kruse, A K; Anderson, N; Vaitiekunas, H; Scherneck, S

2017-05-08

We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics. Unlike catecholamines, where we have the mean arterial pressure on our ICU dashboard, we do not have a gauge to measure antibiotic "consumption", i.e. elimination by renal replacement therapy. This manuscript describes the principles and basic knowledge to improve dosing of antibiotics in critically ill patients undergoing renal replacement therapy. As in modern cars, we briefly touch on hybrid therapies combining renal replacement therapy with extracorporeal lung support or adsorbent technologies that remove cytokines or bacteria. Further, the importance of considering body size and body composition is addressed, especially for choosing the right initial dose of antibiotics. Lastly we point out the dire need to increase the availability of timely and affordable therapeutic drug monitoring on the most commonly used antiinfectives, ideally using point-of-care devices at the bedside.

Report on the National Eye Institute Audacious Goals Initiative: Replacement of Retinal Ganglion Cells from Endogenous Cell Sources.

PubMed

Vetter, Monica L; Hitchcock, Peter F

2017-03-01

This report emerges from a workshop convened by the National Eye Institute (NEI) as part of the "Audacious Goals Initiative" (AGI). The workshop addressed the replacement of retinal ganglion cells (RGCs) from exogenous and endogenous sources, and sought to identify the gaps in our knowledge and barriers to progress in devising cellular replacement therapies for diseases where RGCs die. Here, we briefly review relevant literature regarding common diseases associated with RGC death, the genesis of RGCs in vivo, strategies for generating transplantable RGCs in vitro, and potential endogenous cellular sources to regenerate these cells. These topics provided the clinical and scientific context for the discussion among the workshop participants and are relevant to efforts that may lead to therapeutic approaches for replacing RGCs. This report also summarizes the content of the workshop discussion, which focused on: (1) cell sources for RGC replacement and regeneration, (2) optimizing integration, survival, and synaptogenesis of new RGCs, and (3) approaches for assessing the outcomes of RGC replacement therapies. We conclude this report with a summary of recommendations, based on the workshop discussions, which may guide vision scientists seeking to develop therapies for replacing RGCs in humans.

Apparent electric charge of protein molecules. Human thyroxine - binding proteins.

PubMed

Hocman, G; Sadlon, J

1977-01-01

1. By comparison of electrophoretic mobilities of two different charged particles under the same conditions the net elementary electrostatic charge of one particle could be calculated when the charge of the other is known. 2. The electrophoretic mobility of human thyroxine - binding globulin does not depend upon the concentration of Tris - HCl buffer in the range 0.05 to 0.20 molar. The value of this mobility is 0.078 and 0.083 cm2 vol(-1) hour(-1) at pH 7.0 and 8.6, respectively. 3. The net elementary electrostatic charge of the human thyroxine - binding globulin appears to be approximately 22 negative elementary electrostatic units in mild alkaline solutions.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

PubMed

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

The seizure, not electricity, is essential in convulsive therapy: the flurothyl experience.

PubMed

Fink, Max

2014-06-01

For more than 50 years, research in convulsive therapy has been focused on the impact of electricity and seizures on memory and not on brain chemistry or neurophysiology. Brief pulse and ultra-brief pulse currents replaced sinusoidal currents. Electrode placements were varied, energy dosing was altered, and electricity was replaced by magnetic currents. The published experiences and archival records of seizures induced by camphor, pentylenetetrazol, and flurothyl are reviewed and compared with the changes induced by electricity. The clinical efficacy of chemically induced seizures is equal to that of electrical inductions. Seizure durations are longer, and impairment of cognition and memory is less. Electroconvulsive therapy replaced chemical treatments for ease of use, not for greater efficacy or safety. The brain seizure, not the method of induction, is the essential element in the efficacy of convulsive therapy. Seizure induction with chemicals avoids the direct effects of electricity on brain functions with lesser effects on cognition. Reexamination of chemical inductions of seizures as replacements for electricity is encouraged.

Beneficial prenatal levodopa therapy in autosomal recessive guanosine triphosphate cyclohydrolase 1 deficiency.

PubMed

Brüggemann, Norbert; Spiegler, Juliane; Hellenbroich, Yorck; Opladen, Thomas; Schneider, Susanne A; Stephani, Ulrich; Boor, Rainer; Gillessen-Kaesbach, Gabriele; Sperner, Jürgen; Klein, Christine

2012-08-01

To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia. Case reports, literature review, and video presentation. University of Lübeck, Lübeck, Germany. Two boys from a consanguineous family. Physical and mental development as a function of replacement initiation. The older sibling presented with typical features of AR GTPCH deficiency due to a homozygous mutation in the GCH1 gene with proven pathogenicity. Levodopa treatment was initiated at age 10 months and resulted in a distinct motor improvement. However, mental development was delayed. In the younger sibling, prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH deficiency was made. At age 17 months, both motor and mental development were normal for his age. This report highlights the importance of an early diagnosis, including prenatal diagnosis, of complex dopa-responsive extrapyramidal syndromes. Prenatally initiated dopaminergic replacement therapy is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of significant impairment of mental abilities.

New Product Marketing Blurs the Line Between Nicotine Replacement Therapy and Smokeless Tobacco Products.

PubMed

Kostygina, Ganna; England, Lucinda; Ling, Pamela

2016-07-01

Tobacco companies have begun to acquire pharmaceutical subsidiaries and recently started to market nicotine replacement therapies, such as Zonnic nicotine gum, in convenience stores. Conversely, tobacco companies are producing tobacco products such as tobacco chewing gum and lozenges that resemble pharmaceutical nicotine replacement products, including a nicotine pouch product that resembles snus pouches. This convergence of nicotine and tobacco product marketing has implications for regulation and tobacco cessation.

Enzyme replacement and substrate reduction therapy for Gaucher disease.

PubMed

Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

2015-03-27

Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy.Treatment-naïve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose.A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment.There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat.One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety - with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition.

Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy: A Randomized Controlled Trial.

PubMed

Fealy, Nigel; Aitken, Leanne; du Toit, Eugene; Lo, Serigne; Baldwin, Ian

2017-10-01

To determine whether blood flow rate influences circuit life in continuous renal replacement therapy. Prospective randomized controlled trial. Single center tertiary level ICU. Critically ill adults requiring continuous renal replacement therapy. Patients were randomized to receive one of two blood flow rates: 150 or 250 mL/min. The primary outcome was circuit life measured in hours. Circuit and patient data were collected until each circuit clotted or was ceased electively for nonclotting reasons. Data for clotted circuits are presented as median (interquartile range) and compared using the Mann-Whitney U test. Survival probability for clotted circuits was compared using log-rank test. Circuit clotting data were analyzed for repeated events using hazards ratio. One hundred patients were randomized with 96 completing the study (150 mL/min, n = 49; 250 mL/min, n = 47) using 462 circuits (245 run at 150 mL/min and 217 run at 250 mL/min). Median circuit life for first circuit (clotted) was similar for both groups (150 mL/min: 9.1 hr [5.5-26 hr] vs 10 hr [4.2-17 hr]; p = 0.37). Continuous renal replacement therapy using blood flow rate set at 250 mL/min was not more likely to cause clotting compared with 150 mL/min (hazards ratio, 1.00 [0.60-1.69]; p = 0.68). Gender, body mass index, weight, vascular access type, length, site, and mode of continuous renal replacement therapy or international normalized ratio had no effect on clotting risk. Continuous renal replacement therapy without anticoagulation was more likely to cause clotting compared with use of heparin strategies (hazards ratio, 1.62; p = 0.003). Longer activated partial thromboplastin time (hazards ratio, 0.98; p = 0.002) and decreased platelet count (hazards ratio, 1.19; p = 0.03) were associated with a reduced likelihood of circuit clotting. There was no difference in circuit life whether using blood flow rates of 250 or 150 mL/min during continuous renal replacement therapy.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

PubMed

Dogansen, Sema Ciftci; Yalin, Gulsah Yenidunya; Canbaz, Bulent; Tanrikulu, Seher; Yarman, Sema

2018-01-01

The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES INCREASES FOLLOWING EXPOSURE TO PROTOTYPICAL HEPATIC ENZYME INDUCERS

EPA Science Inventory

Nuclear receptor agonists such as phenobarbital (PB), 3-methylcholantrene (3MC), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. This decrease is thought to occur through the induction of ...

Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance

EPA Science Inventory

Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

THYROXINE (T4) CATABOLISM IN HUMAN AND RAT HEPATOCYTES INCREASES FOLLOWING EXPOSURE TO HEPATIC ENZYME INDUCERS

EPA Science Inventory

Nuclear receptor agonists phenobarbital (PB), 3-methylcholanthrene (3MC), pregnenolone-16a-carbonitrile (PCN), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 2,2' ,4,4'-tetrabromodiphenyl ether (BDE 47) decrease serum thyroxine (T4) in rats. This decrease is thought to occur th...

Triclosan Disrupts Thyroxine: Contribution of Hepatic Transport to the Mode of Action

EPA Science Inventory

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (TCS) decreases serum thyroxine (T4) in rats. In previous work, TCS upregulated Phase I and II hepatic metabolism after 4-day exposures in rats. A major data gap in our characterization of the mode of action (MOA) of TCS-induced ...

Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action

EPA Science Inventory

This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

PCB-153 AND BDE-47 INCREASE THYROXINE T4) CATABOLISM IN RAT AND HUMAN HEPATOCYTES

EPA Science Inventory

Previous studies demonstrate that in vivo exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decrease serum thyroxine (T4) levels in rats. This decrease is thought to occur through the induction of hepatic metabolizing enzymes ...

TEMPORAL AND SPATIAL VARIATION IN PLASMA THYROXINE (T4) CONCENTRATIONS IN JUVENILE ALLIGATORS COLLECTED FROM LAKE OKEECHOBEE AND THE NORTHERN EVERGLADES, FLORIDA, USA

EPA Science Inventory

We examined variation in plasma thyroxine (T4) in juvenile American alligators (Alligator mississippiensis) collected from three sites within the Kissimmee River drainage basin (FL, USA). Based on historical sediment data, Moonshine Bay served as the low contaminant exposure site...

[Assisted peritoneal dialysis: home-based renal replacement therapy for the elderly patient].

PubMed

Wiesholzer, Martin

2013-06-01

The number of elderly patients with end stage renal disease is constantly increasing. Conventional hämodiaylsis as the mainstay of renal replacement therapy is often poorly tolerated by frail eldery patients with multiple comorbidities. Although many of these patients would prefer a home based dialysis treatment, the number of elderly patients using peritoneal dialysis (PD) is still low. Impaired physical and cognitive function often generates insurmountable barriers for self care peritoneal dialysis. Assisted peritoneal dialysis can overcome many of these barriers and give elderly patients the ability of a renal replacement therapy in their own homes respecting their needs.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W; Hoermann, Rudolf

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

PubMed

Keleştimur, F; Aksu, A

1996-01-01

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Effect of subclinical hypothyroidism on the skeletal system and improvement with short-term thyroxine therapy.

PubMed

Gao, Cuixia; Wang, Yu; Li, Tingting; Huang, Jing; Tian, Limin

2017-10-27

The purpose of the study was to observe changes in the skeletal system of rats with subclinical hypothyroidism (SCH) and to determine whether L-thyroxine (L-T4) administration suppresses those changes. Sixty male Wistar rats were randomly divided into control, SCH, and SCH+T4 groups. SCH was induced in rats by administration of methimazole (MMI), and rats in the SCH+T4 group were treated with L-T4 after 45 days of MMI administration. The SCH group had higher thyroid-stimulating hormone (TSH) level than the control and SCH+T4 groups. There were no differences in serum thyroid hormone (FT4 and FT3) levels among the three groups. Bone mineral density; serum levels of BALP and TRACP-5b, two bone metabolic markers; and the biomechanical properties of the femurs were lower in the SCH group than in the control group. After L-T4 treatment, serum BALP and TRACP-5b levels and the femur biomechanical properties were higher in the SCH+T4 than the SCH group. Histopathological examination revealed damage to the structure of the femur trabecular bone network in rats with SCH, and L-T4 treatment improved this condition to some extent. These findings demonstrate that L-T4 treatment ameliorates the destructive effects of SCH on the skeletal system in rats.

Interleukin-12 plasmid DNA delivery using l-thyroxine-conjugated polyethylenimine nanocarriers

NASA Astrophysics Data System (ADS)

Dehshahri, Ali; Sadeghpour, Hossein; Kazemi Oskuee, Reza; Fadaei, Mahin; Sabahi, Zahra; Alhashemi, Samira Hossaini; Mohazabieh, Erfaneh

2014-05-01

In this study, l-thyroxine was covalently grafted on 25 kDa branched polyethylenimine (PEI), and the ability of the nano-sized polyplexes for transferring plasmid encoding interleukin-12 (IL-12) gene was evaluated. As there are several problems in systemic administration of recombinant IL-12 protein, local expression of the plasmid encoding IL-12 gene inside the tumor tissue has been considered as an effective alternative approach. The l-thyroxine-conjugated PEI polyplexes were prepared using pUMVC3-hIL12 plasmid, and their transfection activity was determined in HepG2 human liver carcinoma and Neuro2A neuroblastoma cell lines. The polyplexes characterized in terms of DNA condensation ability, particle size, zeta potential, and buffering capacity as well as cytotoxicity and resistance to enzyme digestion. The results revealed that l-thyroxine conjugation of PEI increased gene transfer ability by up to two fold relative to unmodified 25 kDa PEI, the gold standard for non-viral gene delivery, with the highest increase occurring at degrees of conjugation around 10 %. pDNA condensation tests and dynamic light scattering measurements exhibited the ability of PEI conjugates to optimally condense the plasmid DNA into polyplexes in the size range around 200 nm. The modified polymers showed remarkable buffering capacity and protection against enzymatic degradation comparable to that of unmodified PEI. These results suggest that l-thyroxine conjugation of PEI is a simple modification strategy for future investigations aimed at developing a targeting gene vehicle.

Baseline Levels and Trimestral Variation of Triiodothyronine and Thyroxine and Their Association with Mortality in Maintenance Hemodialysis Patients

PubMed Central

Meuwese, Christiaan L.; Dekker, Friedo W.; Lindholm, Bengt; Qureshi, Abdul R.; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J.

2012-01-01

Summary Background and objectives Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. Design, setting, participants, & measurements In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models. Results During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Conclusions Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect. PMID:22246282

Baseline levels and trimestral variation of triiodothyronine and thyroxine and their association with mortality in maintenance hemodialysis patients.

PubMed

Meuwese, Christiaan L; Dekker, Friedo W; Lindholm, Bengt; Qureshi, Abdul R; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J

2012-01-01

Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan-Meier curves and Cox proportional hazard models. During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect.

Unusual Ratio between Free Thyroxine and Free Triiodothyronine in a Long-Lived Mole-Rat Species with Bimodal Ageing

PubMed Central

Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

2014-01-01

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine. PMID:25409169

Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

PubMed

Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

2014-01-01

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

Role of L-thyroxin in counteracting rotenone induced neurotoxicity in rats.

PubMed

Salama, Mohamed; Helmy, Basem; El-Gamal, Mohamed; Reda, Amr; Ellaithy, Amr; Tantawy, Dina; Mohamed, Mie; El-Gamal, Aya; Sheashaa, Hussein; Sobh, Mohamed

2013-03-01

A key feature of Parkinson's disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Many triggering pathways have been incriminated in the pathogenesis of this disease including inflammation, oxidative stress, excitotoxicity and apoptosis. Thyroid hormone is an essential agent for the growth and maturation of neurons; moreover, it has variable mechanisms for neuroprotection. So, we tested the efficacy of (L)-thyroxin as a neuroprotectant in rotenone model of Parkinson's disease in rats. Thirty Sprague Dawley rats aged 3 months were divided into 3 equal groups. The first received daily intraperitoneal injections of 0.5% carboxymethyl cellulose (CMC) 3 mL/Kg. The second group received rotenone suspended in 0.5% CMC intraperitoneally at a dose of 3 mg/kg, daily. The third group received the same rotenone regimen subcutaneous l-thyroxine at a dose of 7.5 μg daily. All animals were evaluated regarding locomotor disturbance through blinded investigator who monitored akinesia, catalepsy, tremors and performance in open field test. After 35 days the animals were sacrificed and their brains were immunostained against anti-tyrosine hydroxylase and iba-1. Photomicrographs for coronal sections of the substantia nigra and striatum were taken and analyzed using image J software to evaluate cell count in SNpc and striatal fibers density and number of microglia in the nigrostriatal system. The results were then analyzed statistically. Results showed selective protective effects of thyroxin against rotenone induced neurotoxicity in striatum, however, failed to exert similar protection on SN. Moreover, microglial elevated number in nigrostriatal system that was induced by rotenone injections was diminished selectively in striatum only in the l-thyroxin treated group. One of the possible mechanisms deduced from this work was the selective regulation of microglia in striatal tissues. Thus, this study provides an insight into thyroxin neuroprotection warranting further investigation as therapeutic option for Parkinson's disease patients. Copyright © 2013 Elsevier B.V. All rights reserved.

The Effect of Thyroid Hormone, Prostaglandin E2, and Calcium Gluconate on Orthodontic Tooth Movement and Root Resorption in Rats.

PubMed

Seifi, Massoud; Hamedi, Roya; Khavandegar, Zohre

2015-03-01

A major objective of investigators is to clarify the role of metabolites in achievement of maximum tooth movement with minimal root damage during orthodontic tooth movement (OTM). The aim of this study was to determine the effect of administration of thyroid hormone, prostaglandin E2, and calcium on orthodontic tooth movement and root resorption in rats. Sixty four male Wistar rats were randomly divided into 8 groups of eight rats each: 1- 20µg/kg thyroxine was injected in traperitoneally after installation of the orthodontic appliance.  2- 0.1 ml of 1 mg/ml prostaglandin E2 was injected submucosally.  3- 10% (200 mg/kg) calcium gluconate was injected.  4- Prostaglandin E2 was injected submucosally and 10% calcium was injected intraperitoneally.  5- Thyroxine was injected intraperitoneally and prostaglandin E2 was injected submucosally.  6- 20µg/kg thyroxine with calcium was injected. 7- Prostaglandin E2 was injected submucosally with calcium and thyroxine.  8- Distilled water was used in control group. The orthodontic appliances comprised of a NiTi closed coil were posteriorly connected to the right first molar and anteriorly to the upper right incisor. OTM was measured with a feeler gauge. The mid-mesial root of the first molar and the adjacent tissues were histologically evaluated. The Data were analyzed by one-way ANOVA and Student-Newman-Keuls test. The highest mean OTM was observed in the thyroxine and prostaglandin E2 group (Mean±SD = 0.7375±0.1359 mm) that was significantly different (p< 0.05). A significant difference (p< 0.05) in root resorption was observed between the prostaglandin E2 (0.0192±0.0198 mm(2)) and the other groups. It seems that the combination of thyroxine and prostaglandin E2, with a synergistic effect, would decrease the root resorption and increase the rate of orthodontic tooth movement in rats.

