Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis.

PubMed

Andrès, E; Kurtz, J E; Perrin, A E; Dufour, P; Schlienger, J L; Maloisel, F

2001-08-01

Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA. Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count <0.5x10(9)/l) were extracted from a cohort study of DIA patients (n=110). G-CSF (300 microg/day subcutaneously) was used where the neutrophil count was <0.1x10(9)/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07+/-0.1x10(9)/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs. 11.6+/-5; 7.5+/-3.8 days vs. 12+/-4.5; and 7.3+/-4.8 days vs. 13+/-6.1, respectively (all p<0.05). G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.

Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

PubMed

Mijnhout, G S; Franken, A A M

2008-06-01

In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

Epidemiology, management and outcomes of Graves' disease-real life data.

PubMed

Hussain, Y S; Hookham, J C; Allahabadia, A; Balasubramanian, S P

2017-06-01

Treatment options in Graves' disease are clearly defined, but management practices and the perceptions of success are varied. The outcomes of treatment in large consecutive cohorts of Graves' disease have not been well characterised. The study describes the epidemiology, management strategies and medium term outcomes following anti-thyroid drug treatment, radio-iodine ablation and surgery in Graves' disease. All patients (n = 659) who received treatment for a new diagnosis of Graves' disease in secondary care over a 5 year period were included with a median (interquartile range) follow-up of 42.9 (29-57.5) months. The age adjusted incidence of adult onset Graves' disease in Sheffield, UK was 24.8 per 100,000 per year. Excluding 35 patients lost to follow-up, 93.1% (n = 581) were controlled on anti-thyroid drug treatment. Of these, 73.6% went into remission following withdrawal of anti-thyroid drugs; 5.2% were still undergoing initial therapy; 13.3% lost control whilst on anti-thyroid drugs; and 7.9% went on to have either surgery or radio-iodine ablation whilst controlled on anti-thyroid drugs. Of the 428 patients who achieved remission, 36.7% relapsed. Of 144 patients who had radio-iodine ablation treatment, 5.6% relapsed and needed further treatment. Of 119 patients having surgery, 5.2% had long-term hypoparathyroidism and none had documented long-term recurrent laryngeal nerve palsy. In the follow-up, 39.9% of patients underwent surgery or radio-iodine ablation with little morbidity. Up to two-thirds of patients who achieved remission did not relapse. Data on effectiveness and risks of treatments for Graves' disease presented in this study will help clinicians and patients in decision making.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

PubMed Central

Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves’ disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss. PMID:29621332

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves' disease.

PubMed

Mizuguchi, Yuki; Morimoto, Satoshi; Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi; Ichihara, Atsuhiro

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves' Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves' disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves' disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves' disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves' disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

Rethinking antithyroid drugs in pregnancy.

PubMed

Napier, C; Pearce, S H S

2015-04-01

Uncontrolled hyperthyroidism in pregnancy poses a risk to both mother and foetus, and the optimal treatment strategy in this setting remains elusive. Instigation of pharmacological therapy or an alternative intervention during pregnancy requires careful consideration, and the evidence that has underpinned our choice of antithyroid drug has not been robust. Recent research developments have prompted us to question our practice, and reconsider our approach to managing this patient group. © 2014 John Wiley & Sons Ltd.

Synthesis and structural characterization of some trisulfide analoges of thiouracil-based antithyroid drugs

NASA Astrophysics Data System (ADS)

Bhabak, Krishna P.; Bhowmick, Debasish

2012-08-01

Thiourea-based antithyroid drugs are effectively used for the treatment of hyperthyroidism. In this paper, we describe the synthesis of new trisulfides (11-12) from the commonly used thiourea-based antithyroid drugs such as 6-n-propyl-2-thiouracil (PTU) and 6-methyl-2-thiouracil (MTU) in the reaction with I2/KI system. Structural analysis by single crystal X-ray diffraction studies revealed the stabilization of trisulfides by a lactam-lactim tautomerism facilitating effective intramolecular as well as intermolecular non-covalent interactions. Although the structures of both trisulfides were found to be quite similar, a notable difference in the intermolecular interactions was observed between compounds 11 and 12 leading to different structural patterns. Structural stabilization of these trisulfides by tautomerism followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule.

Antithyroid drug induced a granulocytosis: what still we need to learn?

PubMed

Chaudhry, Liaqat Ali; Mauzen, Khalid Fouad; Ba-Essa, Ebtesam; Robert, Asirvatham Alwin

2016-01-01

Antithyroid drugs (ATDs) induced agranulocytosis is a rare but life threatening condition. We report a 29 years Filipino female diagnosed as having hyperthyroidism with normal base line blood counts, liver and renal profile. She was started on maximum 60 mg (20mg TID) oral dose of carbimazole since one month by her treating physician. Exactly after one month of treatment she presented to emergency room (ER) with fever, sore throat and generalized weakness for several days.

Antithyroid drug induced agranulocytosis: what still we need to learn ?

PubMed Central

Chaudhry, Liaqat Ali; Mazen, Khalid Fouad; Ba-Essa, Ebtesam; Robert, Asirvatham Alwin

2016-01-01

Antithyroid drugs (ATDs) induced agranulocytosis is a rare but life threatening condition. We report a 29 years Filipino female diagnosed as having hyperthyroidism with normal base line blood counts, liver and renal profile. She was started on maximum 60mg (20mg TID) oral dose of carbimazole since one month by her treating physician. Exactly after one month of treatment she presented to emergency room (ER) with fever, sore throat and generalized weakness for several days. PMID:27200132

Graves' disease in a 3 year-old patient with agranulocytosis due to anti-thyroid drugs: Radioiodine ablation therapy as an effective alternative.

PubMed

Espinosa-Muñoz, E; Ramírez-Ocaña, D; Martín-García, A M; Ruiz-García, F J; Puentes-Zarzuela, C

The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with 131 I ablation therapy. The relevance of the article is that Graves' disease is uncommon in the paediatric age range (especially in children younger than 6 years old), and developing complications due to a possible late diagnosis. Agranulocytosis as a potentially serious adverse effect following the use of anti-thyroid drugs, and the few reported cases of ablation therapy with 131 I at this age, makes this case unique. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Diagnosis and treatment of Graves disease.

PubMed

Streetman, Darcie D; Khanderia, Ujjaini

2003-01-01

To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, beta-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies. Primary articles were identified through a MEDLINE search (1966-July 2000). Key word searches included beta-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy. Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include beta-blockers, inorganic iodide, and lithium. beta-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure. Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

PubMed

Dănciulescu Miulescu, R; Carşote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-09-15

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

Possible association between hyperthyroidism in pregnant women and obstructive congenital abnormalities of urinary tract in their offspring--a population-based case-control study.