[Vomiting as main symptom: unusual presentation of a hyperthyroidism in a 12-year-old boy].

PubMed

Müller-Michaels, J; Bürk, G; Andler, W

1997-01-01

A twelve year old boy presented with a sudden onset of recurrent nausea and vomiting. During the past six weeks he had a weight loss of 13 kg. While he was in the hospital, persistent tachycardia and a slightly elevated blood pressure were noted. The gastroenterologic, cardiologic and neuropediatric examinations were normal. To exclude the differential diagnosis of hyperthyroidism, thyroid hormones were checked. They showed clearly elevated levels of tri-iodothyronine and thyroxine, while thyrotropin was suppressed. The boy did not have a goiter. Under thyrostatic therapy his clinical condition improved quickly. Among our 20 patients with hyperthyroidism he was the only one whose main symptom was severe vomiting.

Vitiligo and alopecia areata associated with subclinical/clinical hypothyroidism.

PubMed

Sehgal, Virendra N

2011-01-01

The parents of an 18-year-old woman had noticed white hair while combing their daughter's hair 12 years ago. They found tiny white spots on her scalp, but she was asymptomatic. The spots have since progressed. Examination of the affected skin on the scalp was marked by the presence of a chalky/ivory white macule, 8 to 10 cm in diameter, conforming to that of segmental (zosteriformis) vitiligo (Figure 1). The lesions were located on the temporoparietal region of the scalp. The hair over the macules was white (leukotrichia) and dry, coarse, and brittle. The patient's nails were thin and dull. Her thyroid profile revealed the following: triiodothyronine, 1.12 nmol/L (0.95-2.5 nmol/L); thyroxine, 69.21 nmol/L (60.0-120.0 nmol/L); and thyroid-stimulating hormone, 6.26 microIU/mL (0.25-5.00 microIU/mL), indicative of primary hypothyroidism. Liver and renal function tests were within normal limits. A lipid profile revealed the following: total lipids, 503.8 mg% (400-700 mg %); triglycerides, 123.0 mg % (160 mg %); cholesterol, 212.0 mg % (150-250 mg %); high-density lipoprotein, 43.1 mg % (30-63 mg %); and low-density lipoprotein, 144.3 mg % (50 mg %). Electrocardiographic findings were normal. History of tiredness, constipation, depression, sensitivity to cold, weight gain, muscle weakness, cramps, and increased menstrual flow supported the diagnosis. The patient was administered 100 microg of thyroxine once a day along with methoxsalen, the dose of which was calculated at 0.6 mg/kg to 0.7 mg/kg body weight per day given on alternate days, followed 2 hours later by exposure to UV-A (1 J/cm2) irradiation (psoralen-UV-A [PUVA]), supplemented by 1 mg of beta-methasone, 150 mg of levamisole on 2 consecutive days per week, and an antioxidant. During the course of 7 weeks, the macules (13 exposures) had become erythematous, with an appearance of perifollicular/ marginal pigmentation. Repeat examination showed a thyroid profile of total triiodothyronine (T3), 127.3 microg/dL (86-186); total thyroxine (T4), 6.54 microg/dL (4.5-12.5 microg/dL); and thyroid-stimulating hormone (TSH), 0.32 microIU/mL (0.3-5.6 microIU/mL), supplemented by antithyroid microsomal peroxidase antibodies (thyroid microsomal antibody and thyroid peroxidase), 21.9 IU/mL (1-40 IU/mL), and antithyroglobulin antibodies, 78.1 U/mL (1-100 U/mL). During the patient's treatment period, 4 other patients with clinical symptoms and signs of long-standing hypothyroidism developed vitiligo, the duration of which was variable in each patient (Table I). All of the patients were taking thyroxin. Thyroid and lipid profiles were performed periodically to evaluate the progress (Table I). These patients were also treated with PUVA therapy and thyroxin. During the course of treatment, 2 of the patients noticed asymptomatic, progressive, localized, and well-circumscribed hair loss at the temporal region of the scalp that extended to involve the vertex, conforming to findings of alopecia areata (Figure 2A and Figure 2B).

Hypothyroidism in adults. Levothyroxine if warranted by clinical and laboratory findings, not for simple TSH elevation.

PubMed

2015-10-01

Hypothyroidism is a common disorder due to inadequate thyroid hormone secretion. When a patient has signs and symptoms suggestive of hypothyroidism, how is it determined whether thyroid hormone replacement therapy will have a favourable harm-benefit balance? How should treatment be managed? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. The symptoms of hypothyroidism are due to slow metabolism (constipation, fatigue, sensitivity to cold, weight gain, etc.) and to polysaccharide accumulation in certain tissues, leading to hoarseness, eyelid swelling, etc. A blood TSH concentration of less than 4 or 5 mlU/L rules out peripheral hypothyroidism. TSH levels increase with age. Between 30% and 60% of high TSH levels are not confirmed on a second blood test. In overt hypothyroidism, the TSH level is high and the free T4 (thyroxine) level is low. Most of these patients are symptomatic. So-called subclinical hypothyroidism, which is rarely symptomatic, is characterised by high blood TSH levels and normal free T4 levels. The natural history of hypothyroidism depends on its cause. In chronic autoimmune thyroiditis, the most common form seen in rich countries, hypothyroidism generally worsens over time. However, other situations can lead to transient hypothyroidism that may last several weeks or months. Subclinical hypothyroidism, as the name implies, is usually asymptomatic. The risk of progression to overt hypothyroidism is about 3% to 4% per year overall but increases with the initial TSH level. Treatment guidelines are mainly based on physiological and pharmacological considerations and generally recommend levothyroxine therapy. The adverse effects of levothyroxine are signs of thyrotoxicosis in case of overdose (tachycardia, tremor, sweating, etc.). Even a slight overdose carries a risk of osteoporotic fractures and atrial fibrillation, especially in the elderly. In young adults, levothyroxine is usually started at a dose of about 1.5 microg/kg per day, taken on an empty stomach. Elderly patients and those with coronary artery disease should start at a lower dose: 12.5 to 50 microg per day. Treatment monitoring is based mainly on blood TSH assay. Dose adjustment should only be considered after 6 to 12 weeks, given the long half-life of levothyroxine. Certain drugs, such as iron and calcium, reduce the gastrointestinal absorption of levothyroxine. Enzyme inducers reduce its efficacy. In 2015, there is no robust evidence that levothyroxine therapy has any tangible benefit in patients with subclinical hypothyroidism. Some practice guidelines recommend treatment when the TSH level is above 10 mIU/L, or sometimes trial treatment for a few months for patients with symptoms suggestive of hypothyroidism. In practice, replacement therapy is needed for patients with overt hypothyroidism and a blood TSH concentration above 10 mIU/L. The main challenge is to recognise transient hypothyroidism, which does not require life-long treatment. When the TSH is only slightly elevated, there is a risk of attributing non-specific symptoms to an abnormal laboratory result and prescribing unnecessary treatment. Watchful waiting is an alternative to routine levothyroxine prescription in case of TSH elevation.

A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

ERIC Educational Resources Information Center

Patten, Christi A.

2000-01-01

Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

Getting to the heart of hypopituitarism.

PubMed

Martin-Grace, Julie; Ahmed, Mohamed; Mulvihill, Niall; Feeney, Eoin R; Crowley, Rachel K

2017-04-01

A 53-year-old woman was diagnosed with hypopituitarism following an acute presentation with cardiac tamponade and hyponatraemia, having recently been investigated for a pericardial effusion. Secondary hypothyroidism is a rare cause of pericardial effusion and tamponade, but an important differential to consider. Management requires appropriate hormone replacement and, critically, a low threshold for commencing stress dose steroids. Clinical signs classically associated with cardiac tamponade are frequently absent in cases of tamponade due to primary and secondary hypothyroidism, and the relatively volume deplete state of secondary hypoadrenalism in hypopituitarism may further mask an evolving tamponade, as the rise in right atrial pressure is less marked even in the presence of large effusion. Our case demonstrates the importance of a high index of suspicion for cardiac tamponade in this patient cohort, even in the absence of clinical signs, and for measuring both thyroid-stimulating hormone and thyroxine levels when evaluating a pericardial effusion. © Royal College of Physicians 2017. All rights reserved.

Hypothyroidism and acute kidney injury: an unusual association.

PubMed

Neves, Precil Diego Miranda de Menezes; Bridi, Ramaiane Aparecida; Balbi, André Luis; Ponce, Daniela

2013-08-09

Association between severe hypothyroidism and acute kidney injury (AKI) is rare. A 40-year-old woman presented with 15 days history of generalised muscle pain, weakness, weight gain and oedema. hypertension and hypothyroidism. dry skin, peripheral/periorbital oedema, slow thought and speaking, thyroid increased. Laboratory examinations: high levels of creatine kinase , creatinine, uric acid and lactate dehydrogenase. Free T4 was very low (<0.3 ng/dL) and thyroid-stimulating hormone was high (21.7 µIU/mL). Urinalysis showed haem pigment without haematuria. We performed the diagnosis of AKI secondary to hypothyroidism-induced rhabdomyolysis. Intravenous fluids were started, urinary alkalisation and increased l-thyroxine dose replacement. On the day after admission, forced diuresis with furosemide was introduced leading to a progressive improvement of symptoms. Although hypothyroidism and AKI is unusual, it should be suspected in patients presenting decrease of renal function and high creatine kinase in the absence of other causes of rhabdomyolysis.

Thyrotoxicosis in patients with hypothyroidism is not just overtreatment.

PubMed

Kempegowda, Punith; Nayak, Ananth U

2017-07-14

A 62-year-old Caucasian woman presented with hypothyroid symptoms and biochemical thyrotoxic picture. Previously, she underwent right-sided subtotal thyroidectomy and left partial thyroid lobectomy for thyroid lumps, and treated with thyroxine replacement for hypothyroidism. Although there were no significant findings on clinical examination, investigations confirmed thyrotoxicosis with positive autoimmunity against thyroid glandâ€"all in line with a diagnosis of Graves’ hyperthyroidism. We would like to highlight atypical presentations of thyroid dysfunction and conversion of underactive to overactive thyroid status with this case. Early recognition, diagnosis and intervention are essential to prevent and/or reduce associated morbidity and mortality. When encountered with such clinical conundrums, we recommend seeking opinion from an experienced endocrinologist while interpreting such situation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of alterations in metabolic rate on the duration of tolerance in neonatally injected animals.

PubMed

St Rose, J E; Murray, G W; Howe, S A

1976-01-01

Exposure to low environmental temperature caused a decrease in the half-life of human albumin (HA) in rabbits injected with 20 mg HA at birth, and a twofold increase in the proportion of animals which lost their tolerance by 150 days of age. Administration of thyroxin produced an even greater effect with respect to tolerance loss. Simlar mechanisms may be involved in the effects of cold exposure and thyroxin administration on tolerance duration. One possible mecahnism is that the duration of tolerance is dependent upon the metabolic half-life of the tolerance-inducing antigen. An alternative mechanism could be a cold- or thyroxin-induced enhancement of the recruitment of immunologically competent cells from an undifferentiated population of stem cells.

Safe and Successful Treatment With Agalsidase Beta During Pregnancy in Fabry Disease.

PubMed

Senocak Tasci, Elif; Bicik, Zerrin

2015-09-01

Fabry disease, an X-linked lysosomal storage disorder, is caused by α-galactosidase A deficiency and leads to accumulation of glycospinhgolipids in most tissues, with life-theratening consequences in the kidney, heart, and cerebrovascular system. Enzyme replacement therapy is available as 2 different preparations: agalsidase alfa and agalsidase beta. Enzyme replacement therapy is started as soon as the diagnosis is confirmed, but there is no data available in the literature about its safety during preganacy. Herein, we described 2 patients with Fabry disease who received agalsidase beta during their pregnancy. This report is important as the data about enzyme replacement therapy during pregnancy is restricted with case reports.

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

PubMed

De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

2016-01-01

Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Cue-Provoked Craving and Nicotine Replacement Therapy in Smoking Cessation

ERIC Educational Resources Information Center

Waters, Andrew J.; Shiffman, Saul; Sayette, Michael A.; Paty, Jean A.; Gwaltney, Chad J.; Balabanis, Mark H.

2004-01-01

Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were…

Intensity of continuous renal-replacement therapy in critically ill patients.

PubMed

Bellomo, Rinaldo; Cass, Alan; Cole, Louise; Finfer, Simon; Gallagher, Martin; Lo, Serigne; McArthur, Colin; McGuinness, Shay; Myburgh, John; Norton, Robyn; Scheinkestel, Carlos; Su, Steve

2009-10-22

The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.) 2009 Massachusetts Medical Society

High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

PubMed

Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-08-01

Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

High Phenobarbital Clearance During Continuous Renal Replacement Therapy

PubMed Central

Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-01-01

Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

[Ethical and legal issues concerning renal replacement therapy withdrawal or withholding].

PubMed

Radziszewski, Andrzej; Stompór, Tomasz; Gajda, Mariusz; Sułowicz, Władysław

2006-01-01

Rapid and dynamic increase of the number of patients that need different forms of renal replacement therapy can be noticed in the developed countries. This increase is associated with increased number of patients with 'diseases of modern civilization', such as diabetes and hypertension, which lead to kidney complications (e.g. diabetic and hypertensive nephropathy). Improved long-term care (especially diabetic and cardiologic) allows these patients to survive longer and to reach the stage of end-stage renal disease. This leads to increasing age and morbidity of patients treated with dialysis. In many cases, due to extremely advanced level of co-morbidity patients on dialysis are exposed to extreme level of suffering and unacceptably low quality of life. Persistent continuing of renal replacement therapy under such circumstances (with no hope for recovery or improvement) raises also some economical issues, especially in the context of permanent crisis and shortage of resources in health systems of most countries in the world. In this review the current practice concerning withdrawal or withholding of renal replacement therapy as well as some legal and ethical issues of this practice are discussed.

The effect of L-thyroxine replacement therapy on ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hypothyroidism.

PubMed

Erem, Cihangir; Suleyman, Akile Karacin; Civan, Nadim; Mentese, Ahmet; Nuhoglu, İrfan; Uzun, Aysegul; Coskun, Hulya; Deger, Orhan

2016-11-01

The main objective of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with subclinical (SHypo) and overt hypothyroidism (OHypo), and to assess the effects of levothyroxine (LT 4 ) therapy on the oxidative stress (OS) parameters. We also investigated the relationships among serum thyroid hormones, lipid parameters, and IMA and MDA in these patients. Thirty untreated patients with OHypo, 25 untreated patients with Shypo, and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters including IMA and MDA were evaluated in all patients just before and one month after the maintenance of euthyroidism. Compared with the control subjects, the levels of MDA and triglycerides (TG) significantly increased in patients with SHypo (p < 0.001 and p < 0.05, respectively), whereas high density lipoprotein cholesterol (HDL-C) levels significantly decreased (p = 0.01). Patients with OHypo showed significantly high MDA, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and TG levels (p = 0.001, p < 0.01, p = 0.01, and p < 0.01, respectively), and significantly low HDL-C levels compared with the controls (p < 0.05). MDA levels and lipid profile were not significantly different in the patients with OHypo when compared with the patients with SHypo. Serum IMA levels did not significantly change in patients with OHypo and SHypo compared with the controls. In the pre-treatment period, MDA levels were inversely correlated with HDL-C levels in patients with OHypo (r: -0.471, p = 0.009). Plasma MDA and LDL-C levels significantly decreased and HDL-C levels significantly increased in the groups of OHypo and SHypo after LT 4 treatment. Serum IMA levels did not significantly change with the therapy in all patient groups. Increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis seen in these patients. Increased OS in patients with SHypo and OHypo could be improved by LT 4 treatment. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

PubMed

Biondi, Bernadette; Wartofsky, Leonard

2012-07-01

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

PubMed

De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

2000-05-01

To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P-NMR study.

PubMed

Seymour, A M; Eldar, H; Radda, G K

1990-11-12

We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 micrograms/100 g body weight) over seven days. 31P-NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 mumols.(g dry wt.)-1 in control hearts to 11.7 mumols.(g dry wt.)-1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 mumols.(g dry wt.)-1 to 21.8 mumols.(g dry wt.)-1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi----ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine-treated hearts in comparison to control hearts (to 3.6 mumols.(g dry wt.)-1.s-1, from 1.6 mumols.(g dry wt.)-1.s-1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K(+)-ATPase pumps that occur in response to thyroxine treatment.

Thermal acclimation and thyroxine treatment modify the electric organ discharge frequency in an electric fish, Apteronotus leptorhynchus.

PubMed

Dunlap, K D; Ragazzi, M A

2015-11-01

In ectotherms, the rate of many neural processes is determined externally, by the influence of the thermal environment on body temperature, and internally, by hormones secreted from the thyroid gland. Through thermal acclimation, animals can buffer the influence of the thermal environment by adjusting their physiology to stabilize certain processes in the face of environmental temperature change. The electric organ discharge (EOD) used by weak electric fish for electrocommunication and electrolocation is highly temperature sensitive. In some temperate species that naturally experience large seasonal fluctuations in environmental temperature, the thermal sensitivity (Q10) of the EOD shifts after long-term temperature change. We examined thermal acclimation of EOD frequency in a tropical electric fish, Apteronotus leptorhynchus that naturally experiences much less temperature change. We transferred fish between thermal environments (25.3 and 27.8 °C) and measured EOD frequency and its thermal sensitivity (Q10) over 11 d. After 6d, fish exhibited thermal acclimation to both warming and cooling, adjusting the thermal dependence of EOD frequency to partially compensate for the small change (2.5 °C) in water temperature. In addition, we evaluated the thyroid influence on EOD frequency by treating fish with thyroxine or the anti-thyroid compound propylthiouricil (PTU) to stimulate or inhibit thyroid activity, respectively. Thyroxine treatment significantly increased EOD frequency, but PTU had no effect. Neither thyroxine nor PTU treatment influenced the thermal sensitivity (Q10) of EOD frequency during acute temperature change. Thus, the EOD of Apteronotus shows significant thermal acclimation and responds to elevated thyroxine. Copyright © 2015 Elsevier Inc. All rights reserved.

Testing for hypothyroidism in dogs.

PubMed

Ferguson, Duncan C

2007-07-01

Hypothyroidism is the most common endocrinopathy in the dog. Rather than being a comprehensive review of all possible thyroid function tests, the focus in this article is on the logical progression of test choice, highlighting total thyroxine, free thyroxine, triiodothyronine, thyrotropin (TSH), and antithyroid antibodies. This article includes extensive discussion of the current status of the canine TSH assay and the potential for improving this assay.

Effects of hyperthyroidism induced by L-thyroxin administration on lipid peroxidation in various rat tissues.

PubMed

Mogulkoc, R; Baltaci, A Kasim; Oztekin, Esma; Sivrikaya, A; Aydin, Leyla

2006-06-01

Thyroid dysfunctions are associated with many pathological signs in the body. One of these is lipid peroxidation that develops due to over- or under-secretion of thyroid hormones. The present study was conducted to determine lipid peroxidation that develops in different tissues including the brain, liver and heart of rats in experimental hyperthyroidism induced by L-thyroxin. The study was carried out on 30 male Sprague-Dawley rats. They were divided into three groups as control, sham hyperthyroidism and hyperthyroidism. Malondialdehyde (MDA) and glutathione (GSH) levels in rat tissues were determined at the end of a 3-weeks period of L-thyroxin administration. It was observed that MDA levels in the hyperthyroidism group were significantly higher in the cerebral cortex, liver and ventriculer tissue of heart (p < 0.001) than in the control and in sham hyperthyroidism groups. GSH levels were higher in the hyperthyroidism group than in control and sham hyperthyroidism groups in all tissues (p < 0.001). Results demonstrate that hyperthyroidism induced by L-thyroxin activates both oxidant and antioxidant systems in cerebral, hepatic and cardiac tissues. However, the increase in antioxidant activity cannot adequately prevent oxidative damage.

Theoretical and experimental study for the biomimetic recognition of levothyroxine hormone on magnetic molecularly imprinted polymer.

PubMed

Moura, Silio Lima; Fajardo, Laura Martinez; Cunha, Leonardo Dos Anjos; Sotomayor, Maria Del Pilar Taboada; Machado, Francisco Bolivar Correto; Ferrão, Luiz Fernando Araújo; Pividori, Maria Isabel

2018-06-01

This study addresses the rational design of a magnetic molecularly imprinted polymer (magnetic-MIP) for the selective recognition of the hormone levothyroxine. The theoretical study was carried out by the density functional theory (DFT) computations considering dispersion interaction energies, and using the D2 Grimme's correction. The B97-D/def2-SV(P)/PCM method is used not only for studying the structure of the template the and monomer-monomer interactions, but also to assess the stoichiometry, noncovalent binding energies, solvation effects and thermodynamics properties such as binding energy. Among the 13 monomers studied in silico, itaconic acid is the most suitable according to the thermodynamic values. In order to assess the efficiency of the computational study, three different magnetic-MIPs based on itaconic acid, acrylic acid and acrylamide were synthesized and experimentally compared. The theoretical results are in agreement with experimental binding studies based on laser confocal microscopy, magneto-actuated immunoassay and electrochemical sensing. Furthermore, and for the first time, the direct electrochemical sensing of L-thyroxine preconcentrated on magnetic-MIP was successfully performed on magneto-actuated electrodes within 30 min with a limit of detection of as low as 0.0356 ng mL -1 which cover the clinical range of total L-thyroxine. Finally, the main analytical features were compared with the gold standard method based on commercial competitive immunoassays. This work provides a thoughtful strategy for magnetic molecularly imprinted polymer design, synthesis and application, opening new perspectives in the integration of these materials in magneto-actuated approaches for replacing specific antibodies in biosensors and microfluidic devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Enteral nutrition in patients with acute renal failure.

PubMed

Fiaccadori, Enrico; Maggiore, Umberto; Giacosa, Roberto; Rotelli, Carlo; Picetti, Edoardo; Sagripanti, Sibilla; Melfa, Luigi; Meschi, Tiziana; Borghi, Loris; Cabassi, Aderville

2004-03-01

Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.

A randomized trial of nicotine-replacement therapy patches in pregnancy.

PubMed

Coleman, Tim; Cooper, Sue; Thornton, James G; Grainge, Matthew J; Watts, Kim; Britton, John; Lewis, Sarah

2012-03-01

Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy. We investigated the efficacy and safety of nicotine patches during pregnancy. We recruited participants from seven hospitals in England who were 16 to 50 years of age with pregnancies of 12 to 24 weeks' gestation and who smoked five or more cigarettes per day. Participants received behavioral cessation support and were randomly assigned to 8 weeks of treatment with active nicotine patches (15 mg per 16 hours) or matched placebo patches. The primary outcome was abstinence from the date of smoking cessation until delivery, as validated by measurement of exhaled carbon monoxide or salivary cotinine. Safety was assessed by monitoring for adverse pregnancy and birth outcomes. Of 1050 participants, 521 were randomly assigned to nicotine-replacement therapy and 529 to placebo. There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups (9.4% and 7.6%, respectively; unadjusted odds ratio with nicotine-replacement therapy, 1.26; 95% confidence interval, 0.82 to 1.96), although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group (21.3% vs. 11.7%). Compliance was low; only 7.2% of women assigned to nicotine-replacement therapy and 2.8% assigned to placebo used patches for more than 1 month. Rates of adverse pregnancy and birth outcomes were similar in the two groups. Adding a nicotine patch (15 mg per 16 hours) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes. However, low compliance rates substantially limited the assessment of safety. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Current Controlled Trials number, ISRCTN07249128.).

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Diagnosis and treatment of Graves' disease with particular emphasis on appropriate techniques in nuclear medicine. General state of knowledge.

PubMed

Prasek, Karolina; Płazińska, Maria Teresa; Królicki, Leszek

2015-01-01

Graves' disease is an autoimmune disease. It accounts for 50-80% of cases of hyperthyroidism. Antibodies against the TSH receptor (TRAb) are responsible for hyperthyroidism (TRAB). The key role in monitoring and diagnosis of Graves' disease plays the level of hormones of free thyroxine and triiodothyronine. Helpful is an ultrasound of the thyroid scintigraphy which due to its functional character is both a valuable addition to morphological studies as well as plays an important role in the diagnosis and therapy in patients with Graves' disease. There is no perfect treatment for Graves' disease. The reason for this is the lack of therapy directed against primary pathogenic mechanisms. Currently available treatments need to be thoroughly discussed during the first visit as the patient's understanding of the choice of a treatment constitutes a vital role in the success of therapy. Graves' disease treatment is based on three types of therapies that have been carried out for decades including: pharmacological treatment anti-thyroid drugs, I131 therapy and radical treatment - thyroidectomy. The purpose of the treatment is to control symptoms and patient to return to euthyreosis. Treatment of Graves' disease is of great importance because if left untreated, it can lead to long-term harmful effects on the heart, bone and mental well-being of patients.

Kidney transplantation does not increase the level of basic hope or life satisfaction compared with hemodialysis in patients with chronic kidney disease.

PubMed

Zegarow, P; Jankowska, M; Sańko-Resmer, J; Durlik, M; Grzeszczyk, M; Pączek, L

2014-10-01

Although renal replacement therapy can lead to improved health, it also can cause emotional disturbances in patients. It is believed that the success of renal replacement therapy hinges not only on medical parameters, but also on psychosocial factors, which is why modern medicine provides an ever-increasing role in the improvement of patients' quality of life. The purpose of this study was to compare the level of life satisfaction, purpose in life, and basic hope in patients who had received renal replacement due to chronic kidney disease. We also tested whether the specific type of renal replacement therapy and kidney function parameters were influential factors on the above variables. Sixty-one adult patients treated via renal replacement for chronic kidney disease took part in the study. Patients were divided into two groups: 31 hemodialysis patients (15 women and 16 men, ages 23-77 years, mean 51.19 years, SD 14.53 years) and 30 patients who had undergone kidney transplantation (14 women and 16 men, ages 22-69 years, mean 48.40 years, SD 12.64 years). The following research tools were used for analysis: Satisfaction With Life Scale (SWLS), Purpose in Life Test (PIL), and Basic Hope Inventory (BHI-12). There were no statistical differences in the level of satisfaction with life between hemodialysis patients and postkidney transplant patients. The results for the SWLS obtained from both groups fell within the normal range. The average SWLS for hemodialysis patients remained 20.61, SD = 5.79; for postkidney transplant patients, it was 22.57, SD = 5.16. The PIL level in the group of hemodialysis patients (101.5, SD = 15.64) was significantly lower than in the group of postkidney transplant patients (109.7, SD = 15.54). The average BHI-12 level was similar in both groups. The average BHI-12 result for hemodialysis patients was 29.00 (SD = 5.06), and for postkidney transplant patients 29.93 (SD = 3.55). The correlations between the psychological variables and selected biochemical parameters are worthy of particular attention. Among hemodialysis patients, there was an additional correlation between SWLS and hematocrit; whereas for postkidney transplant patients, there was an additional correlation of PIL and eGFR. Our data show that satisfaction with life and basic hope do not increase in patients after renal replacement therapy. The form of renal replacement therapy (hemodialysis or kidney transplantation) does not change the above variables. Patients treated via renal replacement require specialized psychological support to improve the efficacy of renal replacement therapy.

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

PubMed

Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

2015-03-01

Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively). This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

Successfully treated necrotizing fasciitis using extracorporeal life support combined with hemoadsorption device and continuous renal replacement therapy.

PubMed

Eid, Maroua; Fouquet, Olivier; Darreau, Cédric; Pierrot, Marc; Kouatchet, Achille; Mercat, Alain; Baufreton, Christophe

2018-03-01

Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device. A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb ® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run. During the days following CytoSorb ® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters. This case describes the successful use of CytoSorb ® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.

Impact of computerized order entry and pre-mixed dialysis solutions for continuous veno-venous hemodiafiltration on selection of therapy for acute renal failure.

PubMed

Saadulla, Lawand; Reeves, W Brian; Irey, Brittany; Ghahramani, Nasrollah

2012-02-01

To investigate the impacts of availability of pre-mixed solutions and computerized order entry on nephrologists' choice of the initial mode of renal replacement therapy in acute renal failure. We studied 898 patients with acute renal failure in 3 consecutive eras: era 1 (custom-mixed solution; n = 309), era 2 (pre-mixed commercial solution; n = 324), and era 3 (post-computerized order entry; n = 265). The proportion of patients treated with renal replacement therapy and the time from consult to initiation of continuous renal replacement therapy was similar in the 3 eras. Following introduction of the pre-mixed solution, the proportion of patients treated with continuous renal replacement therapy increased (20% vs. 33%; p < 0.05), it was initiated at a lower serum creatinine (353 ± 123 μmol/L vs. 300 ± 80 μmol/L; p < 0.05) and in older patients (53 ± 12 vs. 61 ± 14 years; p < 0.05). There was a progressive increase in the use of continuous veno-venous hemodialysis (18% vs. 79% vs. 100%; p < 0.05) and in the total prescribed flow rate (1,382 ± 546 vs. 2,324 ± 737 vs. 2,900 ± 305 mL/hr 3; p < 0.05). There was no significant impact on mortality. The availability of a pre-mixed solution increases the likelihood of initiating continuous renal replacement therapy in acute renal failure, initiating it at a lower creatinine and for older patients, use of continuous veno-venous hemodialysis and higher prescribed continuous renal replacement therapy dose. Computerized order entry implementation is associated with an additional increase in the use of continuous veno-venous hemodialysis, higher total prescribed dialysis dose, and use of CRRT among an increasing number of patients not on mechanical ventilation. The effect of these changes on patient survival is not significant.

European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

PubMed

Ekman, Bertil; Fitts, David; Marelli, Claudio; Murray, Robert D; Quinkler, Marcus; Zelissen, Pierre M J

2014-05-09

Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK and Sweden, with recruitment soon to be initiated in the Netherlands. EU-AIR will provide a unique opportunity not only to collect long-term safety data on a modified-release preparation of glucocorticoid but also to evaluate baseline data on conventional glucocorticoid replacement. Such data should help to improve the treatment of AI.

Recombinant human leptin in women with hypothalamic amenorrhea.

PubMed

Welt, Corrine K; Chan, Jean L; Bullen, John; Murphy, Robyn; Smith, Patricia; DePaoli, Alex M; Karalis, Aspasia; Mantzoros, Christos S

2004-09-02

Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (+/-SD) of 8.5+/-8.1 months. Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH levels and LH pulse frequency after two weeks and increased maximal follicular diameter, the number of dominant follicles, ovarian volume, and estradiol levels over a period of three months. Three patients had an ovulatory menstrual cycle (P<0.05 for the comparison with an expected rate of spontaneous ovulation of 10 percent); two others had preovulatory follicular development and withdrawal bleeding during treatment (P<0.05). Recombinant leptin significantly increased levels of free triiodothyronine, free thyroxine, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, bone alkaline phosphatase, and osteocalcin but not cortisol, corticotropin, or urinary N-telopeptide. Leptin administration for the relative leptin deficiency in women with hypothalamic amenorrhea appears to improve reproductive, thyroid, and growth hormone axes and markers of bone formation, suggesting that leptin, a peripheral signal reflecting the adequacy of energy stores, is required for normal reproductive and neuroendocrine function. Copyright 2004 Massachusetts Medical Society

The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage

PubMed Central

Kopczak, Anna; Krewer, Carmen; Schneider, Manfred; Kreitschmann-Andermahr, Ilonka; Schneider, Harald Jörn; Stalla, Günter Karl

2015-01-01

Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH) in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1) patients with lowered basal laboratory values; (2) patients with lowered basal laboratory values or the need for hormone replacement therapy; (3) diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients), lowered estradiol (14.3% of female patients) and lowered insulin-like growth factor I (IGF-I) values (12.1%) were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians’ diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery) were predominantly observed for the somatotropic axis (12.5%), the gonadotropic axis in women (11.1%) and the corticotropic axis (10.6%). Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004). In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4) values) to 94.6% (prolactin values). PMID:26703585

Development and Validation of a Simplified Renal Replacement Therapy Suitable for Prolonged Field Care in a Porcine (Sus scrofa) Model of Acute Kidney Injury

DTIC Science & Technology

2018-03-01

of a Simplified Renal Replacement Therapy Suitable for Prolonged Field Care in a Porcine (Sus scrofa) Model of Acute Kidney Injury. PRINCIPAL...and methods, results - include tables/figures, and conclusions/applications.) Objectives/Background: Acute kidney injury (AKI) is a serious

Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

PubMed Central

Sonnenschein, Carlos

2008-01-01

"The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

Diagnosis of hypogonadism: clinical assessments and laboratory tests.

PubMed

Carnegie, Christina

2004-01-01

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

Re-engineering Islet Cell Transplantation

PubMed Central

Fotino, Nicoletta; Fotino, Carmen; Pileggi, Antonello

2015-01-01

We are living exciting times in the field of beta cell replacement therapies for the treatment of diabetes. While steady progress has been recorded thus far in clinical islet transplantation, novel approaches are needed to make cell-based therapies more reproducible and leading to long-lasting success. The multiple facets of diabetes impose the need for a transdisciplinary approach to attain this goal, by targeting immunity, promoting engraftment and sustained functional potency. We discuss herein the emerging technologies applied to beta cell replacement therapies. PMID:25814189

The Effect of Thyroid Hormone, Prostaglandin E2, and Calcium Gluconate on Orthodontic Tooth Movement and Root Resorption in Rats

PubMed Central

Seifi, Massoud; Hamedi, Roya; Khavandegar, Zohre

2015-01-01

Statement of the Problem A major objective of investigators is to clarify the role of metabolites in achievement of maximum tooth movement with minimal root damage during orthodontic tooth movement (OTM). Purpose The aim of this study was to determine the effect of administration of thyroid hormone, prostaglandin E2, and calcium on orthodontic tooth movement and root resorption in rats. Materials and Method Sixty four male Wistar rats were randomly divided into 8 groups of eight rats each: 1- 20µg/kg thyroxine was injected in traperitoneally after installation of the orthodontic appliance.  2- 0.1 ml of 1 mg/ml prostaglandin E2 was injected submucosally.  3- 10% (200 mg/kg) calcium gluconate was injected.  4- Prostaglandin E2 was injected submucosally and 10% calcium was injected intraperitoneally.  5- Thyroxine was injected intraperitoneally and prostaglandin E2 was injected submucosally.  6- 20µg/kg thyroxine with calcium was injected. 7- Prostaglandin E2 was injected submucosally with calcium and thyroxine.  8- Distilled water was used in control group. The orthodontic appliances comprised of a NiTi closed coil were posteriorly connected to the right first molar and anteriorly to the upper right incisor. OTM was measured with a feeler gauge. The mid-mesial root of the first molar and the adjacent tissues were histologically evaluated. The Data were analyzed by one-way ANOVA and Student-Newman-Keuls test. Results The highest mean OTM was observed in the thyroxine and prostaglandin E2 group (Mean±SD = 0.7375±0.1359 mm) that was significantly different (p< 0.05). A significant difference (p< 0.05) in root resorption was observed between the prostaglandin E2 (0.0192±0.0198 mm2) and the other groups. Conclusion It seems that the combination of thyroxine and prostaglandin E2, with a synergistic effect, would decrease the root resorption and increase the rate of orthodontic tooth movement in rats. PMID:26106633

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.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

PubMed

Cangiano, B; Cacciatore, C; Persani, L; Bonomi, M

2017-01-01

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.

Endothelin mechanisms in altered thyroid states in the rat.

PubMed

Rebello, S; Thompson, E B; Gulati, A

1993-06-11

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

PubMed

Tillotson, S L; Fuggle, P W; Smith, I; Ades, A E; Grant, D B

1994-08-13

To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. 361 children with congenital hypothyroidism given early treatment and 315 control children. Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.

Rhabdomyolysis in a Young Girl with Van Wyk-Grumbach Syndrome due to Severe Hashimoto Thyroiditis.

PubMed

Leonardi, Alberto; Penta, Laura; Cofini, Marta; Lanciotti, Lucia; Principi, Nicola; Esposito, Susanna

2018-04-09

Background: Autoimmune hypothyroidism (Hashimoto thyroiditis; HT) is the most common postnatal thyroid disease. Clinical manifestations of HT vary according to disease severity. Due to the pleiotropic effects of thyroid hormone, less common signs and symptoms of HT can occur, leading to a delay in diagnosis. Case presentation: A 9-year-old girl of Indian origin was admitted for a one-week history of widespread myalgia, fatigue, muscle weakness, difficulty walking, and a significant increase in weight (approximately 2 kg) without any changes in daily habits. The only relevant medical history was several intermittent vaginal bleeding episodes since four years of age. Breast development was consistent with Tanner stage 2 without pubic or axillary hair; while height and weight were at the 10th percentile and the 38th percentile; respectively. Bone age from a left wrist X-ray was delayed 1 year. Pelvic ultrasonography revealed a uterine body/neck ratio of >1 (pubertal stage) and multifollicular ovaries. Her external genitalia had a childlike appearance. Laboratory examinations showed an increased thyroid-stimulating hormone, decreased free thyroxine, and positive anti-thyroglobulin antibody titres, as well as elevation of creatine phosphokinase, myoglobin, lactate dehydrogenase, serum aspartate aminotransferase, hypercholesterolemia, and a basal serum prolactin near the upper limit of normal. Follicle stimulating hormone and estradiol were slightly and significantly elevated, respectively. Thyroid ultrasound showed an increased gland size with irregular echostructures and high vascularization. Levothyroxine replacement therapy led to complete normalization of clinical and laboratory findings, including rhabdomyolysis indices. No further vaginal bleeding episodes were reported. Conclusion: This case report highlights how various can be the clinical picture of HT in children, and how rare clinical manifestations can be the only signs of disease at presentation leading to delayed diagnosis and treatment. In this girl, a never-described association of Van Wyk-Grumbach syndrome and acute rhabdomyolysis in a young girl with previously unrecognized HT is described. The importance of recognizing the signs and symptoms of rare complications of HT in order to begin appropriate therapy is stressed.

Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?

PubMed Central

Ip, David; Fu, Nga Yue

2015-01-01

Background This study evaluated whether half-yearly hyaluronic acid injection together with low-level laser therapy in addition to standard conventional physical therapy can successfully postpone the need for joint replacement surgery in elderly patients with bilateral symptomatic tricompartmental knee arthritis. Methods In this prospective, double-blind, placebo-controlled study, 70 consecutive unselected elderly patients with bilateral tricompartmental knee arthritis were assigned at random to either one of two conservative treatment protocols to either one of the painful knees. Protocol A consisted of conventional physical therapy plus a sham light source plus saline injection, and protocol B consisted of protocol A with addition of half-yearly hyaluronic acid injection as well as low-level laser treatment instead of using saline and a sham light source. Treatment failure was defined as breakthrough pain necessitating joint replacement. Results Among the 140 painful knees treated with either protocol A or protocol B, only one of the 70 painful knees treated by protocol B required joint replacement, whereas 15 of the 70 painful knees treated by protocol A needed joint replacement surgery (P<0.05). Conclusion We conclude that half-yearly hyaluronic acid injections together with low-level laser therapy should be incorporated into the standard conservative treatment protocol for symptomatic knee arthritis, because it may prolong the longevity of the knee joint without the need for joint replacement. PMID:26346122

Long-Term Adaptive Servo-Ventilator Treatment Prevents Cardiac Death and Improves Clinical Outcome.

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Komuro, Issei

2016-01-01

Adaptive servo-ventilation (ASV) is a recently developed, noninvasive therapeutic tool for the treatment of heart failure (HF). However, the efficacy of ASV therapy in patients with advanced HF remains uncertain, especially as regards its contribution to freedom from cardiac replacement therapy. A total of 85 patients with advanced HF (New York Heart Association [NYHA] class IV 71%, inotrope infusion-dependent 34%) refractory to guideline-directed medical therapy, received ASV therapy, irrespective of sleep-disordered breathing, at our institute between 2008 and 2014. Among these 85 patients, 46 continued ASV therapy for > 1 month (continued group), whereas 39 discontinued the therapy after < 1 month because of intolerance (discontinued group). There were no significant differences in baseline variables between the two groups. Heart rate indicating sympathetic activity, left ventricular (LV) reverse remodeling assessed by LV diastolic diameter, LV ejection fraction, and the grades of mitral and tricuspid regurgitations, HF severity assessed by NYHA class and plasma level of B-type natriuretic peptide, and end-organ dysfunction, improved significantly at 6 months following the initiation of ASV therapy (P < 0.05 for all). All-cause mortality and cardiac death rate were significantly lower during 2-year follow up in the continued group (P < 0.05 for both). In conclusion, ASV is a novel therapeutic tool prior to cardiac replacement therapy in patients with advanced HF and may prolong the period until cardiac replacement therapy becomes necessary.

[The application of electroacupuncture to postoperative rehabilitation of total knee replacement].

PubMed

Chen, Gang; Gu, Rui-Xin; Xu, Dan-Dan

2012-04-01

To explore the effect of electroacupuncture therapy for postoperative rehabilitation of total knee replacement of knee osteoarthritis. Seventy cases of total knee replacement of knee osteoarthritis were randomly divided into an acupuncture-rehabilitation group and a rehabilitation group, thirty five cases in each group. In acupuncture-rehabilitation group, routine rehabilitation therapy combined with electroacupuncture therapy was applied. The acupoints selection was mainly based on pathological location; Xuehai (SP 10), Liangqiu (ST 34), Dubi (ST 35), Neixiyan (EX-LE 4) and Yanglingquan (GB 34), etc. were selected. In rehabilitation group, routine rehabilitation therapy was applied. The functions of affected knee in both groups were evaluated by artificial total knee replacement scale of the New York Hospital for Special Surgery (HSS), range of motion (ROM) of affected knee, Visual Analogue Scale (VAS) of pain and Manual Muscle Test (MMT) before, and 2, 6 and 12 weeks after surgery. HSS scores in acupuncture-rehabilitation group were markedly higher than those in rehabilitation group in 2, 6 and 12 weeks after surgery (P < 0.05, P < 0.01); VAS scores in acupuncture-rehabilitation group were markedly lower than those in rehabilitation group (P < 0.05, P < 0.01); ROM and MMT in acupuncture-rehabilitation group were little superior to those in rehabilitation group, however, there was no significant difference (all P > 0.05). Rehabilitation therapy combined with electroacupuncture can obviously restrain the pain during rehabilitation process for total knee replacement patients, improve the endurance capacity of rehabilitation training and motivation, and obviously promote the recovery of total knee joint function.

[Correlations of central nervous system and thyroid function under chronic emotional stress].

PubMed

Amiragova, M G; Arkhangel'skaia, M I

1982-06-01

Experiments on cats exposed to chronic emotional stress induced during one week by 4-hour immobilization of the animals in conjunction with aperiodic electrocutaneous stimulation were made to study correlations of the time course of changes in the EEG of the cortical and subcortical structures and the content of thyroxin in the peripheral blood at varying time of the experiments. It was demonstrated that in the course of stress, the EEG manifests the cycles of "burst" activity of slow waves, which are first recorded in the posterior hypothalamus and then get generalized. This is accompanied by a significantly high thyroxin secretion. As the stress exposures are repeated, the EEG changes become dominant, also corresponding with high thyroxin secretion. After the experiments are over, the cycles of "burst" activity accompanied by enhanced thyroid function are still recordable over several days.

Hormone replacement therapy: short-term versus long-term use.

PubMed

Rousseau, Mary Ellen

2002-01-01

Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

Umbilical cord: an unlimited source of cells differentiable towards dopaminergic neurons

PubMed Central

Boroujeni, Mahdi Eskandarian; Gardaneh, Mossa

2017-01-01

Cell replacement therapy utilizing mesenchymal stem cells as its main resource holds great promise for ultimate treatment of human neurological disorders. Parkinson's disease (PD) is a common, chronic neurodegenerative disorder hallmarked by localized degeneration of a specific set of dopaminergic neurons within a midbrain sub-region. The specific cell type and confined location of degenerating neurons make cell replacement therapy ideal for PD treatment since it mainly requires replenishment of lost dopaminergic neurons with fresh and functional ones. Endogenous as well as exogenous cell sources have been identified as candidate targets for cell replacement therapy in PD. In this review, umbilical cord mesenchymal stem cells (UCMSCs) are discussed as they provide an inexpensive unlimited reservoir differentiable towards functional dopaminergic neurons that potentially lead to long-lasting behavioral recovery in PD patients. We also present miRNAs-mediated neuronal differentiation of UCMSCs. The UCMSCs bear a number of outstanding characteristics including their non-tumorigenic, low-immunogenic properties that make them ideal for cell replacement therapy purposes. Nevertheless, more investigations as well as controlled clinical trials are required to thoroughly confirm the efficacy of UCMSCs for therapeutic medical-grade applications in PD. PMID:28852404

Development of an accurate fluid management system for a pediatric continuous renal replacement therapy device

PubMed Central

SANTHANAKRISHNAN, ARVIND; NESTLE, TRENT T.; MOORE, BRIAN L.; YOGANATHAN, AJIT P.; PADEN, MATTHEW L.

2013-01-01

Acute kidney injury is common in critically ill children and renal replacement therapies provide a life saving therapy to a subset of these children. However, there is no Food and Drug Administration approved device to provide pediatric continuous renal replacement therapy (CRRT). Consequently, clinicians adapt approved adult CRRT devices for use in children due to lack of safer alternatives. Complications occur using adult CRRT devices in children due to inaccurate fluid balance (FB) between the volumes of ultrafiltrate (UF) removed and replacement fluid (RF) delivered. We demonstrate the design and validation of a pediatric fluid management system for obtaining accurate instantaneous and cumulative FB. Fluid transport was achieved via multiple novel pulsatile diaphragm pumps. The conservation of volume principle leveraging the physical property of fluid incompressibility along with mechanical coupling via a crankshaft was used for FB. Accuracy testing was conducted in vitro for 8-hour long continuous operation of the coupled UF and RF pumps. The mean cumulative FB error was <1% across filtration flows from 300 mL/hour to 3000 mL/hour. This approach of FB control in a pediatric specific CRRT device would represent a significant accuracy improvement over currently used clinical implementations. PMID:23644618

Induced pluripotent stem cells in Alzheimer's disease: applications for disease modeling and cell-replacement therapy.

PubMed

Yang, Juan; Li, Song; He, Xi-Biao; Cheng, Cheng; Le, Weidong

2016-05-17

Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

[Progress assessment of rehabilitation in patients after hip replacement. Preliminary report].

PubMed

Labecka, Monika; Pingot, Mariusz; Pingot, Julia; Woldańiska-Okońska, Marta

2014-01-01

Coxarthrosis is one of the most common diseases of the motor system. We distinguish primary and secondary coxarthrosis. The premises for total hip replacement include pain, damage to the surface of the acetabulum and the head of the hip, relative shortening of the limb, gluteal, femur and crus muscle atrophy and gait dysfunctions. The aim of this paper is to present the influence of rehabilitation on the improvement of physical ability, especially in respect to quality of gait and antianalgesic efficacy of the physical therapy in patients after total hip replacement. The study was carried out in 37 patients aged 35-72 (mean of age--53.78 +/- 9.92). The group consisted'of 21 women and 16 men. After the total hip replacement, all the patients underwent physical therapy which involved application of laser radiation on the postoperative scar, whirpool and classic massage of the operated limb, exercises in non-weight bearing and weight-bearing exercises and gait reeducation. Modified Laitinen Pain Indicator Questionnaire, Visual Analogue Scale-VAS and the standardized mobility test--Timed-Up-And-Go test were used in the study. The statistical analysis was carried out with the use of the STATYSTIKA 5 PL computer program. The results reached point to the analgesic efficacy of the physical therapy and a better gait quality. Multifactor physical therapy after total hip replacement shows analgesic action. Appropriate selection of exercises and physical treatment have positive influence on gait reeducation in patients after total hip replacement. The Timed Up and Go test may be used in functional assessment of gait in patients with musculoskeletal disorders.

Physician trust and depression influence adherence to factor replacement: a single-centre cross-sectional study.

PubMed

Tran, D Q; Barry, V; Antun, A; Ribeiro, M; Stein, S; Kempton, C L

2017-01-01

Poor adherence to factor replacement therapy among patients with haemophilia can lead to joint bleeding and eventual disability. The aim of this study was to determine patient-related characteristics associated with adherence to factor replacement in adults with haemophilia. Adults with haemophilia were recruited to participate in this cross-sectional study. Adherence was measured using either the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)-Pro or the VERITAS-PRN questionnaire. Simple and multiple regression analyses that controlled for confounding were performed to determine the association between patient-related characteristics and adherence to factor replacement therapy. Of the 99 subjects enrolled, all were men; 91% had haemophilia A and 78% had severe disease. Age ranged from 18 to 62 years. Most (95%) had functional health literacy; but only 23% were numerate. Mean adherence scores were 45.6 (SD 18) and 51.0 (SD 15) for those on a prophylactic and those on an episodic regimen, respectively, with a lower score indicating better adherence. On multivariable analysis, being on any chronic medication, longer duration followed at our haemophilia treatment centre, higher physician trust and better quality of life were associated with higher adherence. A history of depression was associated with lower adherence. Two potentially modifiable characteristics, physician trust and depression, were identified as motivator and barrier to adherence to factor replacement therapy. Promoting a high level of trust between the patient and the healthcare team as well as identifying and treating depression may impact adherence to factor replacement therapy and accordingly reduce joint destruction. © 2016 John Wiley & Sons Ltd.

Therapeutic avenues for hereditary forms of retinal blindness.

PubMed

Kannabiran, Chitra; Mariappan, Indumathi

2018-03-01

Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one or more genes that lead to the death of the retinal photoreceptor cells. Till date, mutations in over 200 genes are known to be associated with all different forms of retinal disorders. The enormous genetic heterogeneity of this group of diseases has posedmany challenges in understanding the mechanisms of disease and in developing suitable therapies. Therapeutic avenues that are being investigated for these disorders include gene therapy to replace the defective gene, treatment with neurotrophic factors to stimulate the growth of photoreceptors, cell replacement therapy, and prosthetic devices that can capture light and transmit electrical signals through retinal neurons to the brain. Several of these are in process of human trials in patients, and have shown safety and efficacy of the treatment. A combination of approaches that involve both gene replacement and cell replacement may be required for optimum benefit.

Radioiodine therapy in patients with Graves' disease and the effects of prior carbimazole therapy.

PubMed

Karyampudi, Arun; Hamide, Abdoul; Halanaik, Dhanapathi; Sahoo, Jaya Prakash; Kamalanathan, Sadishkumar

2014-09-01

The use of radioiodine as the first line of treatment in Graves' disease is restricted in India because of its limited availability and an unrealistic risk perception associated with it. Additionally, the effectiveness of radioiodine ablation in Graves' disease is influenced by many factors. Prior medical antithyroid therapy is one such important factor. To analyze the efficacy of low dose radioiodine therapy (5 mCi) in treatment of naive patients of Graves' disease in comparison to that in which it was already primed with an antithyroid drug, carbimazole. A non-randomized, interventional study conducted in the Department of Medicine and Endocrinology of a tertiary care institute in South India. The study had two groups; Group A (36 treatment naive, uncomplicated Graves' disease patients) and B (34 Graves' disease patients on carbimazole prior to radioiodine therapy). Both groups had baseline clinical, biochemical evaluation and were reassessed at 3 and 6 months for evaluating the clinical status for possible documentation of cure. The cure rate was 61.1% in drug naive group and 58.8% in pretreated group at 6 months following radioiodine (P = 0.845). Higher baseline 999m technicium (99m Tc) uptake, male gender, BMI and higher baseline free thyroxine (fT4) level predicted treatment failure following radioiodine therapy. Administration of carbimazole prior to low dose radioiodine therapy does not alter the efficacy of radioiodine. Low fixed dose (5 mCi) of radioactive iodine may be a safe and effective primary therapeutic option in Graves' disease patients pretreated with antithyroid drugs.

BDE 47 AND PCB 153 INCREASE THYROXINE CATABOLISM IN PRIMARY RAT AND HUMAN HEPATOCYTES: THE UTILITY OF HEPATOCYTES AS SCREENING TOOLS FOR POTENTIAL THYROID HORMONE DISRUPTORS

EPA Science Inventory

Studies demonstrate that exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) and 2,2',4,4',5,5'· hexachlorobiphenyl (PCB 153) decrease serum thyroxine (T4)levels in laboratory animals 1,2,3. The T4 decrease in rodents is thought to occur through the induction of UDP-glucurono...

Thyrotoxicosis in a dog induced by the consumption of feces from a levothyroxine-supplemented housemate

PubMed Central

Shadwick, Steven R.; Ridgway, Marcella D.; Kubier, Amy

2013-01-01

A 9-year-old golden retriever dog was evaluated for polyuria, polydipsia, weight loss, and elevated serum thyroxine. Targeted questioning revealed that the dog was coprophagic and routinely ingested the feces of a dog that was treated with twice-daily levothyroxine. Clinical signs resolved and serum thyroxine decreased to normal levels in the affected dog with prevention of coprophagy. PMID:24155422

Thermal stability of synthetic thyroid hormone l-thyroxine and l-thyroxine sodium salt hydrate both pure and in pharmaceutical formulations.

PubMed

Ledeţi, Ionuţ; Ledeţi, Adriana; Vlase, Gabriela; Vlase, Titus; Matusz, Petru; Bercean, Vasile; Şuta, Lenuţa-Maria; Piciu, Doina

2016-06-05

In this paper, the thermal stability of pure l-thyroxine (THY) and l-thyroxine sodium salt hydrate (THYSS) vs. two pharmaceutical solid formulations commercialized on both Romanian and European market (with a content of 100μg, respectively 200μg THYSS per tablet) were investigated. In order to determine whether the presence of excipients affects the thermal stability of the active pharmaceutical ingredient (API), the preliminary study of thermal stability in air atmosphere was completed with an in-depth solid-state kinetic study. By kinetic analysis, the non-isothermal degradation of the selected active pharmaceutical ingredients vs. the solid formulation with strength of 200μg THYSS per tablet was investigated. Isoconversional methods (Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa and Friedman) were employed for the estimation of activation energies values, at five different heating rates, β=5, 7, 10, 12 and 15°Cmin(-1). Also, a fourth method was applied in the processing of data, namely NPK, allowing an objective separation in the physical and chemical processes that contribute to the thermal degradation of the selected compounds. A discussion of thermal stability from the kinetic point of view is also presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Radioimmunoassay of ''free thyroxin'' in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects

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

Mizuta, H.; Miyai, K.; Ichihara, K.

1982-03-01

In this sensitive, simple method for measuring ''free thyroxin'' (FT/sub 4/) in eluates of dried blood spots on filter paper by use of a radioimmunoassay kit (Amerlex Free T/sub 4/ RIA), the measurable range of FT/sub 4/ is 1.8 to 57 ng/L (equivalent to the concentration in serum), or 7 to 237 fg/tube. The mean coefficients of variation for within assay-within spots, within assay-between spots, and between assays were 5.3%, 5.0%, and 6.2%, respectively. FT/sub 4/ in blood spotted on filter paper is stable for at least a month when dried and kept at either -20/sup 0/C, 4/sup 0/C, roommore » temperature (about 25/sup 0/C), or 37/sup 0/C. The results for FT/sub 4/ in dried blood spots correlated closely with the free-T/sub 4/ concentration in serum (r = 0.99). The method can be used to differentiate cases of primary and secondary hypothyroidism from normal subjects and those with subnormal thyroxin-binding globulin. This method may be useful in screening for congenital hypothyroidism, because sample-retesting is not necessary.« less

Structural and functional maturation of rat gastrointestinal barrier with thyroxine

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

Israel, E.J.; Pang, K.Y.; Harmatz, P.R.