PubMed

Bánhidy, Ferenc; Puhó, Erzsébet H; Czeizel, Andrew E

2011-02-01

The teratogenic potential of some antithyroid drugs is known, but the aim of the study was to estimate the risk of congenital abnormalities (CAs) in the offspring of pregnant women with hyperthyroidism with or without antithyroid drug treatment. Comparison of the occurrence of medically recorded hyperthyroidism who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of CAs, 1980-1996. Of 22,843 cases with congenital abnormalities, 71 (0.31%) while of 38,151 controls, 116 (0.30%) had mothers with hyperthyroidism. The rate of hyperthyroidism in the mothers of cases with different CAs and in the mothers of matched controls was compared. Preeclampsia-eclampsia occurred more frequently in pregnant women with hyperthyroidism without antithyroid treatment. The analysis of specific groups of CAs showed an association between hyperthyroidism in pregnant women and obstructive defects of urinary tract in their children. The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed the risk of antithyroid medication in these pregnant women.

Antithyroid drug-induced agranulocytosis.

PubMed

Sun, Ming-Tsung; Tsai, Chen-Hao; Shih, Kuang-Chung

2009-08-01

Antithyroid drugs are widely used to treat hyperthyroidism, especially Graves' disease, but they tend to cause agranulocytosis, which increases the mortality rate. Granulocyte colony-stimulating factor decreases the duration of recovery from agranulocytosis. We retrospectively studied cases of antithyroid drug-induced agranulocytosis over the past 10 years in a northern Taiwan medical center. A clinical evaluation was conducted, including a review of complete blood cell counts and differential counts. Four cases were included in this analysis. Agranulocytosis persisted in 2 cases despite a change in therapy from propylthiouracil to methimazole. Fever, sore throat, and diarrhea were common symptoms of agranulocytosis. Initial white blood cell counts ranged from 450 to 1,710/microL. Only 1 case had a positive result from a throat swab culture (Staphylococcus aureus). Three of 4 cases received granulocyte colony-stimulating factor therapy, and the recovery time ranged from 3 to 13 days. All of the patients recovered from agranulocytosis. We concluded that: (1) conducting a routine complete blood cell count is beneficial in alerting caregivers to the possibility of agranulocytosis; (2) educating patients about the common symptoms of agranulocytosis may contribute to an early diagnosis; (3) providing granulocyte colony-stimulating factor therapy to patients results in good prognosis; and (4) monitoring for cross-reactions between drugs should be performed to prevent further episodes of agranulocytosis.

Chinese herbal medicines for hyperthyroidism.

PubMed

Zen, X X; Yuan, Y; Liu, Y; Wu, T X; Han, S

2007-04-18

Hyperthyroidism is a disease in which excessive amounts of thyroid hormones circulate in the blood. Patients, among other things suffer from tachycardia, warm moist skin and raised body temperature. The treatment of hyperthyroidism includes symptom relief and therapy with antithyroid medications, radioiodine and thyroidectomy. Medicinal herbs are used alone or in combination with antithyroid agents to treat hyperthyroidism in China and some other countries. To assess the effects of Chinese herbal medicines for treating hyperthyroidism. Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library, the Chinese Biomedical Database. Randomised controlled trials comparing the effects of Chinese herbal medicines alone with Chinese herbal medicines combined with antithyroid drugs, radioiodine or both. Three authors interviewed authors of all potentially relevant studies by telephone to verify randomisation procedures. One author entered data into a data extraction form and another author verified the results of this procedure. Thirteen relevant trials with 1770 participants were included. All of them were of low quality. Fifty-two studies still need to be assessed because the original authors could not be interviewed. None of these trials analysed mortality, health related quality of life, economic outcomes or compliance. Compared to antithyroid drugs alone the results showed that Chinese herbal medicines combined with antithyroid drugs may offer benefits in lowering relapse rates, reducing the incidence of adverse effects, relieving symptoms, improving thyroid antibody status and thyroid function. Two trials investigated Chinese herbal medicine versus radioiodine and reported improvements in anxiety, tachycardia and heat intolerance. However, thyroid function - with the exception of restored thyroid stimulating hormone (TSH) - was not significantly altered. The results suggest that traditional Chinese herbal medicines added to other routine treatment have a therapeutic potential for people with hyperthyroidism. However, due to methodological limitations, we could not identify a well-designed trial to provide strong evidence for Chinese traditional herbal medicine in the treatment of hyperthyroidism. Thus, we currently cannot recommend any single preparation or formulation for clinical use.

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.

[Clinical application of alendronate for osteoporosis/osteopenia secondary to hyperthyroidism].

PubMed

Yang, Li-Juan; Shen, Fei-Xia; Zheng, Jing-Chen; Zhang, Hai-Ling

2012-02-01

To evaluate the efficacy and safety of alendronate for the treatment of osteoporosis/osteopenia secondary to hyperthyroidism. From April 2008 to November 2009, 27 patients with hyperthyroidism with osteoporosis/ osteopenia measured by dual energy X-ray absorptiometry (DXA) were included in this study, and then they were randomly divided into two groups (group A and group B) by simple random sampling. Group A consisted of 14 patients treated with antithyroid drug and caltrate D, the antithyroid drug change with thyroid function, and caltrate D 600 mg per day. Group B consisted of 13 patients treated with antithyroid drug, caltrate D and alendronate, antithyroid drug and caltrate D the same as group A, and alendronate 70 mg weekly. Meanwhile, 21 healthy voluntary adults were chosen as control group. And compared with the control group which was treated with nothing. Followed-up for one year, the bone mineral density (including T-score, Z-score, BMD) in lumbar spine (LS), femoral neck (FN) and distal radius (DR) and general information, were compared before and after treatment. BMD at FN and DR were significantly higher at 12 months after treatment than at the baseline in group A (P = 0.000); T-score, Z-score, and BMD at the LS, FN and DR were all significantly higher at 12 months after treatment than at the baseline in group B (P < 0.05), but these data could not arrive to normal level. In group A, the percentage increased in BMD at the LS, FN, and DR were (4.34 +/- 10.5)%, (3.21 +/- 1.38)%, (1.95 +/- 0.44)%, respectively, at 12 months after treatment. In group B, the percentage increased in BMD at the LS, FN, and DR were (6.10 +/- 8.12)%, (4.10 +/- 5.64)%, (3.10 +/- 3.23)%, respectively, at 12 months after treatment. There was significant difference in the rate of increase between two groups (P < 0.05). AKP decreased, weight, BMI increased, and thyroid function decreased, after treatment than those before in both of the two groups. (P < 0.05). Alendronate can significantly increase BMD in treating patients with hyperthyroidism and osteoporosis/osteopenia. Compared with anti-thyroid drugs alone, treatment with alendronate can obtain more clinical effect and also very safety.

Indefinite antithyroid drug therapy in toxic Graves’ disease: What are the cons

PubMed Central

Rajput, Rajesh; Goel, Vasudha

2013-01-01

Existing treatment modalities for Graves’ disease includes antithyroid drugs (ATDs), radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves’ disease after discussing this with the patient. PMID:24251229

Indefinite antithyroid drug therapy in toxic Graves' disease: What are the cons.