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed in rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activitymore » of treated animals (T) was 1.5-2 times less than that of controls (C), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased, while the K/sub a/ remained the same, demonstrating the functional maturation of the MVM. In conclusion, thryoid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.« less

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer

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

Chan, D.W.; Waud, J.M.; Hsu, T.H.

1983-06-01

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T4 derivative that does not bind significantly to the thyroxine-binding proteins. We evaluated this RIA for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T4 assay, expressed as coefficient of variation, was 20% at 0.16 ng/dl, 6.9% at 0.55 ng/dl, 4.2% at 1.08 ng/dl, 5.3% at 2.29 ng/dl, and 6.3% at 3.18 ng/dl. A reference range for free T4 was established as 0.68-1.8 ng/dl, n . 171. The correlation coefficients (r) of a dialysis methodmore » and a free thyroxine index were 0.871 and 0.911, respectively. Free T4 correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition, 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T4, very low T3, and elevated rT3. We found this free T4 assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.« less

Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

PubMed

Martí-Carbonell, Maria Assumpció; Garau, Adriana; Sala-Roca, Josefina; Balada, Ferran

2012-01-01

Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Update on role of agalsidase alfa in management of Fabry disease

PubMed Central

Ramaswami, Uma

2011-01-01

Fabry disease (FD) is an X-linked lysosomal storage disorder that affects both men and women. The manifestations of this heterogeneous disease are multisystemic and progressive. Prior to the development of enzyme replacement therapy, the management and treatment for Fabry disease was largely nonspecific and supportive. Because enzyme replacement therapy became commercially available in 2001, a variety of clinical benefits in Fabry patients have been consistently reported, including improved renal pathology and cardiac function, and reduced severity of neuropathic pain and improved pain-related quality of life. This update focuses on published data on the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa, and gives a brief overview on some of the outstanding management issues in the treatment of this complex disease. PMID:21552486

From Cholera to Burns: A Role for Oral Rehydration Therapy

PubMed Central

Green, W.B.; Asuku, M.E.; Feldman, M.; Makam, R.; Noppenberger, D.; Price, L.A.; Prosciak, M.; van Loon, I.N.

2011-01-01

According to the practice guidelines of the American Burn Association on burn shock resuscitation, intravenous (IV) fluid therapy is the standard of care for the replacement of fluid and electrolyte losses in burn injury of ≥20% of the total body surface area. However, in mass burn casualties, IV fluid resuscitation may be delayed or unavailable. Oral rehydration therapy (ORT), which has been shown to be highly effective in the treatment of dehydration in epidemics of cholera, could be an alternate way to replace fluid losses in burns. A prospective case series of three patients was carried out as an initial step to establish whether oral Ceralyte®90 could replace fluid losses requiring IV fluid therapy in thermal injury. The requirement of the continuing IV fluid therapy was reduced by an average of 58% in the first 24 hours after the injury (range 37-78%). ORT may be a feasible alternative to IV fluid therapy in the resuscitation of burns. It could also potentially save many lives in mass casualty situations or in resource-poor settings where IV fluid therapy is not immediately available. Further studies are needed to assess the efficacy of this treatment and to determine whether the present formulations of ORT for cholera need modification. PMID:22283039

Genes and Gene Therapy

MedlinePlus

... a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

Anesthetic Considerations for Transcatheter Pulmonary Valve Replacement.

PubMed

Gregory, Stephen H; Zoller, Jonathan K; Shahanavaz, Shabana; Chilson, Kelly L; Ridley, Clare H

2018-02-01

The introduction of transcatheter therapy for valvular heart disease has revolutionized the care of patients with valvular disorders. Pathologic regurgitation or stenosis of the pulmonary valve, right ventricular outflow tract, or a right ventricle-to-pulmonary artery conduit represent emerging indications for transcatheter therapy. To date, minimal literature exists detailing the anesthetic management of patients undergoing transcatheter pulmonary valve replacement. In this review, the pathophysiology and indications for transcatheter pulmonary valve replacement and possible complications unique to this procedure are reviewed. Anesthetic management, including preoperative assessment, intraoperative considerations, and early postoperative monitoring, are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Meta-Analysis of the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: Differences between Men and Women

ERIC Educational Resources Information Center

Cepeda-Benito, Antonio; Reynoso, Jose T.; Erath, Stephen

2004-01-01

Gender differences in the efficacy of nicotine replacement therapies (NRTs) were examined in a meta-analytical review of 90 effect sizes obtained from a sample of 21 double-blind, placebo-controlled randomized studies. Although NRT was more effective for men than placebo at 3-month, 6-month, and 12-month follow-ups, the benefits of NRT for women…

[Lung and kidney failure. Pathogenesis, interactions, and therapy].

PubMed

John, S; Willam, C

2015-09-01

The lungs and kidneys represent the most often affected organs (acute respiratory distress syndrome, ARDS or kidney failure) in multiple organ failure (MOF) due to shock, trauma, or sepsis with a still unacceptable high mortality for both organ failures. Although the exact pathophysiological mechanisms of MOF are not completely elucidated, it appears that the lungs and kidneys share several pathophysiologic pathways and have the potential to further harm each other (kidney-lung crosstalk). Inflammatory signals in both directions and volume overload with consecutive edema formation in both organs may play a key role in this crosstalk. The organ replacement therapies used in both organ failures have the potential to further injure the other organ (ventilator trauma, dialyte trauma). On the other hand, renal replacement therapy can have positive effects on lung injury by restoring volume and acid-base homeostasis. The new development of "low-flow" extracorporeal CO2 removal on renal replacement therapy platforms may further help to decrease ventilator trauma in the future.

ESTROGEN REPLACEMENT THERAPY INDUCES FUNCTIONAL ASYMMETRY ON AN ODOR MEMORY/DISCRIMINATION TEST

PubMed Central

Doty, Richard L.; Kisat, Mehreen; Tourbier, Isabelle

2008-01-01

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes. PMID:18466883

Effectiveness of Occupational Therapy Interventions for Lower-Extremity Musculoskeletal Disorders: A Systematic Review.

PubMed

Dorsey, Julie; Bradshaw, Michelle

Lower-extremity (LE) musculoskeletal disorders (MSDs) can have a major impact on the ability to carry out daily activities. The effectiveness of interventions must be examined to enable occupational therapy practitioners to deliver the most appropriate services. This systematic review examined the literature published between 1995 and July 2014 that investigated the effectiveness of occupational therapy interventions for LE MSDs. Forty-three articles met the criteria and were reviewed. Occupational therapy interventions varied on the basis of population subgroup: hip fracture, LE joint replacement, LE amputation or limb loss, and nonsurgical osteoarthritis and pain. The results indicate an overall strong role for occupational therapy in treating clients with LE MSDs. Activity pacing is an effective intervention for nonsurgical LE MSDs, and multidisciplinary rehabilitation is effective for LE joint replacement and amputation. Further research on specific occupational therapy interventions in this important area is needed. Copyright © 2017 by the American Occupational Therapy Association, Inc.

[Genetic basis of head and neck cancers and gene therapy].

PubMed

Özel, Halil Erdem; Özkırış, Mahmut; Gencer, Zeliha Kapusuz; Saydam, Levent

2013-01-01

Surgery and combinations of traditional treatments are not successful enough particularly for advanced stage head and neck cancer. The major disadvantages of chemotherapy and radiation therapy are the lack of specificity for the target tissue and toxicity to the patient. As a result, gene therapy may offer a more specific approach. The aim of gene therapy is to present therapeutic genes into cancer cells which selectively eliminate malignant cells with no systemic toxicity to the patient. This article reviews the genetic basis of head and neck cancers and important concepts in cancer gene therapy: (i) inhibition of oncogenes; (ii) tumor suppressor gene replacement; (iii) regulation of immune response against malignant cells; (iv) genetic prodrug activation; and (v) antiangiogenic gene therapy. Currently, gene therapy is not sufficient to replace the traditional treatments of head and neck cancers, however there is no doubt that it will have an important role in the near future.

A review on hyperthyroidism: thyrotoxicosis under surveillance.

PubMed

Mansourian, Azad Reza

2010-11-15

Thyrotoxicosis exhibit collective clinical manifestation, caused by excessive serum thyroid hormones particularity thyroxin. The clinical signs and symptoms included general alteration of metabolic process leading to weight loss fatigue and weakness and some specific disorders such as cardiovascular, neuromuscular reproductive gastrointestinal dermatological and bone disorders. The diagnosis of thyrotoxicosis relay on the thyroid function test carried out by the laboratory serum measurement of thyroxin, triiodothyronine and thyroid stimulating hormones accompanied by other para-medical examinations suggested by clinicians and endociologicst. In thyrotoxicosis serum level of thyroid hormones and thyroxin in particular elevated accompanied by pituitary thyroid stimulating hormone suppression reaching to undetectable level in sever thyrotoxicosis. Among the most common cause of thyrotoxicosis are, thyroid autoimmunity diseases thyroid toxic, adenoma toxic nodular and multinodular hyperthyroidism. The main aim behind this review is to explore the clinical manifestation, the causative factors, diagnosis, metabolic disorder occur due to thyrotoxicosis.

Vibrational studies of Thyroxine hormone: Comparative study with quantum chemical calculations

NASA Astrophysics Data System (ADS)

Borah, Mukunda Madhab; Devi, Th. Gomti

2017-11-01

The FTIR and Raman techniques have been used to record spectra of Thyroxine. The stable geometrical parameters and vibrational wave numbers were calculated based on potential energy distribution (PED) using vibrational energy distribution analysis (VEDA) program. The vibrational energies are assigned to monomer, chain dimer and cyclic dimers of this molecule using the basis set B3LYP/LANL2DZ. The computational scaled frequencies are in good agreements with the experimental results. The study is extended to calculate the HOMO-LUMO energy gap, Molecular Electrostatic Potential (MEP) surface, hardness (η), chemical potential (μ), Global electrophilicity index (ω) and different thermo dynamical properties of Thyroxine in different states. The calculated HOMO-LUMO energies show the charge transfer occurs within the molecule. The calculated Natural bond orbital (NBO) analysis confirms the presence of intra-molecular charge transfer as well as the hydrogen bonding interaction.

Thyroid effects of iodine and iodide in potable water

NASA Technical Reports Server (NTRS)

Bull, Richard J.; Thrall, Karla D.; Sherer, Todd T.

1991-01-01

Experiments are reviewed which examine the comparative toxicological effects of iodide (I) and iodine (I2) when used to disinfect drinking water. References are made to a subchronic study in rats, a comparison of the distribution of radiolabeled I and I2, and a demonstration of thyroxine formation in the gastrointestinal tract. The results of the study of the rats are examined in detail; the findings show that I and I2 have opposite effects on the concentrations of thyroid hormones in blood. Iodide slightly decreases circulating thyroxine, while I2 significantly increases the thyroxine concentrations, decreases triiodothyronine levels, and does not change the weight of the thyroid gland. The related effects of I2 ingestion are set forth in detail and are shown to be unique to I2 contamination. Iodine can counteract the effects of iodide and should therefore be used as a disinfectant in drinking water.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

PubMed Central

GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors

PubMed Central

Biegstraaten, Marieke; Hughes, Derralynn A.; Mehta, Atul; Elliott, Perry M.; Oder, Daniel; Watkinson, Oliver T.; Vaz, Frédéric M.; van Kuilenburg, André B. P.; Wanner, Christoph; Hollak, Carla E. M.

2017-01-01

Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension. PMID:28763515

Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.

PubMed

Haussmann, Ursula; Fischer, Joachim; Eber, Stefan; Scherer, Franziska; Seger, Reinhard; Gungor, Tayfun

2006-06-01

Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (< or =70%). If VOD was diagnosed clinically (according to modified Seattle criteria), high dose defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.

Efficacy of surfactant at different gestational ages for infants with respiratory distress syndrome

PubMed Central

Wang, Li; Chen, Long; Li, Renjun; Zhao, Jinning; Wu, Xiushuang; Li, Xue; Shi, Yuan

2015-01-01

Since exogenous surfactant replacement therapy was first used to prevent respiratory distress syndrome (RDS), it has become the main method for treatment of RDS. However, in some infants, death is inevitable despite intensive care and surfactant replacement therapy, especially in near-term and term infants. The main purpose of this study was to compare the therapeutic effect of pulmonary surfactant for infants at different gestational ages and to investigate whether exogenous surfactant replacement therapy is effective for all newborns with RDS. Data on surfactant replacement therapy, including blood gas, oxygenation function parameters and therapy results, were collected from 135 infants who were diagnosed with RDS during three years at a tertiary neonatal intensive care unit. According to gestational age, the subjects were classified into three groups as follows: group 1: gestational age <35 weeks (n=54); group 2: 35 weeks ≤ gestational age <37 weeks (n=35); group 3: gestational age ≥37 weeks (n=46). Six hours after surfactant was given, there were significantly better blood gas results in group 1 and worse results in groups 2 and 3. Similar oxygenation function parameter results were observed in the three groups. In addition, there was a trend toward an increased rate of repeated surfactant administration with increasing gestational age. For near-term and term infants, the efficacy of surfactant therapy was not as good as it was for preterm infants. The causes of RDS in near-term and term infants might be different from those in preterm infants and should be studied further. PMID:26550326

Dose determinants in continuous renal replacement therapy.

PubMed

Clark, William R; Turk, Joseph E; Kraus, Michael A; Gao, Dayong

2003-09-01

Increasing attention is being paid to quantifying the dose of dialysis prescribed and delivered to critically ill patients with acute renal failure (ARF). Recent trials in both the intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) realms have suggested that a direct relationship between dose and survival exists for both of these therapies. The purpose of this review, first, is to analyze critically the above-mentioned dose/outcome studies in acute dialysis. Subsequently, the factors influencing dose prescription and delivery are discussed, with the focus on continuous venovenous hemofiltration (CVVH). Specifically, differences between postdilution and predilution CVVH will be highlighted, and the importance of blood flow rate in dose delivery for these therapies will be discussed.

Low mood and response to Levothyroxine treatment in Indian patients with subclinical hypothyroidism.

PubMed

Vishnoi, Gaurav; Chakraborty, Baidarbhi; Garda, Hormaz; Gowda, Srinivas H; Goswami, Binita

2014-04-01

There is considerable controversy regarding the association of subclinical hypothyrodism (SCH) and depression. We studied the association of SCH with low mood and also investigated the effects of L-thyroxine (LT4) therapy on improvement of symptoms. Three hundred patients with SCH and 300 age and sex-matched healthy controls were studied. Serum levels of TSH, FT3, FT4 were measured by chemi-illuminescence. Hamilton Depression Rating Scale (HAM-D) was used to evaluate baseline depression in all participants and subsequently, in 133 patients who had undergone LT4 therapy for 2 months. The HAM-D scores were significantly higher for cases (10.0±4.7) as compared to controls (2.4±1.5). A positive correlation (r(2)=0.87, p=0.00) was found, between the Hamilton scores and serum TSH levels. No such association was seen between serum FT3, FT4 levels and HAM-D scores. Levothyroxine treatment resulted in a significant decrease in TSH levels and Hamilton scores. SCH is associated with low mood and there is a positive correlation between serum TSH levels and HAM-D scores. The administration of Levothyroxine therapy is associated with significant improvement in HAM-D scores. This underlines the importance of thyroid screening in cases of low mood and also asserts the role of Levothyroxine therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Childhood Thyroid Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood thyroid cancer treatment usually includes surgery and may include radioactive iodine therapy, targeted therapy, and hormone replacement therapy. Learn more about the diagnosis and treatment of childhood thyroid cancer in this expert-reviewed summary.

Effects of thyroid hormone manipulation on pre-nuptial molt, luteinizing hormone and testicular growth in male white-crowned sparrows (Zonotrichia leuchophrys gambelii).

PubMed

Pérez, Jonathan H; Meddle, Simone L; Wingfield, John C; Ramenofsky, Marilyn

2018-01-01

Most seasonal species rely on the annual change in day length as the primary cue to appropriately time major spring events such as pre-nuptial molt and breeding. Thyroid hormones are thought to be involved in the regulation of both of these spring life history stages. Here we investigated the effects of chemical inhibition of thyroid hormone production using methimazole, subsequently coupled with either triiodothyronine (T3) or thyroxine (T4) replacement, on the photostimulation of pre-nuptial molt and breeding in Gambel's white-crowned sparrows (Zonotrichia leuchophrys gambelii). Suppression of thyroid hormones completely prevented pre-nuptial molt, while both T3 and T4 treatment restored normal patterns of molt in thyroid hormone-suppressed birds. Testicular recrudescence was blocked by methimazole, and restored by T4 but not T3, in contrast to previous findings demonstrating central action of T3 in the photostimulation of breeding. Methimazole and replacement treatments elevated plasma luteinizing hormone levels compared to controls. These data are partially consistent with existing theories on the role of thyroid hormones in the photostimulation of breeding, while highlighting the possibility of additional feedback pathways. Thus we suggest that regulation of the hypothalamic pituitary gonad axis that controls breeding may be more complex than previously considered. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Rapid purification of tri-iodothyronine and thyroxine protein conjugates for antibody production.

PubMed

Burke, C W; Shakespear, R A

1975-04-01

Thyroxine (T-4) and tri-iodothyronine (T-3) were coupled to human serum albumin (HSA) with carbodi-imide. By adsorption chromatography on Sephadex G-25, fractions containing purified conjugate, but not reversibly-bound T-3 or T-4, were obtained, and this procedure took 5 h; considerably less than the conventional dialysis technique. Highly specific high-titre antisera were produced in rabbits and guinea-pigs by injection of these fractions in Freund's adjuvant.

[Hormone content of the blood plasma of rats after a flight on the Kosmos-1129 biosatellite].

PubMed

Tigranian, R A; Kalita, N F; Macho, L; Kvetnanský, R

1985-01-01

The concentration of ACTH, insulin, glucagon, glucose, epinephrine, norepinephrine, thyrotrophic hormone, thyroxine, and triiodothyronine was measured in plasma of the rats flown for 18.5 days on Cosmos-1129. As a result of the flight, the concentration of insulin, thyrotrophic hormone, and triiodothyronine increased and that of thyroxine decreased. It is suggested that the above changes have been induced by an acute stress associated with biosatellite reentry and touchdown.

Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs.

PubMed

Gołyński, M; Lutnicki, K; Krumrych, W; Szczepanik, M; Gołyńska, M; Wilkołek, P; Adamek, Ł; Sitkowski, Ł; Kurek, Ł

2017-09-01

Both elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders. The aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4). Ten healthy and 19 hypothyroid client-owned dogs. Dogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated. Hypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50-37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54-26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00-16.65 and 30.68 nmol/L; range, 22.84-38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = -0.47, P < 0.001), total thyroxine (ρ = -0.69, P = 0.0092), and free thyroxine (ρ = -0.56, P = 0.0302). Hypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Hypothyroidism in the elderly: diagnosis and management

PubMed Central

Bensenor, Isabela M; Olmos, Rodrigo D; Lotufo, Paulo A

2012-01-01

Thyroid disorders are highly prevalent, occurring most frequently in aging women. Thyroid-associated symptoms are very similar to symptoms of the aging process; thus, improved methods for diagnosing overt and subclinical hypothyroidism in elderly people are crucial. Thyrotropin measurement is considered to be the main test for detecting hypothyroidism. Combined evaluations of thyroid stimulating hormone (TSH) and free-thyroxine can detect overt hypothyroidism (high TSH with low free-thyroxine levels) and subclinical hypothyroidism (high TSH with normal free-thyroxine levels). It is difficult to confirm the diagnosis of thyroid diseases based only on symptoms, but presence of symptoms could be an indicator of who should be evaluated for thyroid function. The most important reasons to treat overt hypothyroidism are to relieve symptoms and avoid progression to myxedema. Overt hypothyroidism is classically treated using L-thyroxine; elderly patients require a low initial dose that is increased every 4 to 6 weeks until normalization of TSH levels. After stabilization, TSH levels are monitored yearly. There is no doubt about the indication for treatment of overt hypothyroidism, but indications for treatment of subclinical disease are controversial. Although treatment of subclinical hypothyroidism may result in lipid profile improvement, there is no evidence that this improvement is associated with decreased cardiovascular or all-cause mortality in elderly patients. In patients with a high risk of progression from subclinical to overt disease, close monitoring of thyroid function could be the best option. PMID:22573936

Endogenous thyroid hormone synthesis in facultative planktotrophic larvae of the sand dollar Clypeaster rosaceus: implications for the evolutionary loss of larval feeding.

PubMed

Heyland, Andreas; Reitzel, Adam M; Price, David A; Moroz, Leonid L

2006-01-01

Critical roles of hormones in metamorphic life history transitions are well documented in amphibians, lampreys, insects, and many plant species. Recent evidence suggests that thyroid hormones (TH) or TH-like compounds can regulate development to metamorphosis in echinoids (sea urchins, sand dollars, and their relatives). Moreover, previous research has provided evidence for endogenous hormone synthesis in both feeding and nonfeeding echinoderm larvae. However, the mechanisms for endogenous synthesis remain largely unknown. Here, we show that facultatively planktotrophic larvae (larvae that reach metamorphosis in the absence of food but have the ability to feed) from the subtropical sea biscuit Clypeaster rosaceus can synthesize thyroxine endogenously from incorporated iodine (I(125)). When treated with the goitrogen thiourea (a peroxidase inhibitor), iodine incorporation, thyroxine synthesis, and metamorphosis are all blocked in a dose-dependent manner. The inhibitory effect on metamorphosis can be rescued by administration of exogenous thyroxine. Finally, we demonstrate that thiourea induces morphological changes in feeding structures comparable to the phenotypic plastic response of larval structures to low food conditions, further supporting a signaling role of thyroxine in regulating larval morphogenesis and phenotypic plasticity. We conclude that upregulation of endogenous hormone synthesis might have been associated with the evolution of nonfeeding development, subsequently leading to morphological changes characteristic of nonfeeding development.

Endogenous thyroid hormone synthesis in facultative planktotrophic larvae of the sand dollar Clypeaster rosaceus: implications for the evolutionary loss of larval feeding

PubMed Central

Heyland, Andreas; Reitzel, Adam M.; Price, David A.; Moroz, Leonid L.

2014-01-01

SUMMARY Critical roles of hormones in metamorphic life history transitions are well documented in amphibians, lampreys, insects, and many plant species. Recent evidence suggests that thyroid hormones (TH) or TH-like compounds can regulate development to metamorphosis in echinoids (sea urchins, sand dollars, and their relatives). Moreover, previous research has provided evidence for endogenous hormone synthesis in both feeding and nonfeeding echinoderm larvae. However, the mechanisms for endogenous synthesis remain largely unknown. Here, we show that facultatively planktotrophic larvae (larvae that reach metamorphosis in the absence of food but have the ability to feed) from the subtropical sea biscuit Clypeaster rosaceus can synthesize thyroxine endogenously from incorporated iodine (I125). When treated with the goitrogen thiourea (a peroxidase inhibitor), iodine incorporation, thyroxine synthesis, and metamorphosis are all blocked in a dose-dependent manner. The inhibitory effect on metamorphosis can be rescued by administration of exogenous thyroxine. Finally, we demonstrate that thiourea induces morphological changes in feeding structures comparable to the phenotypic plastic response of larval structures to low food conditions, further supporting a signaling role of thyroxine in regulating larval morphogenesis and phenotypic plasticity. We conclude that upregulation of endogenous hormone synthesis might have been associated with the evolution of nonfeeding development, subsequently leading to morphological changes characteristic of nonfeeding development. PMID:17073939

Thyroxine-induced changes in the glycosylation pattern and in brain and serum levels of rat alpha-fetoprotein.

PubMed

Naval, J; Calvo, M; Lampreave, F; Piñeiro, A

1986-01-01

We have studied the effect of thyroid disfunction during the postnatal period, on the serum and brain levels of rat alpha-fetoprotein (AFP) and albumin. Hypothyroidism was induced by treatment of pregnant rats and their newborn pups with 2-mercapto-1-methylimidazole(methimazole). Hyperthyroidism was provoked in newborns by daily injections of thyroxine (0.25 micrograms/g body wt) from the 3rd postnatal day weaning. Impaired growth, lower brain size, altered behaviour and morphological features observed were according to an altered thyroid status. Hypothyroid rats showed a significantly reduction in serum AFP concentration (78% of control values at 8 days of age) and a slight increase in that of albumin. level could be appreciated. Thyroxine supplementation (0.2 micrograms/rat/day) corrected most of these alterations. Hyperthyroidism induced a drastic fall in both serum and brain AFP levels (about 48% of the corresponding control values). Albumin concentration in serum was augmented significantly from the 12th postnatal day, but its brain levels did not change significantly. In hyperthyroid rats, a significant reduction (37% relative to controls) in the concanavalin A-non reactive microform of AFP, was observed. This alteration of the glycosylation pattern of AFP could be due to the inhibition by thyroxine of the activity of the hepatic enzyme GlcNAc-transferase III.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

PubMed

Somaraju, Usha Rani; Solis-Moya, Arturo

2014-10-13

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 14 August 2014.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 12 May 2014. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 11 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 426 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67, P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, abdominal pain and fecal fat excretion. Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency. There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

A cost-effectiveness analysis of hormone replacement therapy in the menopause.

PubMed

Cheung, A P; Wren, B G

1992-03-02

To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone use and the treatment duration.

Ogilvie's syndrome in a case of myxedema coma.

PubMed

Yanamandra, Uday; Kotwal, Narendra; Menon, Anil; Nair, Velu

2012-05-01

Ogilvie's syndrome [acute colonic pseudo-obstruction (ACPO)] presents as massive colonic dilatation without a mechanical cause, usually in critically ill patients due to imbalanced sympathetic and parasympathetic activity. The initial therapy remains conservative with supportive measures (correction of metabolic, infectious or pharmacologic factors) followed by neostigmine and decompressive colonoscopy. Surgery is reserved for patients with clinical deterioration or with evidence of colonic ischemia or perforation. A 60-year-old lady presented with fever, altered sensorium, obstipation, bradycardia and abdominal distension. Investigation revealed hyponatremia and acute colonic pseudo-obstruction. Supportive measures and decompressive colonoscopy were not of great benefit. Thyroid profile was suggestive of primary hypothyroidism. Colonic motility was restored only on starting thyroxin. The case is illustrative of the need to consider hypothyroidism, a common endocrine disorder, in the differential diagnosis of Ogilvie's.

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause

PubMed Central

Sullivan, Shannon D.; Sarrel, Philip M.; Nelson, Lawrence M.

2016-01-01

Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychological impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective hormone replacement therapy options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ~50 years. We address special populations of women with POI, including women with Turner Syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women. PMID:27912889

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

[State of the art in fluid and volume therapy : A user-friendly staged concept].

PubMed

Rehm, M; Hulde, N; Kammerer, T; Meidert, A S; Hofmann-Kiefer, K

2017-03-01

Adequate fluid therapy is highly important for the perioperative outcome of our patients. Both, hypovolemia and hypervolemia can lead to an increase in perioperative complications and can impair the outcome. Therefore, perioperative infusion therapy should be target-oriented. The main target is to maintain the patient's preoperative normovolemia by using a sophisticated, rational infusion strategy.Perioperative fluid losses should be discriminated from volume losses (surgical blood loss or interstitial volume losses containing protein). Fluid losses as urine or perspiratio insensibilis (0.5-1.0 ml/kg/h) should be replaced by balanced crystalloids in a ratio of 1:1. Volume therapy step 1: Blood loss up to a maximum value of 20% of the patient's blood volume should be replaced by balanced crystalloids in a ratio of 4(-5):1. Volume therapy step 2: Higher blood losses should be treated by using iso-oncotic, preferential balanced colloids in a ratio of 1:1. For this purpose hydroxyethyl starch can also be used perioperatively if there is no respective contraindication, such as sepsis, burn injuries, critically ill patients, renal impairment or renal replacement therapy, and severe coagulopathy. Volume therapy step 3: If there is an indication for red cell concentrates or coagulation factors, a differentiated application of blood and blood products should be performed.

Phytoestrogens: a viable option?

PubMed

Russell, Lori; Hicks, G Swink; Low, Annette K; Shepherd, Jinna M; Brown, C Andrew

2002-10-01

Estrogen replacement therapy is one of the most commonly prescribed medicines in the United States by traditional medical professionals. Over the past decade, the market for complementary/ alternative therapies for hormone replacement has dramatically increased. Women are seeking more "natural" alternatives to treat menopausal symptoms. Well-designed randomized clinical trials are often lacking, as is the information on efficacy and safety. This article will review several popular herbal therapies for menopausal symptoms including phytoestrogens, black cohosh (Cimicifuga racemosa), dong quai (Angelica sinensis), chast tree (Vitex agnus-castus), and wild Mexican yam. Their use, mechanism of action, and adverse effects are outlined.

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update.

PubMed

Petak, Steven M; Nankin, Howard R; Spark, Richard F; Swerdloff, Ronald S; Rodriguez-Rigau, Luis J

2002-01-01

In these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) men with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from testosterone replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, inpatients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography,testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections, patches, or topically applied gel in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation option scan be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm.

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

PubMed

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

Evaluation of the effects of colostrum replacer supplementation of the milk replacer ration on the occurrence of disease, antibiotic therapy, and performance of pre-weaned dairy calves.

PubMed

Chamorro, Manuel F; Cernicchiaro, Natalia; Haines, Deborah M

2017-02-01

The objective of this study was to evaluate the effects of colostrum supplementation of the milk replacer ration on disease occurrence, antibiotic therapy, and performance of pre-weaned dairy calves with adequate transfer of passive immunity. Two hundred and two 1-d-old Holstein dairy calves were assigned to 1 of 2 groups after arrival to a dairy calf rearing facility. Calves assigned to the control group (n = 100) received milk replacer (28% crude protein and 20% crude fat) without colostrum inclusion twice daily. Calves assigned to the treatment group (n = 102) received 150 g of supplemental colostrum replacer powder added to their milk replacer twice daily for the first 14 d of life. Before group assignment, serum samples were collected from all calves to confirm transfer of passive immunity. Calves were evaluated daily until weaning (56 d of life) for signs of clinical disease as well as any treatment with antibiotics. Presentation of clinical disease and antibiotic treatment was recorded daily by personnel blinded to treatment allocation. Adequate transfer of passive immunity was confirmed in all calves at the start of the study and mean serum IgG values were similar among calves from treatment and control groups. The odds ratios of having abnormal feces and abnormal respiration during the pre-weaning period for calves from the treatment group were 0.15 and 0.46 the odds ratios of calves from the control group, respectively. The odds ratios of receiving antibiotic therapy during the pre-weaning period for calves from the treatment group were 0.09 the odds ratios of calves from the control group. Mean body weight and average daily gain at weaning were not significantly different among calves from the treatment and control groups. Colostrum replacer supplementation of the milk replacer ration was effective in reducing antibiotic therapy and occurrence of disease during the pre-weaning period. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

PubMed

Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

2016-09-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Antigen-specific therapy of Graves´ disease and orbitopathy by induction of tolerance.

PubMed

Ungerer, Martin; Fabbender, Julia; Holthoff, Hans-Peter

2018-06-01

Graves´ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice. T cell epitope-derived linear peptides have been identified using immunized HLA-DR3 transgenic mice, which may induce tolerance towards TSHR. A combination of such peptides are being investigated in a first clinical phase I trial in patients with Graves´ disease. Alternatively, intravenous administration of cyclic peptides derived from the interaction site of the TSHR A domain with stimulatory anti-TSHR antibodies can re-establish tolerance towards the antigen in immunized mice, improving symptoms of Graves´ disease within 3 - 4 months after starting these therapies. In immunologically naïve mice, administration of the cyclic peptides did not induce any immune response.

Amphibians and ultra high diluted thyroxine--further experiments and re-analysis of data.

PubMed

Endler, Peter Christian; Scherer-Pongratz, Waltraud; Harrer, Bernhard; Lingg, Gerhard; Lothaller, Harald

2015-10-01

A model of thyroxine and metamorphosis of highland amphibians is frequently mentioned as an example of experiments on extremely diluted substances in discussions around 'homeopathy'. The model was scrutinized by reanalysing the results of the initial researcher A and a second researcher B as well as of 5 external researchers C between 1990 and 2013. Rana temporaria larvae were taken from an alpine highland biotope. The test solution was thyroxine 10(-30) (T30x), tetra-iodo-thyronine sodium pentahydrate diluted with pure water in 26 steps of 1:10, being agitated after each step. Analogously prepared water (W30x) was used for control. Tadpoles were observed from the 2-legged to the 4-legged stage. Experiments were performed in different years, at different times of season, and their duration could vary. Frequencies of 4-legged animals, effect sizes and areas under the curves (AUCs) were calculated and regression analyses were performed to investigate possible correlations between year, season, duration etc. Experiments were in line with animal protection guidelines. The total set of data A + B + C as well as subsets A (initial researcher, N=286+293), B (second centre, 965 + 965) and C (5 external researchers, 690 + 690) showed an effect of extremely diluted agitated thyroxine reverse to that known of molecular thyroxin, i.e. test values were below control by 11.4% for A, 9.5% for B and 7.0% for C (p<0.001 for each of the subsets). The effect size (Cohen's d) was >0.8 (large) for both A and B and 0.74 (medium) for C. Although a perfect reproducibility was not obtained, this paradoxical phenomenon was generally consistent in different observations. Correlations were found between details of laboratory handling, as well as environment temperature, and the size of the results. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

PubMed Central

Tillotson, S. L.; Fuggle, P. W.; Smith, I.; Ades, A. E.; Grant, D. B.

1994-01-01

OBJECTIVES--To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN--A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING--First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS--361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES--Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS--There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS--Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education. PMID:7920127

Iodine-131 therapy alters the immune/inflammatory responses in the thyroids of patients with Graves' disease.

PubMed

Du, Wenhua; Dong, Qingyu; Lu, Xiaoting; Liu, Xiaomeng; Wang, Yueli; Li, Wenxia; Pan, Zhenyu; Gong, Qian; Liang, Cuige; Gao, Guanqi

2017-03-01

The aim of the present study was to evaluate the serum levels of interleukin-6 (IL-6), CXC chemokine ligand-10 (CXCL-10) and intercellular adhesion molecule-l (ICAM-1) in patients with Graves' disease (GD) following iodine-131 ( 131 I) therapy. A total of 30 patients with GD participated in the present study. Serum cytokine levels were measured with ELISA, and correlation analyses were performed. Serum levels of IL-6, CXCL-10 and ICAM-1 were significantly higher in patients with GD prior to treatment than those in the control subjects (P<0.01). Following 131 I therapy, the serum levels of IL-6 and CXCL-10 in patients with GD were markedly increased within the first week, gradually decreased to the pretreatment level in the subsequent six months and decreased further at 18 months post-treatment. However, the serum levels of IL-6 and CXCL-10 in patients with GD at 18 months following 131 I therapy remained significantly higher than in control subjects (P<0.01). Conversely, serum ICAM-1 levels in patients with GD were gradually increased in the 12 months following 131 I therapy and reached a relatively stable level thereafter. Furthermore, the Pearson's correlation analysis indicated that the serum levels of IL-6, CXCL-10 and ICAM-1 were not associated with free triiodothyronine, the free thyroxine index, and thyroid-stimulating hormone in these patients. 131 I therapy was able to alter the immune/inflammatory responses in the thyroids of patients with GD. However, these cytokines (IL-6, CXCL-10, and ICAM-1) are not associated with thyroid function; therefore, they cannot be used as prognostic markers for the 131 I therapy of GD.

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: hypothyroidism.

PubMed

Persani, Luca; Bonomi, Marco

2014-01-01

In patients with primary hypothyroidism (PH), L-T4 replacement therapy can safely be adjusted to the individual needs by testing serum thyrotropin (TSH) concentration exclusively. Central hypothyrodism (CeH) is a particular hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. CeH is about 1000-fold rarer than PH and raises several challenges for clinicians, mainly because they cannot rely on the systematic use of the reflex TSH strategy for diagnosis or therapy monitoring. Therefore, L-T4 replacement in CeH should rely on the combined evaluation of several biochemical and clinical parameters in order to overcome the lack of accuracy of the single index. The management of CeH replacement is further complicated by the frequent combination with other pituitary deficiencies and their treatment. © 2014 Elsevier B.V. All rights reserved.

A case of rhabdomyolysis after kidney transplantation successfully managed with intensive continuous dialysis.

PubMed

Shahbazov, Rauf; Fox, Michael; Alejo, Jennifer L; Anjum, Malik A; Azari, Feredun; Doyle, Alden; Agarwal, Avinash; Brayman, Kenneth L

2018-04-01

Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.

Lithium overdose and delayed severe neurotoxicity: timing for renal replacement therapy and restarting of lithium.