PubMed

Rajput, Rajesh; Goel, Vasudha

2013-10-01

Existing treatment modalities for Graves' disease includes antithyroid drugs (ATDs), radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves' disease after discussing this with the patient.

[Treatment of hyperthyroidism due to Graves' disease: what is the recommended antithyroid drug during pregnancy?].

PubMed

Caron, P

2013-05-01

Clinical hyperthyroidism during the first trimester of pregnancy due to Graves' disease can be associated with maternal, obstetrical and fetal complications, indicating an active treatment to restore normal thyroid function. Antithyroid drugs are the first line treatment in pregnant women with hyperthyroidism. Due to the increased congenital malformations reported in neonates after first-trimester carbimazole/methimazole treatment and propylthiouracil associated hepatotoxicity, the recommended treatment for pregnant women with hyperthyroid Graves' disease is propylthiouracil during the first trimester of pregnancy and following the first trimester, consideration should be given switching to carbimazole/methimazole during the second part of gestation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations

PubMed Central

Dănciulescu Miulescu, R; Carșote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-01-01

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves’ disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug’s withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy. PMID:24155785

Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves' Disease Previously Treated with Antithyroid Drugs.

PubMed

Kautbally, Shakeel; Alexopoulou, Orsalia; Daumerie, Chantal; Jamar, François; Mourad, Michel; Maiter, Dominique

2012-07-01

We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunoglobulins (TSI) in patients with Graves' disease. We retrospectively studied 80 patients initially treated with antithyroid drugs and requiring either RAI (8.3 ± 1.7 mCi of (131)I; n = 40) or TTx (n = 40) as second-line therapy. The TTx and RAI groups were not different, except for larger goiter, higher FT3 and more frequent Graves' orbitopathy at diagnosis in the surgery group (p < 0.05). A persistent remission of hyperthyroidism was observed in 97% of operated patients versus 73% of the RAI patients at 3 years (p < 0.01). TTx was followed by a rapid and steady decrease in TSI during the first 9 months, while a surge of antibodies was observed during the first 6 months after RAI, followed by a slow decrease over the next 18 months. At the last visit, high TSI levels were still observed in 18 and 60% of patients in the surgery and RAI groups, respectively (p < 0.001). TTx is more efficient than RAI to induce a rapid and permanent correction of hyperthyroidism and TSI decrease in patients previously treated with antithyroid drugs.

[Role of TSH receptor autoantibodies for the diagnosis of Graves' disease and for the prediction of the course of hyperthyroidism and ophthalmopathy. Recommendations of the Thyroid Section of the German Society of Endocrinology].

PubMed

Eckstein, Anja; Mann, Klaus; Kahaly, George J; Grussendorf, Martin; Reiners, Christoph; Feldkamp, Joachim; Quadbeck, Beate; Bockisch, Andreas; Schott, Matthias

2009-05-15

Graves' disease (GD) is the only autoimmune disease where autoantibodies stimulate the target organs. Among the most common clinical manifestations are hyperthyroidism and orbitopathy (GO). To ensure the diagnosis of autoimmune hyperthyroidism, activity of TSH receptor autoantibodies (TRAb) should be determined. Because of their significantly improved sensitivity and equal specificity, second-generation TRAb assays (activity given in IU/l) should be preferred over first-generation assays (activity given in U/l). During follow-up of antithyroid drug therapy it is possible to predict outcome for some patients with high chances if TRAb levels are high. On this basis, thyreoablative treatment (operation or radioiodine) can already be indicated before the 1st year of antithyroid drug treatment has passed. If TRAb antibody titers are > 10 IU/l, it is possible to predict outcome as early as 6 months after initiation of antithyroid drug therapy. Below a certain threshold, depending on the time point of measurement, no representative risk analyses are available for TRAbs. TRAb measurement is also helpful to determine the course of GO. This may guide the physician through crucial treatment decisions, especially if the patient is at risk of deterioration.

Remission of Grave's disease after oral anti-thyroid drug treatment.

PubMed

Ishtiaq, Osama; Waseem, Sabiha; Haque, M Naeemul; Islam, Najmul; Jabbar, Abdul

2009-11-01

To evaluate remission rate of anti-thyroid drug treatment in patients with Grave's disease, and to study the factors associated with remission. A cross sectional study. The Endocrine Department of the Aga Khan University Hospital, Karachi from 1999 to 2000. Seventy four patients of Grave's disease were recruited who were prescribed medical treatment. Grave's disease was diagnosed in the presence of clinical and biochemical hyperthyroidism along with anti-microsomal (AMA) and anti-thyroglobulin antibodies (ATA) and thyroid scan. These patients were prescribed oral anti-thyroid drugs using titration regime and followed at 3, 6, 12 and 18 months. Patients were categorized into two groups: "remission group" and "treatment failure group" and results were compared using a chi-square test, t-test and logistic regression model with significance at p < 0.05. A majority of the patients were females (62.6%, n=46). During the follow-up period of 18 months, 41.9% patients went into remission. Univariate analysis showed that the initial free T4 level was significantly different (p < 0.05) in patients in remission and treatment failure groups. Multivariate analysis showed only initial free T4 level was a significant predictor of outcome. Positive AMA patients (n=27) had higher treatment failure (odds ratio: 2.55: 95%, CI 0.69 - 9:31), although the difference was not statistically significant (p = 0.13). Remission rates with oral anti-thyroid agents is markedly high. Patients should be offered alternate treatment options to those who do not enter remission during a period of 12-18 months of treatment, those who develop relapse, and those who have aggressive disease on initial presentation.

Pancytopenia in a Patient with Grave's Disease.

PubMed

Loh, Huai Heng; Tan, Florence

2013-08-01

Pancytopenia can rarely complicate Grave's disease. It can be due to uncontrolled thyrotoxicosis or as a result of rare side effect of antithyroid medication. Pernicious anemia leading to Vitamin B12 deficiency is another rare associated cause. We report a case of a patient with Grave's disease and undiagnosed pernicious anemia whom was assumed to have antithyroid drug induced pancytopenia. Failure to recognize this rare association of pernicious anemia as a cause of pancytopenia had resulted in delay in treatment and neurological complication in our patient.

Effect of Goiter Dispersion Formula on Serum Cytokines in Hyperthyroidism Patients with Neurologic Manifestations of Graves' Disease: A Randomized Trial on 80 Cases.