PubMed

de Cates, Angharad N; Morlet, Julien; Antoun Reyad, Ayman; Tadros, George

2017-10-25

This is a case report of a man in his 60s who presented to an English hospital following a significant lithium overdose. He was monitored for 24 hours, and then renal replacement therapy was initiated after assessment by the renal team. As soon as the lithium level returned to normal therapeutic levels (from 4.7 mEq/L to 0.67 mEq/L), lithium was restarted by the medical team. At this point, the patient developed new slurred speech and later catatonia. In this case report, we discuss the factors that could determine which patients are at risk of neurotoxicity following lithium overdose and the appropriate decision regarding when and how to consider initiation of renal replacement therapy and restarting of lithium. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

PubMed

Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

2004-09-01

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

Influence of L-thyroxine administration on poor-platelet plasma VEGF concentrations in patients with induced short-term hypothyroidism, monitored for thyroid carcinoma.

PubMed

Dedecjus, Marek; Kołomecki, Krzysztof; Brzeziński, Jan; Adamczewski, Zbigniew; Tazbir, Józef; Lewiński, Andrzej

2007-02-01

Angiogenesis is a process of new blood vessel development from pre-existing vasculature. It is a crucial process in normal physiology, as well as in several pathological conditions. The vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens, involved in normal angiogenesis and in tumour development. The aim of the present study was to estimate the influence of L-thyroxine (L-T4) administration on poor-platelet plasma (P-PP) VEGF concentrations in patients with induced short-term hypothyroidism, monitored for differentiated thyroid carcinoma. In the present study, P-PP concentrations of VEGF, thyroglobulin, thyrotropin and free thyroid hormones were investigated in a population of 24 hypothyroid patients, who were withdrawn from L-T4 treatment for 5 weeks and studied before and after 2 months of L-T4 therapy. Only healthy female patients with no evidence of metastasis in whole body scintigraphy were included in the study. They were then compared with 20 healthy control subjects, matched for age, sex and body mass index (BMI). The patients had significantly lower plasma VEGF concentrations before treatment with L-T4 than after administration of that hormone. There was no significant difference in plasma VEGF levels, either between the patients treated with L-T4, and the controls, or between the patients untreated with L-T4, and the controls. Even short-time changes in thyrometabolic profile exert an important influence on P-PP VEGF concentrations, even if there is no thyroid tissue.

Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons

PubMed Central

Cave, John W.; Wang, Meng; Baker, Harriet

2014-01-01

Clinical trials engrafting human fetal ventral mesencephalic tissue have demonstrated, in principle, that cell replacement therapy provides substantial long-lasting improvement of motor impairments generated by Parkinson's Disease (PD). The use of fetal tissue is not practical for widespread clinical implementation of this therapy, but stem cells are a promising alternative source for obtaining replacement cells. The ideal stem cell source has yet to be established and, in this review, we discuss the potential of neural stem cells in the adult subventricular zone (SVZ) as an autologous source of replacement cells. We identify three key challenges for further developing this potential source of replacement cells: (1) improving survival of transplanted cells, (2) suppressing glial progenitor proliferation and survival, and (3) developing methods to efficiently produce dopaminergic neurons. Subventricular neural stem cells naturally produce a dopaminergic interneuron phenotype that has an apparent lack of vulnerability to PD-mediated degeneration. We also discuss whether olfactory bulb dopaminergic neurons derived from adult SVZ neural stem cells are a suitable source for cell replacement strategies. PMID:24574954

Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continuous renal replacement therapy with calcium-free replacement solution.

PubMed

See, Kay Choong; Lee, Margaret; Mukhopadhyay, Amartya

2009-01-01

Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group), received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was used, more citrate was required (mean 280 ml/h, CI 227.2-332.8 vs. 265 ml/h, CI 203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6 ml/h, CI 26.8-76.4, P < or = 0.0001).

Regulation of Ca(2+)-dependent protein turnover in skeletal muscle by thyroxine

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Bernstein, Paul L.; Ludemann, Robert; Etlinger, Joseph D.

1986-01-01

Dantrolene, an agent that inhibits Ca(2+) mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca(2+)-dependent nonlysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

PubMed

Krysiak, R; Szkrobka, W; Okopien, B

2015-04-01

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

Nicotine replacement therapy, professional therapy, snuff use and tobacco smoking: a study of smoking cessation strategies in southern Sweden.

PubMed

Lindström, Martin

2007-12-01

The strategies used to support smoking cessation among quitters were investigated according to year of smoking cessation and sociodemographic characteristics. The 2004 public health survey in Skåne, Sweden, is a cross-sectional study. A total of 27,757 people aged 18-80 answered a postal questionnaire. The participation rate was 59%. Different strategies to support smoking cessation--that is, no therapy, nicotine replacement (NRT), professional therapy and snus (snuff) use, were investigated among quitters according to year of smoking cessation, and demographic and socioeconomic characteristics. 14.9% of the men and 18.1% of the women were daily smokers. The prevalence of daily snus use was 19.5% among men but only 2.3% among women. Stratifying the data according to year of smoking cessation (1938-2004) revealed a significant increase in active smoking cessation strategies such as NRT, professional therapy and snus use. NRT was more common among women (23.6%) than men (14.8%) among smokers who quit in 2000-4, but snus use was more common among men (30.4% versus 8.7%). No replacement or other therapy at all was significantly more common among women (63.6%) than men (52.1%). People aged 35-80 years used more nicotine replacement than people aged 18-34, while men aged 18-34 used snus to quit smoking significantly more than men aged 55-80. Snus is used commonly among men as a support for smoking cessation in Sweden. Women use pharmacological NRT to a greater extent, but this can probably not compensate for the much higher extent of snuff use as a cessation strategy among men.

Nicotine replacement therapy, professional therapy, snuff use and tobacco smoking: a study of smoking cessation strategies in southern Sweden

PubMed Central

Lindström, Martin

2007-01-01

Objectives The strategies used to support smoking cessation among quitters were investigated according to year of smoking cessation and sociodemographic characteristics. Methods The 2004 public health survey in Skåne, Sweden, is a cross‐sectional study. A total of 27 757 people aged 18–80 answered a postal questionnaire. The participation rate was 59%. Different strategies to support smoking cessation—that is, no therapy, nicotine replacement (NRT), professional therapy and snus (snuff) use, were investigated among quitters according to year of smoking cessation, and demographic and socioeconomic characteristics. Results 14.9% of the men and 18.1% of the women were daily smokers. The prevalence of daily snus use was 19.5% among men but only 2.3% among women. Stratifying the data according to year of smoking cessation (1938–2004) revealed a significant increase in active smoking cessation strategies such as NRT, professional therapy and snus use. NRT was more common among women (23.6%) than men (14.8%) among smokers who quit in 2000–4, but snus use was more common among men (30.4% versus 8.7%). No replacement or other therapy at all was significantly more common among women (63.6%) than men (52.1%). People aged 35–80 years used more nicotine replacement than people aged 18–34, while men aged 18–34 used snus to quit smoking significantly more than men aged 55–80. Conclusions Snus is used commonly among men as a support for smoking cessation in Sweden. Women use pharmacological NRT to a greater extent, but this can probably not compensate for the much higher extent of snuff use as a cessation strategy among men. PMID:18048619

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

PubMed

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

Thyroid hormones increase stomach goblet cell numbers and mucin expression during indomethacin induced ulcer healing in Wistar rats.

PubMed

Namulema, Jackline; Nansunga, Miriam; Kato, Charles Drago; Kalange, Muhammudu; Olaleye, Samuel Babafemi

2018-01-01

Gastric ulcers are mucosal discontinuities that may extend into the mucosa, submucosa or even deeper. They result from an imbalance between mucosal aggressors and protective mechanisms that include the mucus bicarbonate layer. Thyroid hormones have been shown to accelerate gastric ulcer healing in part by increasing the adherent mucus levels. However, the effects of thyroid hormones on goblet cell numbers and expression of neutral and acidic mucins during ulcer healing have not been investigated. Thirty six adult male Wistar rats were randomly divided into six groups each with six animals. Group 1 (normal control) and group 2 (negative control) were given normal saline for eight weeks. Groups 3 and 4 were given 100 μg/kg per day per os of thyroxine so as to induce hyperthyroidism. Groups 5 and 6 received 0.01% ( w / v ) Propylthiouracil (PTU) for 8 weeks so as to induce hypothyroidism. After thyroid hormonal levels were confirmed using radioimmunoassay and immunoradiometric assays, ulcer induction was done using 40 mg/kg intragastric single dose of Indomethacin in groups 2, 3 and 5. Stomachs were extracted after day 3 and 7 of ulcer induction for histological examination. Histochemistry was carried out using Periodic Acid Shiff and Alcian Blue. The number of acidic and neutral goblet cells were determined by counting numbers per field. Mucin expression (%) was determined using Quick Photo Industrial software version 3.1. The numbers of neutral goblet cells (cells/field) increased significantly ( P  < 0.05) in the ulcer+thyroxine (14.67 ± 0.33), thyroxine (17.04 ± 1.71) and ulcer+PTU (12.89 ± 1.06) groups compared to the normal control (10.78 ± 1.07) at day 3. For the acidic goblet cells, differences between treatment groups were more pronounced at day 7 between the ulcer+thyroxine (22.56 ± 1.26) and thyroxine (22.89 ± 0.80). We further showed that percentage expression of both neutral and acidic mucins was significantly higher in the ulcer+thyroxine (9.23 ± 0.17 and 6.57 ± 0.35 respectively) and thyroxine groups (9.66 ± 0.21 and 6.33 ± 0.38 respectively) as compared to the normal control group (4.08 ± 0.20 and 4.38 ± 0.11 respectively) at day 3 after ulcer induction. This study confirms the role played by thyroid hormones in healing of indomethacin induced gastric ulcers. The study further demonstrates increased numbers of both neutral and acidic goblet cells and the increase in expression of both neutral and acidic mucins during healing of indomethacin induced ulcers.

[Particular evolution of the thyroid state in Grave's disease: two cases].

PubMed

Cherif, Lotfi; Ben Abdallah, Néjib; Khairi, Karima; Hadj Ali, Inçaf; Turki, Sami; Ben Maïz, Hédi

2003-09-01

We report two cases of Grave's disease (GD) caracterized by the succession of hypothyroid and hyperthyroid states. Case 1: A 32 years old woman, has presented initially a typical GD with hyperthyroidism. Grave's ophtalmopathy and homogenous goiter. Four months later, she presented a spontaneous hypothyroidism necessiting treatment with thyroxine and a severe myasthenia gravis. More later (6 months), she experienced symptoms of hyperthyroidism after thymectomy. The level of anti-thyrotropin-receptor antibodies (TSab) was very high (141 UI/I, NV < 10). Case 2: A 29 years old woman has been treated by thyroxine (150 microg/day) for a primary hypothyroidism. Ten months later, she presented symptoms of hyperthyroidism even after stoppage of thyroxine. TSH value was decreased (TSH < 0.05 microU/ml) and FT4 level was raised (FT4 = 25.5 pmol/l). The thyroid antibodies were positive. We discuss, after review of the litterature, the physiopathological mecanisms of these changes in the thyroid state, particularly the role of the blocking and stimulating anti-thyrotropin-receptor antibodies.

New medications which decrease levothyroxine absorption.

PubMed

John-Kalarickal, Jennifer; Pearlman, Gwen; Carlson, Harold E

2007-08-01

Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.

THE EFFECT OF X RAYS ON THE LARVA OF THE ANFIBI ANURI. GRAFTS OF JOINTS AND ADMINISTRATION OF THYROXINE (in Italian)

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

Perri, T.

1959-11-01

The effect of x rays on the larvae of Anfibi anuri and particularly on their endocrine balunce was studied. The effect studied was the variation of the growth velocity of the joints of normal larvae transplanted onto x-irradiated larvae, either homoplastically (Bufo vulgaris and Bufo viridis) or heteroplastically (Bufo viridis and Bufo vulgaris). A joint transplant from normal larvae of Bufo vulgaris or Bufo viridis on x-irradiated larvae of Bufo vulgaris has a growth rate much less than that found in transplants on normal larvae of Bufo vulgaris. It is suggested that this results from the radiation- induced decrease ofmore » the endocrine activity of the carrier, particularly of the thyroxine activity. It is seen that in transplants from Bufo viridis on irradiated Bufo vulgaris, if the carrier larvae are treated with thyroxine, the transplants have a sharply increased growth. (J.S.R)« less

The relationship between thyroxine, oestradiol, and postnatal alopecia, with relevance to women's health in general.

PubMed

Pringle, T

2000-11-01

Post-partum hair loss is possibly due to a reduction in the levels of oestradiol and thyroxine postnatally. Alopecia and/or a persistent loss of hair condition postnatally is associated with a group of symptoms (a syndrome), wherein postnatal depression is significant, as a result of physiologically inadequate levels of thyroxine (T4) and oestradiol (E2), secondary to physiological postnatal anterior pituitary dysfunction. Using this hypothesis, the author began to apply the same hypothesis to other female patients, who were not postpartum, but with similar symptomatology. The author became aware of the necessity for an adequate level of T4 to be present for correct oestrogenization to occur. He then goes on to hypothesize on the synergistic relationship that T4 and oestradiol may have in premenstrual syndrome (PMS), infertility, dysfunctional uterine bleeding, poor placental function, osteoporosis, and anorexia nervosa. He also discusses the role lowering T4 could play in the treatment of terminal cancer breast in premenopausal women.

Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

PubMed

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2011-05-19

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

The Fabrazyme shortage--a call to action for metabolic physicians.

PubMed

Sirrs, Sandra

2011-01-01

The recent shortages of enzyme replacement therapy for Fabry disease have highlighted areas of vulnerability for patients who require this treatment. Guidelines on allocation of limited stock of enzyme replacement therapy are of use for clinicians dealing with the current shortages. However, the community of metabolic physicians must advocate for changes that will minimize the impact of future drug shortages for their patients with lysosomal storage diseases. Copyright © 2010 Elsevier Inc. All rights reserved.

Combination nicotine replacement therapy: strategies for initiation and tapering.

PubMed

Hsia, Stephanie L; Myers, Mark G; Chen, Timothy C

2017-04-01

Several studies and meta-analyses have demonstrated the efficacy of combination nicotine replacement therapy (NRT) for patients who wish to quit smoking. However, there is limited guidance with respect to initiation and tapering of combination NRT. We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies. Copyright © 2017. Published by Elsevier Inc.

[Cost-effectiveness analysis of renal replacement therapies: how should we design research on these interventions in Brazil?].

PubMed

Sancho, Leyla Gomes; Dain, Sulamis

2008-06-01

This study aims to contribute to the discussion on the possibility of applying health economics assessment, specifically the cost-effectiveness technique, to renal replacement therapies for end-stage renal failure. A review was conducted on the interventions and their alternative courses from the perspective of the various methodological proposals in the literature, considering the availability of data and information in Brazil to back this type of research.

Does postmenopausal hormone replacement therapy affect intraocular pressure?

PubMed

Abramov, Yoram; Borik, Sharon; Yahalom, Claudia; Fatum, Muhammad; Avgil, Gadiel; Brzezinski, Amnon; Banin, Eyal

2005-08-01

To assess the effects of postmenopausal hormone replacement therapy (HRT) on intraocular pressure (IOP). This was a cross-sectional controlled study, including 107 women aged 60 to 80 years receiving HRT and 107 controls who have never received HRT. All subjects underwent IOP assessment and funduscopic photography for cup-to-disc (C/D) ratios, and completed questionnaires regarding personal and family history of glaucoma, hormone replacement therapy, lifetime estrogen and progesterone exposure, and cardiovascular risk factors. Main Outcome Measures included IOP, prevalence of increased IOP, and C/D ratios. The groups did not differ in mean IOP (15.3 versus 15.3 mm Hg), mean vertical (0.18 versus 0.21) and horizontal (0.17 versus 0.14) C/D ratios, and in prevalence of increased IOP (15% versus 14%), C/D ratio (7% versus 7%), or glaucoma (9% versus 11%). A personal history of ischemic heart disease was the only risk factor associated with increased IOP (O.R. = 4.63, P = 0.003). Lifetime estrogen and progesterone exposure, including pregnancies, deliveries, menstruation years, and the use of oral contraceptives did not significantly affect the risk for increased IOP. Hormone replacement therapy and lifetime estrogen and progesterone exposure do not seem to affect IOP or the risk for increased IOP. A personal history of ischemic heart disease may be associated with a higher risk for this disorder.

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

PubMed

Chauveau, Philippe; Couzi, Lionel; Vendrely, Benoit; de Précigout, Valérie; Combe, Christian; Fouque, Denis; Aparicio, Michel

2009-10-01

The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects.

PubMed

Mazziotti, G; Formenti, A M; Frara, S; Roca, E; Mortini, P; Berruti, A; Giustina, A

2017-11-01

The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI. © 2017 European Society of Endocrinology.

Nursing issues in renal replacement therapy: organization, manpower assessment, competency evaluation and quality improvement processes.

PubMed

Graham, Patricia; Lischer, Eileen

2011-01-01

For the patient with acute kidney injury, continuous renal replacement therapy (CRRT) is a treatment option that has application for the hemodynamically unstable critically ill patient. The decision to initiate a continuous renal replacement modality depends not only on the physician, either the nephrologist or intensivist, but also on the availability of specially trained nursing resources. This article will explore the nursing collaborative model of care at a large university-based research and teaching Medical Center in Southern California. The focus will be on nursing issues in CRRT including organization of educational programs, manpower assessment, competency evaluation, and quality improvement processes. © 2011 Wiley Periodicals, Inc.

Preventing Mitochondrial Diseases: Embryo-Sparing Donor-Independent Options.

PubMed

Adashi, Eli Y; Cohen, I Glenn

2018-05-01

Mutant mitochondrial DNA gives rise to a broad range of incurable inborn maladies. Prevention may now be possible by replacing the mutation-carrying mitochondria of zygotes or oocytes at risk with donated unaffected counterparts. However, mitochondrial replacement therapy is being held back by theological, ethical, and safety concerns over the loss of human zygotes and the involvement of a donor. These concerns make it plain that the identification, validation, and regulatory adjudication of novel embryo-sparing donor-independent technologies remains a pressing imperative. This Opinion highlights three emerging embryo-sparing donor-independent options that stand to markedly allay theological, ethical, and safety concerns raised by mitochondrial replacement therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

PubMed Central

Tendler, Rabbi Moshe D.; Loike, John D.

2015-01-01

The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal. PMID:26241230

Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice.

PubMed

Kesterke, Matthew J; Judd, Margaret A; Mooney, Mark P; Siegel, Michael I; Elsalanty, Mohammed; Howie, R Nicole; Weinberg, Seth M; Cray, James J

2018-07-01

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development. © 2018 Anatomical Society.

Bile salt kinetics in cystic fibrosis: influence of pancreatic enzyme replacement

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

Watkins, J.B.; Tercyak, A.M.; Szczepanik, P.

1977-01-01

Bile acid kinetics was investigated by stable isotope dilution technique in 6 children (ages 3/sup 1///sub 2/ months to 4/sup 1///sub 2/ years) with previously untreated cystic fibrosis. All of the patients had clinical and laboratory evidence of malabsorption, normal intestinal mucosal function, as judged by glucose absorption, intestinal histology, disaccharidase levels, and normally functioning gallbladders. The children were maintained on a constant diet throughout the study period; fat intake averaged 4.2 g per kg per day. Before administration of pancreatic enzyme replacement, fat excretion equalled 50 +- 4% (mean +- SE) of intake and was reduced to 20 +-more » 1.0% of intake after therapy. Total bile acid pool size nearly doubled during enzyme replacement from 379 +- 32 ..mu..moles per kg to 620 +- 36 ..mu..moles per kg with secondary bile acids comprising 57% of the total pool before therapy and 40% after therapy. The data indicate that both primary and secondary bile acids are conserved within the enterohepatic circulation during enzyme therapy, and that the mechanism for the regulation of hepatic bile acid synthesis is intact in cystic fibrosis. However, the demonstration that large amounts of bile acid continue to be excreted during therapy suggests that interruption of the enterohepatic circulation continues and that deficiencies of the intraluminal phase may persist during enzyme therapy in this disease.« less

Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

PubMed

Symer, Matthew M; Wong, Natalie Z; Abelson, Jonathan S; Milsom, Jeffrey W; Yeo, Heather L

2018-06-01

Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer. We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects' use of hormone replacement therapy at the time of randomization: never, current, or former users. A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and < 10% had not completed high school. The never-user group was slightly older than the current or former user groups (average, 63.8 vs. 61.4 vs. 63.3 years; P < .001). Almost one-half (47.1%) of the current users had undergone hysterectomy, compared with 21.6% of never-users and 34.0% of former users (P < .001). Adjusted colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P < .001). Hormone replacement therapy is associated with a reduced risk of colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Predictors of survival and ability to wean from short-term mechanical circulatory support device following acute myocardial infarction complicated by cardiogenic shock.

PubMed

Garan, A Reshad; Eckhardt, Christina; Takeda, Koji; Topkara, Veli K; Clerkin, Kevin; Fried, Justin; Masoumi, Amirali; Demmer, Ryan T; Trinh, Pauline; Yuzefpolskaya, Melana; Naka, Yoshifumi; Burkhoff, Dan; Kirtane, Ajay; Colombo, Paolo C; Takayama, Hiroo

2017-11-01

Cardiogenic shock following acute myocardial infarction (AMI-CS) portends a poor prognosis. Short-term mechanical circulatory support devices (MCSDs) provide hemodynamic support for patients with cardiogenic shock but predictors of survival and the ability to wean from short-term MCSDs remain largely unknown. All patients > 18 years old treated at our institution with extra-corporeal membrane oxygenation or short-term surgical ventricular assist device for AMI-CS were studied. We collected acute myocardial infarction details with demographic and hemodynamic variables. Primary outcomes were survival to discharge and recovery from MCSD (i.e. survival without heart replacement therapy including durable ventricular assist device or heart transplant). One hundred and twenty-four patients received extra-corporeal membrane oxygenation or short-term surgical ventricular assist device following acute myocardial infarction from 2007 to 2016; 89 received extra-corporeal membrane oxygenation and 35 short-term ventricular assist device. Fifty-five (44.4%) died in the hospital and 69 (55.6%) survived to discharge. Twenty-six (37.7%) required heart replacement therapy (four transplant, 22 durable ventricular assist device) and 43 (62.3%) were discharged without heart replacement therapy. Age and cardiac index at MCSD implantation were predictors of survival to discharge; patients over 60 years with cardiac index <1.5 l/min per m 2 had a low likelihood of survival. The angiographic result after revascularization predicted recovery from MCSD (odds ratio 9.00, 95% confidence interval 2.45-32.99, p=0.001), but 50% of those optimally revascularized still required heart replacement therapy. Cardiac index predicted recovery from MCSD among this group (odds ratio 4.06, 95% confidence interval 1.45-11.55, p=0.009). Among AMI-CS patients requiring short-term MCSDs, age and cardiac index predict survival to discharge. Angiographic result and cardiac index predict ventricular recovery but 50% of those optimally revascularized still required heart replacement therapy.

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study.

PubMed

Estai, Mohamed Abdalla; Suhaimi, Farihah Haji; Das, Srijit; Fadzilah, Fazalina Mohd; Alhabshi, Sharifah Majedah Idrus; Shuid, Ahmad Nazrun; Soelaiman, Ima-Nirwana

2011-01-01

Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.

Associations of race and ethnicity with anemia management among patients initiating renal replacement therapy.

PubMed Central

Weisbord, Steven D.; Fried, Linda F.; Mor, Maria K.; Resnick, Abby L.; Kimmel, Paul L.; Palevsky, Paul M.; Fine, Michael J.

2007-01-01

BACKGROUND: Many patients initiate renal replacement therapy with suboptimal anemia management. The factors contributing to this remain largely unknown. The aim of this study was to assess the associations of race and ethnicity with anemia care prior to the initiation of renal replacement therapy. METHODS: Using data from the medical evidence form filed for patients who initiated renal replacement therapy between 1995-2003, we assessed racial and ethnic differences in pre-end-stage renal disease hematocrit levels, the use of erythropoiesis stimulation agents (ESAs), the proportion of patients with hematocrit levels > or = 33% and the proportion of patients with hematocrit levels < 33% that did not receive ESA. We also examined secular trends in racial and ethnic differences in these parameters. RESULTS: In multivariable analyses, non-Hispanic blacks had lower hematocrit levels (delta hematocrit = -0.97%, 95% CI: -1.00-0.94%), and were less likely to receive ESA (OR = 0.82, 95% CI: 0.81-0.84), to initiate renal replacement therapy with hematocrit > or = 33% (OR = 0.78, 95% CI: 0.77-0.79) or to receive ESA if the hematocrit was < 33% (OR = 0.79, 95% CI: 0.77-0.80) than non-Hispanic whites. White Hispanics also had lower hematocrit levels (delta hematocrit = -0.42%, 95% CI:-0.47% to -0.37%), and were less likely to receive ESA (OR = 0.86, 95% CI: 0.85-0.88), to have hematocrit levels > or = 33% (OR = 0.91, 95% CI: 0.89-0.93) or to receive ESA if the hematocrit was < 33% (OR = 0.85, 95% CI: 0.83-0.87) than non-Hispanic whites. These disparities persisted over the eight-year study period. CONCLUSIONS: African-American race and Hispanic ethnicity are associated with suboptimal pre-end-stage renal disease anemia management. Efforts to improve anemia care should incorporate targeted interventions to decrease these disparities. PMID:18020096

Late pubertal growth spurt in a girl with growth hormone deficiency: Is Kaufmann therapy effective in a girl with short stature who responds poorly to growth hormone therapy and estrogen-replacement therapy?

PubMed

Yasuda, Katsuhiko

2017-05-01

A Japanese senior high school girl aged 18 years and 5 months with growth hormone deficiency was referred for primary amenorrhea. Her height was 1.36 m, and her bodyweight was 23.5 kg. She had received daily growth hormone therapy from the age of 5 years. Growth hormone therapy was discontinued at the age of 16 years and 11 months, and estrogen-replacement therapy (ERT) was started to stimulate secondary sexual characteristics. Although ERT was performed until the age of 18 years and 11 months, genital bleeding did not occur. ERT was changed to Kaufmann therapy, and the first genital bleeding occurred 1 year and 4 months later. Finally, regular medically induced menses occurred at the age of 21 years and 10 months. Her height increased by 9 cm in 1 year after the initiation of menstrual bleeding. Kaufmann therapy was associated not only with menstrual bleeding but also with growth spurt. © 2017 Japan Society of Obstetrics and Gynecology.

No obvious sympathetic excitation after massive levothyroxine overdose: A case report.

PubMed

Xue, Jianxin; Zhang, Lei; Qin, Zhiqiang; Li, Ran; Wang, Yi; Zhu, Kai; Li, Xiao; Gao, Xian; Zhang, Jianzhong

2018-06-01

Thyrotoxicosis from an overdose of medicinal thyroid hormone is a condition that may be associated with a significant delay in onset of toxicity. However, limited literature is available regarding thyrotoxicosis attributed to excessive ingestion of exogenous thyroid hormone and most cases described were pediatric clinical researches. Herein, we presented the course of a patient who ingested a massive amount of levothyroxine with no obvious sympathetic excited symptoms exhibited and reviewed feasible treatment options for such overdoses. A 41-year-old woman patient with ureteral calculus ingested a massive amount of levothyroxine (120 tablets, equal to 6 mg in total) during her hospitalization. Her transient vital signs were unremarkable after ingestion except for significantly accelerated breathing rate of 45 times per minute. Initial laboratory findings revealed evidently elevated serum levels of thyroxine (T4) >320 nmol/L, free triiodothyronine (fT3) 10.44 pmol/L, and free thyroxine (fT4) >100 pmol/L. The patient had a history of hypothyroidism, which was managed with thyroid hormone replacement (levothyroxine 100 μg per day). Besides, she also suffered from systemic lupus erythematosus and chronic pancreatitis. This is a case of excessive ingestion of exogenous thyroid hormone in an adult. The interventions included use propranolol to prevent heart failure; utilize hemodialysis to remove redundant thyroid hormone from blood; closely monitor the vital signs, basal metabolic rate, blood biochemical indicators, and serum levels of thyroid hormone. The woman had no obvious symptoms of thyrotoxicosis. After 4 weeks, the results of thyroid function indicated that serum thyroid hormone levels were completely recovered to pre-ingestion levels. Accordingly, the levothyroxine was used again as before. Adults often exhibit more severe symptoms after intaking overdose levothyroxine due to their complex medical history and comorbidities than children. As for them, hemodialysis should be considered as soon as possible. Besides, diverse treatments according to specific symptoms and continuously monitoring were indispensable.

Bioengineered Lacrimal Gland Organ Regeneration in Vivo

PubMed Central

Hirayama, Masatoshi; Tsubota, Kazuo; Tsuji, Takashi

2015-01-01

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID:26264034

Biotechnological challenges of bioartificial kidney engineering.

PubMed

Jansen, J; Fedecostante, M; Wilmer, M J; van den Heuvel, L P; Hoenderop, J G; Masereeuw, R

2014-11-15

With the world-wide increase of patients with renal failure, the development of functional renal replacement therapies have gained significant interest and novel technologies are rapidly evolving. Currently used renal replacement therapies insufficiently remove accumulating waste products, resulting in the uremic syndrome. A more preferred treatment option is kidney transplantation, but the shortage of donor organs and the increasing number of patients waiting for a transplant warrant the development of novel technologies. The bioartificial kidney (BAK) is such promising biotechnological approach to replace essential renal functions together with the active secretion of waste products. The development of the BAK requires a multidisciplinary approach and evolves at the intersection of regenerative medicine and renal replacement therapy. Here we provide a concise review embracing a compact historical overview of bioartificial kidney development and highlighting the current state-of-the-art, including implementation of living-membranes and the relevance of extracellular matrices. We focus further on the choice of relevant renal epithelial cell lines versus the use of stem cells and co-cultures that need to be implemented in a suitable device. Moreover, the future of the BAK in regenerative nephrology is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Stem cell treatment of degenerative eye disease.

PubMed

Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A H; Leadbeater, Wendy; Scheven, Ben A

2015-05-01

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. Copyright © 2015. Published by Elsevier B.V.

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

PubMed

Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Hormone Replacement Therapy: MedlinePlus Health Topic

MedlinePlus

... Cancer Institute) Also in Spanish Menopause: Medicines to Help You (Food and Drug Administration) ... Hormone Therapy for the Primary Prevention of Chronic Conditions (U.S. Preventive Services Task Force) - ...

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement.

PubMed

Di Foggia, Valentina; Makwana, Priyanka; Ali, Robin R; Sowden, Jane C

2016-06-01

Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patient-specific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

PubMed Central

Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

2013-01-01

Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases

PubMed Central

Fujiwara, Masayuki; Kamikonya, Norihiko; Odawara, Soichi; Suzuki, Hitomi; Niwa, Yasue; Takada, Yasuhiro; Doi, Hiroshi; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-01-01

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers. PMID:25818629

Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions?

PubMed Central

Joffe, Barry I; Distiller, Larry A

2014-01-01

Clinicians should be cognizant of the close relationship that exists between two of the most common endocrine disorders, primary hypothyroidism and diabetes mellitus. This applies to patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM respectively). However, the association is greater in T1DM, probably because of the shared autoimmune predisposition. In patients with T2DM, the relationship is somewhat weaker and the explanation less clear-cut. Factors such as dietary iodine deficiency, metformin-induced thyroid stimulating hormone suppression and poor glycemic control may all be implicated. Further translational research is required for greater clarification. Biochemical screening for abnormal thyroid function in individuals who have diabetes is warranted, particularly in females with T1DM, and therapy with L-thyroxine appropriately instituted if hypothyroidism is confirmed. PMID:25512794

Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions?

PubMed

Joffe, Barry I; Distiller, Larry A

2014-12-15

Clinicians should be cognizant of the close relationship that exists between two of the most common endocrine disorders, primary hypothyroidism and diabetes mellitus. This applies to patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM respectively). However, the association is greater in T1DM, probably because of the shared autoimmune predisposition. In patients with T2DM, the relationship is somewhat weaker and the explanation less clear-cut. Factors such as dietary iodine deficiency, metformin-induced thyroid stimulating hormone suppression and poor glycemic control may all be implicated. Further translational research is required for greater clarification. Biochemical screening for abnormal thyroid function in individuals who have diabetes is warranted, particularly in females with T1DM, and therapy with L-thyroxine appropriately instituted if hypothyroidism is confirmed.

Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Study

PubMed Central

2010-01-01

Introduction Severe acute kidney injury (AKI) can be treated with either continuous renal replacement therapy (CRRT) or intermittent renal replacement therapy (IRRT). Limited evidence from existing studies does not support an outcome advantage of one modality versus the other, and most centers around the word use both modalities according to patient needs. However, cost estimates involve multiple factors that may not be generalizable to other sites, and, to date, only single-center cost studies have been performed. The aim of this study was to estimate the cost difference between CRRT and IRRT in the intensive care unit (ICU). Methods We performed a post hoc analysis of a prospective observational study among 53 centers from 23 countries, from September 2000 to December 2001. We estimated costs based on staffing, as well as dialysate and replacement fluid, anticoagulation and extracorporeal circuit. Results We found that the theoretic range of costs were from $3,629.80/day more with CRRT to $378.60/day more with IRRT. The median difference in cost between CRRT and IRRT was $289.60 (IQR 830.8-116.8) per day (greater with CRRT). Costs also varied greatly by region. Reducing replacement fluid volumes in CRRT to ≤ 25 ml/min (approximately 25 ml/kg/hr) would result in $67.20/day (23.2%) mean savings. Conclusions Cost considerations with RRT are important and vary substantially among centers. We identified the relative impact of four cost domains (nurse staffing, fluid, anticoagulation, and extracorporeal circuit) on overall cost differences, and hospitals can look to these areas to reduce costs associated with RRT. PMID:20346163

Hypothyroidism in an African forest buffalo (Syncerus caffer nanus).

PubMed

Allender, Matthew C; Briggs, Michael; Shipley, Clifford F

2007-03-01

An adult female African forest buffalo (Syncerus caffer nanus) of unknown age was presented with signs of recurrent hoof overgrowth, persistent anestrous, obesity, dull hair coat, and decreased activity level. Complete blood counts and serum biochemistry values were unremarkable. Decreased concentrations of total triiodothyronine and total thyroxine were noted compared with values for normal domestic cattle and a healthy African forest buffalo. Treatment with oral levothyroxine increased blood concentrations of total triiodothyronine and total thyroxine, and subsequent improvement in clinical signs included weight loss, hair regrowth, and reproductive cycling.

Extreme metabolic alkalosis with fludrocortisone therapy.

PubMed Central

Burns, A.; Brown, T. M.; Semple, P.

1983-01-01

We present an unusual case of extreme metabolic alkalosis resulting from severe hypokalaemia caused by unmonitored fludrocortisone therapy. Biochemical aspects of the disorder are discussed, as is the successful treatment with diuretics and potassium replacement. Some dangers of this therapy and necessary precautions are emphasized. PMID:6622340

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Chewing Tobacco: Not a Safe Alternative to Cigarettes

MedlinePlus

... chewed, sucked on or sniffed, rather than smoked. Nicotine is absorbed through the soft tissues of the mouth ... replacement therapy with nicotine gum or lozenges, a nicotine replacement that is also absorbed through the lining of the mouth, ...

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

PubMed

Somaraju, Usha Rani; Solis-Moya, Arturo

2016-11-23

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001). There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.

The breast cancer epidemic: 10 facts

PubMed Central

Schneider, A. Patrick; Zainer, Christine M.; Kubat, Christopher Kevin; Mullen, Nancy K.; Windisch, Amberly K.

2014-01-01

Breast cancer, affecting one in eight American women, is a modern epidemic. The increasing frequency of breast cancer is widely recognized. However, the wealth of compelling epidemiological data on its prevention is generally not available, and as a consequence, is largely unknown to the public. The purpose of this report is to review the epidemiological evidence of preventable causes of breast cancer. TABLE 1 Frequently used abbreviations and terms (listed alphabetically)AbbreviationsTermsABC linkAbortion–breast cancer linkCEE(s)Conjugated equine estrogen(s)CHDCoronary heart diseaseCHRTCombined hormone replacement therapyCIConfidence IntervalCOC(s)Combined oral contraceptive(s)ECEmergency contraceptionECP(s)Emergency contraception pill(s)ERTEstrogen replacement therapyFDAFood and Drug AdministrationFFTPFirst full-term pregnancyHRTHormone replacement therapyIA(s)Induced abortion(s)IARCInternational Agency for Research on CancerMPAMedroxyprogesterone acetateOC(s)Oral contraceptive(s)OROdds ratioOTCOver-the-counterPOC(s)Progestin-only contraceptive(s)RRRelative RiskWHIWomen's Health InitiativeWHOWorld Health Organization PMID:25249706

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds.

PubMed

Smith, E E; Angstadt, S; Monteiro, N; Zhang, W; Khademhosseini, A; Yelick, P C

2018-06-01

Tooth loss is a significant health issue currently affecting millions of people worldwide. Artificial dental implants, the current gold standard tooth replacement therapy, do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Here we propose bioengineered tooth buds as a superior alternative tooth replacement therapy. We describe improved methods to create highly cellularized bioengineered tooth bud constructs that formed hallmark features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells, and mineralized dental tissue formation. These constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats. To our knowledge, this is the first report describing the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development. We propose future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.