PubMed

Tian, Wen-Hong; Wang, Ying; Yang, Rui; Hu, Hai-Bing

2018-05-01

This study is aimed to explore the combined use of goiter dispersion formula and antithyroid drugs in the treatment of patients with neurologic manifestations of Graves' disease by examining its modulating effects on patients' cytokines. A total of 80 patients with Graves' disease were randomly divided into treatment and control groups. Patients of the treatment group received goiter dispersion formula and antithyroid drugs (methimazole or propylthiouracil), whereas those of the control group received antithyroid drug alone. FT3, FT4, and TSH contents were detected by chemiluminescence immunoassay at pre- and post-treatment; interleukin (IL)-2, IL-8, and IL-17 serum levels before and after the treatment were detected by radioimmunoassay; thyroid B-mode ultrasound and liver and renal function tests were performed in all patients of both groups. An additional cohort of 40 healthy subjects was recruited for baseline measurement. All the enrolled patients completed the trial. The effective treatment rate was higher in the treatment group than in the control group, of which the difference was statistically significant (treatment group, 95%; control group, 75%, p < 0.01). For blood cytokine, before treatment, IL-2 was reduced whereas IL-8 and IL-17 were increased significantly in both groups of patients with Graves' disease comparing with those in healthy subjects (p < 0.01). For patients of the treatment group, after treatment, their IL-2 levels were increased (p < 0.01) with concomitant decreases in IL-8 and IL-17 levels (p < 0.05). There were no significant changes in blood cytokine levels before and after treatment in the control group. Goiter dispersion formula significantly improved the treatment outcomes of antithyroid drug in hyperthyroidism patients with neurologic manifestations of Graves' disease by modulating IL-2, IL-8, and IL-17. The data supported the rationale for the use of goiter dispersion formula in Graves' disease treatment.

Successful treatment of thyroid storm presenting as recurrent cardiac arrest and subsequent multiorgan failure by continuous renal replacement therapy.

PubMed

Park, Han Soo; Kwon, Su Kyoung; Kim, Ye Na

2017-01-01

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves' disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient's dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment. The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

Outcome Prediction of Treatment of Graves' Hyperthyroidism with Antithyroid Drugs.

PubMed

Piantanida, E; Lai, A; Sassi, L; Gallo, D; Spreafico, E; Tanda, M L; Bartalena, L

2015-09-01

Graves' disease is the most common cause of hyperthyroidism in iodine-replete areas and is ultimately due to antibodies interacting with the TSH receptor on thyroid follicular cells [TSH-receptor antibody (TRAb)]. Antithyroid drugs (ATDs) belonging to the family of thionamides are the first-line treatment in Europe. ATD treatment is commonly continued for 18-24 months. Its major limitation is the high rate of relapses after drug withdrawal. Factors particularly bound to subsequent relapses are the large thyroid volume, smoking habit, persistence of TRAb in the circulation at the end of treatment, and the post-partum period. Under these conditions, consideration should be given to a definitive therapy for hyperthyroidism (radioiodine treatment, thyroidectomy), particularly if the patient is at risk of cardiovascular complications that might be exacerbated by persistence or recurrence of hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

Hyperthyroidism

PubMed Central

2016-01-01

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves’ disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves’ disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. PMID:27038492

Hyperthyroidism.

PubMed

De Leo, Simone; Lee, Sun Y; Braverman, Lewis E

2016-08-27

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thyrotoxicosis.

PubMed

Franklyn, Jayne A; Boelaert, Kristien

2012-03-24

Thyrotoxicosis is a common disorder, especially in women. The most frequent cause is Graves' disease (autoimmune hyperthyroidism). Other important causes include toxic nodular hyperthyroidism, due to the presence of one or more autonomously functioning thyroid nodules, and thyroiditis caused by inflammation, which results in release of stored hormones. Antithyroid drugs are the usual initial treatment (thionamides such as carbimazole or its active metabolite methimazole are the drugs of choice). A prolonged course leads to remission of Graves' hyperthyroidism in about a third of cases. Because of the low remission rate in Graves' disease and the inability to cure toxic nodular hyperthyroidism with antithyroid drugs alone, radioiodine is increasingly used as first line therapy, and is the preferred choice for relapsed Graves' hyperthyroidism. Total thyroidectomy is an option in selected cases. Future efforts are likely to concentrate on novel and safe ways to modulate the underlying disease process rather than stopping excess thyroid hormone production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves' Disease Previously Treated with Antithyroid Drugs

PubMed Central

Kautbally, Shakeel; Alexopoulou, Orsalia; Daumerie, Chantal; Jamar, François; Mourad, Michel; Maiter, Dominique

2012-01-01

Aims We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunoglobulins (TSI) in patients with Graves' disease. Methods We retrospectively studied 80 patients initially treated with antithyroid drugs and requiring either RAI (8.3 ± 1.7 mCi of 131I; n = 40) or TTx (n = 40) as second-line therapy. Results The TTx and RAI groups were not different, except for larger goiter, higher FT3 and more frequent Graves' orbitopathy at diagnosis in the surgery group (p < 0.05). A persistent remission of hyperthyroidism was observed in 97% of operated patients versus 73% of the RAI patients at 3 years (p < 0.01). TTx was followed by a rapid and steady decrease in TSI during the first 9 months, while a surge of antibodies was observed during the first 6 months after RAI, followed by a slow decrease over the next 18 months. At the last visit, high TSI levels were still observed in 18 and 60% of patients in the surgery and RAI groups, respectively (p < 0.001). Conclusions TTx is more efficient than RAI to induce a rapid and permanent correction of hyperthyroidism and TSI decrease in patients previously treated with antithyroid drugs. PMID:24783007

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

PubMed

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

2017-10-06

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

Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study

PubMed Central

Chen, Pei-Lung; Shih, Shyang-Rong; Wang, Pei-Wen; Lin, Ying-Chao; Chu, Chen-Chung; Lin, Jung-Hsin; Chen, Szu-Chi; Chang, Ching-Chung; Huang, Tien-Shang; Tsai, Keh Sung; Tseng, Fen-Yu; Wang, Chih-Yuan; Lu, Jin-Ying; Chiu, Wei-Yih; Chang, Chien-Ching; Chen, Yu-Hsuan; Chen, Yuan-Tsong; Fann, Cathy Shen-Jang; Yang, Wei-Shiung; Chang, Tien-Chun

2015-01-01

Graves' disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10−32) and HLA-DRB1*08:03 (Pcombined=1.83 × 10−9) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10−21, 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals. PMID:26151496

Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study.

PubMed

Chen, Pei-Lung; Shih, Shyang-Rong; Wang, Pei-Wen; Lin, Ying-Chao; Chu, Chen-Chung; Lin, Jung-Hsin; Chen, Szu-Chi; Chang, Ching-Chung; Huang, Tien-Shang; Tsai, Keh Sung; Tseng, Fen-Yu; Wang, Chih-Yuan; Lu, Jin-Ying; Chiu, Wei-Yih; Chang, Chien-Ching; Chen, Yu-Hsuan; Chen, Yuan-Tsong; Fann, Cathy Shen-Jang; Yang, Wei-Shiung; Chang, Tien-Chun

2015-07-07

Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*08:03 (Pcombined=1.83 × 10(-9)) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.

Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge gaps.

PubMed

Koren, Gideon; Soldin, Offie

2006-02-01

Despite being a common condition in pregnancy, and despite propylthiouracil (PTU) being perceived as safer than methimazole, there are virtually no epidemiological controlled studies on malformation rate an neurobehavioral outcomes with the former. This knowledge gap must be filled to ensure fetal safety.

Clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis caused by antithyroid drugs.

PubMed

Noh, Jaeduk Yoshimura; Yasuda, Shigemitu; Sato, Shotaro; Matsumoto, Masako; Kunii, Yo; Noguchi, Yoshihiko; Mukasa, Koji; Ito, Kunihiko; Ito, Koichi; Sugiyama, Osamu; Kobayashi, Hiroshi; Nihojima, Shigeru; Okazaki, Masaru; Yokoyama, Shunji

2009-08-01

The clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis caused by antithyroid drugs are still unclear because most reports describe only a small number of patients. The objective was to analyze a large number of patients with MPO-ANCA-associated vasculitis to determine the time of onset, the drug and dose taken, the clinical symptoms, the relationship between the clinical symptoms and the MPO-ANCA titer, and the incidence. We analyzed 92 patients in whom the adverse reaction of MPO-ANCA-associated vasculitis was reported to Chugai Pharmaceutical, a company that markets antithyroid drugs. Of the 92 patients, 41 (44.6%) had single-organ failure, 32 (34.8%) had two-organ failure, 13 (14.1%), had three-organ failure, and two (2.2%) had four-organ failure. The number of organs involved was unknown in the other four patients (4.3%). The median time of onset was 42 months (range, 1-372 months) after starting drug treatment. The median dose at onset of MPO-ANCA-associated vasculitis was 15 mg/d (range, 2.5-45 mg/d) for methimazole and 200 mg/d (50-450 mg/d) for propylthiouracil. The severity and number of organs involved were not correlated with the MPO-ANCA titer. The incidence was between 0.53 and 0.79 patients per 10,000, and the ratio of the estimated incidences for methimazole and propylthiouracil was 1:39.2. The time of onset of MPO-ANCA-associated vasculitis and the dose at onset varied. The severity and number of organs involved were not correlated with the MPO-ANCA titer, indicating a need for vigilance even when the MPO-ANCA titer is only weakly positive.

Evaluation and Management of the Child with Thyrotoxicosis.

PubMed

Leung, Alexander K C; Leung, Alexander A C

2018-03-26

Uncontrolled thyrotoxicosis, especially in early infancy, may cause irreversible damage to the central nervous system as well as profound effects on the function of many organs. Thyrotoxicosis has multiple etiologies and treatment depends on the underlying etiology. An accurate diagnosis is essential so that appropriate treatment can be initiated without undue delay. To review in depth the evaluation, diagnosis, and treatment of children with thyrotoxicosis. A PubMed search was completed in Clinical Queries using the key terms "thyrotoxicosis" and "hyperthyroidism". The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key terms "thyrotoxicosis" and "hyperthyroidism" from www.freepatentsonline.com and www.google.com/patents. Graves' disease accounts for approximately 96% of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma, pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug-induced thyrotoxicosis. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. The underlying cause of thyrotoxicosis should be treated if possible. Treatment options for Graves' disease include antithyroid medications, radioiodine therapy, and surgery. Recent patents related to the management of thyrotoxicosis are discussed. Currently, antithyroid medications are considered to be the initial treatment of choice for Graves' disease in the pediatric age group. Radioactive iodine treatment is generally used for children with poor compliance with antithyroid medications, children not in remission after 1 to 2 years of antithyroid medications, and children with a major adverse effect while receiving an antithyroid medication. Total or near-total thyroidectomy should be considered in children younger than 5 years of age who do not respond to or experience a major adverse effect to antithyroid medications. Surgery should also be considered in those with very large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in spite of treatment with antithyroid medications and radioactive iodine, and personal preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves' disease.

PubMed

Fukao, Atsushi; Takamatsu, Junta; Murakami, Yasuhiro; Sakane, Sadaki; Miyauchi, Akira; Kuma, Kanji; Hayashi, Shunichiro; Hanafusa, Toshiaki

2003-05-01

The relationship between emotional stress and the onset of hyperthyroidism has been well investigated, but the relationship between psychological factors and prognosis of antithyroid drug-treated hyperthyroidism is not well known. This study has examined not only emotional stresses but also patients' personality traits using specific tests. A prospective cohort study. Sixty-nine patients with hyperthyroid Graves' disease in the euthyroid state after 2-5 years of antithyroid drug therapy and 32 healthy subjects as the control group. Patients responded to three types of questionnaires, including the Minnesota Multiphasic Personality Inventory for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses. In the Graves' disease patients, stress scores of life events correlated significantly with serum TSH receptor antibody activity (r = 0.424, P < 0.001) and thyroid volume (r = 0.480, P < 0.001). When the patients were divided according to prognosis (41 with relapse and 28 with remission), four personality traits including hypochondriasis, depression, paranoia and psychasthenia (mental fatigue) were significantly (P = 0.0146, 0.0052, 0.0125, and 0.0186, respectively) more common in the relapsed Graves' disease group than those of the remitted group. Six personality traits of conversion hysteria, psychopathic deviation, masculinity and feminity, schizophrenia, hypomania, and social introversion were not significantly different between the two groups. The scores of daily hassles (problems of daily life) were also significantly (P = 0.0124) greater in the relapsed Graves' disease group than in the remitted group. The scale scores of depression and psychasthenia showed a positive correlation with scores of daily hassles (r = 0.535, P < 0.0001; r = 0.580, P < 0.0001, respectively), while an inverse correlation with scores of daily uplifts (r = -0.373, P = 0.0332; r = -0.322, P = -0.0120, respectively). The results suggest that major life events, personality traits of hypochondriasis and depression, paranoia, mental fatigue, and daily problems aggravate the prognosis of antithyroid drug-treated hyperthyroidism. Escape from life events is virtually impossible; thus coping strategies suggested by the physician may be useful in improving prognosis in Graves' disease.

Graves hyperthyroidism and pregnancy: a clinical update.

PubMed

Patil-Sisodia, Komal; Mestman, Jorge H

2010-01-01

To provide a clinical update on Graves' hyperthyroidism and pregnancy with a focus on treatment with antithyroid drugs. We searched the English-language literature for studies published between 1929 and 2009 related to management of hyperthyroidism in pregnancy. In this review, we discuss differential diagnosis of hyperthyroidism, management, importance of early diagnosis, and importance of achieving proper control to avoid maternal and fetal complications. Diagnosing hyperthyroidism during pregnancy can be challenging because many of the signs and symptoms are similar to normal physiologic changes that occur in pregnancy. Patients with Graves disease require prompt treatment with antithyroid drugs and should undergo frequent monitoring for signs of fetal and maternal hyperthyroidism and hypothyroidism. Rates of maternal and perinatal complications are directly related to control of hyperthyroidism in the mother. Thyroid receptor antibodies should be assessed in all women with hyperthyroidism to help predict and reduce the risk of fetal or neonatal hyperthyroidism or hypothyroidism. The maternal thyroxine level should be kept in the upper third of the reference range or just above normal, using the lowest possible antithyroid drug dosage. Hyperthyroidism may recur in the postpartum period as Graves disease or postpartum thyroiditis; thus, it is prudent to evaluate thyroid function 6 weeks after delivery. Preconception counseling, a multidisciplinary approach to care, and patient education regarding potential maternal and fetal complications that can occur with different types of treatment are important. Preconception counseling and a multifaceted approach to care by the endocrinologist and the obstetric team are imperative for a successful pregnancy in women with Graves hyperthyroidism.

Hyperthyroidism in pregnancy.

PubMed

Nygaard, Birte

2015-01-21

Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism in pregnancy are Graves' disease and chorionic gonadotrophin (hCG)-mediated hyperthyroidism. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of antithyroid drug treatments for hyperthyroidism in pregnancy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found no studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antithyroid drugs (carbimazole/thiamazole and propylthiouracil).

Necrotizing gingivostomatitis and osteonecrosis associated with antithyroid drug propylthiouracil therapy.

PubMed

Xing, Haixia; Guan, Xiaobing

2015-02-01

A 43-year-old Chinese female had been diagnosed with hyperthyroidism 15 years ago. She was recently administered 150 mg/day propylthiouracil (PTU). After 3 weeks of PTU administration, she developed necrotizing stomatitis and osteonecrosis, most likely due to secondary effects from the PTU treatment. Her neutrophil count was reduced below normal to 0.24×10(9)/L but normalized after withdrawal of PTU therapy. About 1 month after onset, the patient came to our hospital and began to receive intravenous treatments of metronidazole and amoxicillin. Following review of her medical history and a series of clinical and laboratory examinations, the patient was diagnosed with secondary necrotizing gingivostomatitis and osteonecrosis possibly associated with PTU-induced agranulocytosis. One-year after treatment, the patient's oral manifestations remained unchanged. This case demonstrates the need for dental practitioners to more closely monitor oral symptoms in patients with hyperthyroidism treated with antithyroid drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem?

PubMed

Balavoine, Anne-Sophie; Glinoer, Daniel; Dubucquoi, Sylvain; Wémeau, Jean-Louis

2015-12-01

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

Role of halogen and hydrogen bonds for stabilization of antithyroid drugs with hypohalous acids (HOX, X = I, Br, and Cl) adducts

NASA Astrophysics Data System (ADS)

El-Sheshtawy, Hamdy S.; El-Mehasseb, Ibrahim

2017-11-01

The mechanism for the inhibition of thyroid hormones by the thioamide-like antithyroid drug is a key process in the thyroid gland function. Therefore, in this study theoretical investigation of the molecular interaction between two antithyroid drugs, namely methimazol (MMI) and thiazoline-2-thione (T2T), with the hypohalous acids (HOX, X = I, Br, and Cl), which act as heme-linked halogenated species to tyrosine residue was discussed. The calculations were performed by M06-2X and MP2 using aug-cc-pVDZ level of theory. In addition, wB97xd/6-31G* level of theory was used in order to account for the dispersion forces. The results show the possible formation of three adducts, which is stabilized by halogen bond (I), both halogen and hydrogen bonds (II), two hydrogen bonds (III). The binding energies of the complexes reveals stabilization in the order III > II > I. The binding energies of the complexes was increased with increasing the electron affinity and polarizability of halogen atom, the dipole moment of the complexes (I and II), the electrostatic potential on halogen atom (Vmax:i.e σ-hole), and the charge-transfer process through the halogen bond in I. On the other hand, the binding energies of the complexes decreased with increasing the halogen atom electronegativity and the dipole moment of complex III. Natural bond orbital (NBO) analysis was used to investigate the molecular orbital interactions and the charge transfer process upon complexation.

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.

Shifts in propylthiouracil and methimazole prescribing practices: antithyroid drug use in the United States from 1991 to 2008.

PubMed

Emiliano, Ana B; Governale, Laura; Parks, Mary; Cooper, David S

2010-05-01

The thionamide antithyroid drugs methimazole and propylthiouracil are the mainstay of pharmacologic therapy for Graves' disease. However, little is known about the rate of use of these drugs and the prescribing practices of physicians treating hyperthyroidism. The objective of the study was to examine the frequency of methimazole and propylthiouracil use from years 1991 to 2008. The data were acquired by the U.S. Food and Drug Administration's Division of Epidemiology through two databases: IMS National Sales Perspectives and the Surveillance Data, Inc. Vector One: National database. There was a 9-fold increase in the annual number of methimazole prescriptions during the study period, from 158,000 to 1.36 million per year. There was a 19% increase in the annual number of propylthiouracil prescriptions, from 348,000 to 415,000 per year. Propylthiouracil, which held two thirds of the market from 1991 to 1995, was surpassed by methimazole in 1996. Patient demographic data indicated that although 72% of methimazole prescriptions were for females, males were more likely to be on methimazole (82%) than females (74%) (P < 0.001, two tailed chi(2) test). The only demographic group in which methimazole use decreased was women of child-bearing age (5% decrease, P < 0.001, two tailed chi(2)). The incidence of hyperthyroidism in 2008 was estimated based on the number of new prescriptions of thionamides by age group and data from the 2008 U.S. census: 0.44 per 1000 for ages 0-11 yr, 0.26 per 1000 for ages 12-17 yr, 0.59 per 1000 for ages 18-44 yr, 0.78 per 1000 for ages 45-64 yr, and 1.01 per 1000 for ages 65+ yr. Methimazole has become the most frequently prescribed antithyroid drug. The remarkable increase in the total number of dispensed thionamide prescriptions over the last 18 yr may indicate a trend toward pharmacological treatment as primary treatment of Graves' disease in the United States.

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

PubMed Central

Rapoport, Basil

2013-01-01

Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves' disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition. The occurrence of “switching” emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare “switch” patients and appropriate Graves' and Hashimoto's controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity. PMID:23025526

Serum chromogranin A concentration in hyperthyroidism before and after medical treatment.

PubMed

Al-Shoumer, Kamal A S; Vasanthy, Bagavathy A

2009-07-01

The aim was to evaluate changes in chromogranin A (CgA) concentration in hyperthyroidism and to assess its metabolic correlations. We studied CgA levels in hyperthyroidism. First, 38 hyperthyroid patients matched with 86 normal controls were studied after an overnight fast. Second, 30 if the 38 patients were followed up for 6 months with medical antithyroid drug therapy (carbimazole). In the first study, after 10-12 h overnight fasting, blood was collected for measurement of CgA, glucose, insulin, intact proinsulin, and thyroid function. These variables were remeasured in the second study for the patients after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months. Pretreatment CgA level was significantly higher in patients compared with controls. CgA levels dropped significantly to levels similar to those of controls after antithyroid therapy. Although baseline and follow-up fasting glucose, insulin, and intact proinsulin demonstrated similar pattern of CgA changes before and after medical treatment, CgA did not correlate with any of them. However, CgA levels demonstrated a significant positive correlation with free T(3) and free T(4) only. These studies demonstrate that untreated hyperthyroidism is associated with elevated CgA level that changes in parallel to thyroid status. It is therefore possible to use CgA concentration as a potential marker of disease activity in hyperthyroidism.

Diffuse alveolar haemorrhage secondary to propylthiouracil-induced vasculitis

PubMed Central

Ferreira, Catarina; Costa, Teresa; Marques, Ana Vieira

2015-01-01

Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy. PMID:25661751

Antibodies to Actin in Autoimmune Neutropenia

DTIC Science & Technology

1990-02-01

S) 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Dept of Hematology (If applicable) Div of Medicine ...ceph- standard deviations above the mean value for 20 normal serum alosporins, phenothiazines, antithyroid drugs, antiarrythmic controls reflecting

Effects of prenatal exposure to antithyroid drugs on imprinting behavior in chicks.

PubMed

Kagami, Keisuke; Nishigori, Hidekazu; Nishigori, Hideo

2010-09-01

Thyroid hormones play important roles in vertebrate brain development. However, there is little understanding of the direct effects of fetal thyroid dysfunction, i.e., not acquired through the mother, on learning ability. In the present study, we use a chick embryo as a fetal model to investigate the effects of prenatal exposure to antithyroid drugs on imprinting behavior in hatched chicks. Methimazole (MMI) at 20micromol/egg or 5micromol/egg of propylthiouracil (PTU) was administered to eggs on day 14 while the control was given only a vehicle. An imprinting test was conducted after the chicks hatched. Day-old chicks were exposed to a rotating training object for 150min. The next day, the trained chicks were exposed to the training object and a novel object. The imprinting preference was represented as a preference score (PS) calculated as the rate of following the training object to following the training and novel objects. In the MMI-treated chicks, the PS was 0.68+/-0.06 (range, 0.38-0.88), which was significantly lower than that in the control chicks (0.86+/-0.04, p<0.01). In the PTU-treated chicks, the PS was 0.69+/-0.04 (range, 0.52-0.89), which was also significantly lower than that in the control (0.88+/-0.02, p<0.001). The present findings suggested that fetal thyroid dysfunction inhibited brain development, leading to impaired learning and memory. Our chick model can be considered useful for investigating the direct effects of prenatal exposure to antithyroid drugs or substances in the environment on learning ability after birth. Copyright 2010 Elsevier Inc. All rights reserved.

131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment.

PubMed

Ding, Yong; Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

2016-02-01

The aim of this study is to evaluate the safety and long-term results of (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with (131)I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to (131)I therapy, all patients were given low-iodine diet. The dose of (131)I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total (131)I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. © 2015 by the Society for Experimental Biology and Medicine.

131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment

PubMed Central

Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

2015-01-01

The aim of this study is to evaluate the safety and long-term results of 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with 131I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to 131I therapy, all patients were given low-iodine diet. The dose of 131I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total 131I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. PMID:26341470

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

PubMed

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

2017-04-02

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

Thyroxine, shape, and weight: interaction of Graves' disease and bulimia nervosa.

PubMed

Teufel, Martin; Giel, Katrin Elisabeth; Lehr, Jule; Becker, Sandra; Muthig, Michaela; Zipfel, Stephan; Kuprion, Jürgen

2013-03-01

A case of a 25-year-old woman with bulimia nervosa and Graves' disease is presented. Graves' disease is the cause of 50-80 % of hyperthyroidism. The disease is characterized by increases of thyroid hormone production, activation of the metabolism, and successive weight loss. Bulimia nervosa is characterized by purging behavior after binge eating episodes. We report a patient suffering from both entities. A pronounced non-compliance to the intake of antithyroid drugs (Carbimazole) correlated with eating disorder symptoms like negative evaluation of the body and fear of weight gain. Thus, elevated hyperthyroidism due to Graves' disease served as a purging method. During 8 weeks of inpatient psychotherapy, the patient adapted to a structured eating behavior. Self-esteem was less influenced by body shape and body weight, and compliance to endocrinological recommendations improved. Non-compliance to antithyroid drugs may be a symptom of an eating disorder. A careful and primarily non-confronting interdisciplinary diagnostic and treatment approach is required.

Cholestasis and protein-losing enteropathy secondary to hyperthyroidism in a 6-year-old girl.

PubMed

Gargouri, Lamia; Charfi, Manel; Maalej, Bayen; Majdoub, Imen; Safi, Faiza; Fourati, Hela; Hentati, Yosr; Daoud, Emna; Mnif, Zeineb; Abid, Mohamed; Mahfoudh, Abdelmajid

2014-09-01

Hepatic dysfunctions are not infrequent in patients with hyperthyroidism. These disorders may be related to the effects of the excess thyroid hormone secretion, to the uses of antithyroid drugs, or to the presence of concomitant hepatic diseases. Our aim is to describe the clinical and biochemical features of liver dysfunction related to thyrotoxicosis. We report here a case of a 6-year-old girl who was admitted for jaundice and pruritus as a result of the development of hyperthyroidism due to Graves' disease. On physical examination at admission, she was found to have jaundice and hepatomegaly. Laboratory data show cholestasis and protein-losing enteropathy. Investigations exclude other causes of hepatic disorder. One month after the initiation of antithyroid drug, the patient became euthyroid with improvement in jaundice and pruritus and normalization of hepatic tests and alpha antitrypsine clearance. In conclusion, the diagnosis of hyperthyroidism may be delayed in patients in whom the primary manifestations were pruritus and jaundice. The physician should suspect thyrotoxicosis prior to hepatitis or skin manifestations.

Management of Hyperthyroidism during the Preconception Phase, Pregnancy, and the Postpartum Period.

PubMed

Sarkar, Sudipa; Bischoff, Lindsay A

2016-11-01

Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation.

PubMed

Yoshihara, Ai; Noh, JaedukYoshimura; Yamaguchi, Takuhiro; Ohye, Hidemi; Sato, Shiori; Sekiya, Kenichi; Kosuga, Yuka; Suzuki, Miho; Matsumoto, Masako; Kunii, Yo; Watanabe, Natsuko; Mukasa, Koji; Ito, Kunihiko; Ito, Koichi

2012-07-01

Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy. We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women. We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations. The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation. In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

Hyperthyroidism (primary)

PubMed Central

2008-01-01

Introduction Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy. PMID:19450325

Hyperthyroidism (primary)

PubMed Central

2010-01-01

Introduction Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy. PMID:21418670

Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

EPA Science Inventory

Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves' disease.

PubMed

Léger, Juliane; Carel, Jean-Claude

2017-08-01

Graves' disease is an autoimmune disorder. It is the leading cause of hyperthyroidism, but is rare in children. Patients are initially managed with antithyroid drugs (ATDs), such as methimazole/carbimazole. A major disadvantage of treatment with ATD is the high risk of relapse, exceeding 70% of children treated for duration of 2 years, and the potential major side effects of the drug reported in exceptional cases. The major advantage of ATD treatment is that normal homeostasis of the hypothalamus-pituitary-thyroid axis may be restored, with periods of drug treatment followed by freedom from medical intervention achieved in approximately 40-50% of cases after prolonged treatment with ATD, for several years, in recent studies. Alternative ablative treatments such as radioactive iodine and, less frequently and mostly in cases of very high volume goiters or in children under the age of 5 years, thyroidectomy, performed by pediatric surgeons with extensive experience should be proposed in cases of non-compliance, intolerance to medical treatment or relapse after prolonged medical treatment. Ablative treatments are effective against hyperthyroidism, but they require the subsequent administration of levothyroxine throughout the patient's life. This review considers data relating to the prognosis for Graves' disease remission in children and explores the limitations of study designs and results; and the emerging proposal for management through the prolonged use of ATD drugs. © 2017 European Society of Endocrinology.

Methimazole associated eosinophilic pleural effusion: a case report.

PubMed

Gaspar-da-Costa, Pedro; Duarte Silva, Filipa; Henriques, Júlia; do Vale, Sónia; Braz, Sandra; Meneses Santos, João; M M Victorino, Rui

2017-03-21

Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.

Antithyroid Drug Therapy for Graves' Disease and Implications for Recurrence

PubMed Central

Fu, Jing; Xu, Yuan

2017-01-01

Graves' disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment. PMID:28529524

Shifts in Propylthiouracil and Methimazole Prescribing Practices: Antithyroid Drug Use in the United States from 1991 to 2008

PubMed Central

Emiliano, Ana B.; Governale, Laura; Parks, Mary; Cooper, David S.

2010-01-01

Context: The thionamide antithyroid drugs methimazole and propylthiouracil are the mainstay of pharmacologic therapy for Graves’ disease. However, little is known about the rate of use of these drugs and the prescribing practices of physicians treating hyperthyroidism. Objective: The objective of the study was to examine the frequency of methimazole and propylthiouracil use from years 1991 to 2008. Methods: The data were acquired by the U.S. Food and Drug Administration’s Division of Epidemiology through two databases: IMS National Sales Perspectives and the Surveillance Data, Inc. Vector One: National database. Results: There was a 9-fold increase in the annual number of methimazole prescriptions during the study period, from 158,000 to 1.36 million per year. There was a 19% increase in the annual number of propylthiouracil prescriptions, from 348,000 to 415,000 per year. Propylthiouracil, which held two thirds of the market from 1991 to 1995, was surpassed by methimazole in 1996. Patient demographic data indicated that although 72% of methimazole prescriptions were for females, males were more likely to be on methimazole (82%) than females (74%) (P < 0.001, two tailed χ2 test). The only demographic group in which methimazole use decreased was women of child-bearing age (5% decrease, P < 0.001, two tailed χ2). The incidence of hyperthyroidism in 2008 was estimated based on the number of new prescriptions of thionamides by age group and data from the 2008 U.S. census: 0.44 per 1000 for ages 0–11 yr, 0.26 per 1000 for ages 12–17 yr, 0.59 per 1000 for ages 18–44 yr, 0.78 per 1000 for ages 45–64 yr, and 1.01 per 1000 for ages 65+ yr. Conclusions: Methimazole has become the most frequently prescribed antithyroid drug. The remarkable increase in the total number of dispensed thionamide prescriptions over the last 18 yr may indicate a trend toward pharmacological treatment as primary treatment of Graves’ disease in the United States. PMID:20335447

Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer.

PubMed

Zhong, Yi-ping; Ying, Ying; Wu, Hai-tao; Zhou, Can-quan; Xu, Yan-wen; Wang, Qiong; Li, Jie; Shen, Xiao-ting; Li, Jin

2012-01-01

To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.

Relationship between Antithyroid Antibody and Pregnancy Outcome following in Vitro Fertilization and Embryo Transfer

PubMed Central

Zhong, Yi-ping; Ying, Ying; Wu, Hai-tao; Zhou, Can-quan; Xu, Yan-wen; Wang, Qiong; Li, Jie; Shen, Xiao-ting; Li, Jin

2012-01-01

Objective: To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). Methods: A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. Results: There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Conclusion: Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET. PMID:22253557

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

PubMed

Keklik, Muzaffer; Kaynar, Leylagul; Yilmaz, Mehmet; Sivgin, Serdar; Solmaz, Musa; Pala, Cigdem; Aribas, Sulbiye; Akyol, Gulsah; Unluhizarci, Kursat; Cetin, Mustafa; Eser, Bulent; Unal, Ali

2013-06-01

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (p<0.001) and free triiodotyhronin (FT3) (p<0.004) levels. There was statistically significant increase in the mean values of TSH levels after TPE (p<0.001). Clinical improvement was achieved in hyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relapse following antithyroid drug therapy for Graves' hyperthyroidism.

PubMed

Laurberg, Peter; Krejbjerg, Anne; Andersen, Stine Linding

2014-10-01

In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Interaction of Thioamides, Selenoamides, and Amides With Diiodine

PubMed Central

Hadjikakou, Sotiris K.; Hadjiliadis, Nick

2006-01-01

We review the results of our work on the iodine interaction with thioamides, selenoamides, and amides. Complexes with (i) “spoke” or “extended spoke” structures, D · I2 and D · I2 · I2, respectively, (D is the ligand donor) (ii) iodonium salts of {[D2 − I]+[In]−} (n = 3, 7) and {[D2 − I]+[FeCl4]−} formulae and (iii) disulfides of the categories (a) [D − D], (b) {[D − DH]+[I3]−} have been isolated and characterized. A compound of formula {[D2 − I]+[I3]−[D · I2]} containing both types of complexes (i) and (ii) was also isolated. The interaction of diiodine with selenium analogs of the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU (6-alkyl-2-Selenouracil) results in the formation of complexes with formulae [(RSeU)I2]. All these results are correlated with the mechanism of action of antithyroid drugs. Finally, we review here our work on the diiodine interaction with the amides (LO). PMID:17497011

Allergic reactions to antithyroid drugs are associated with autoimmunity a retrospective case-control study.

PubMed

Chivu, R D; Chivu, Laura Ioana; Ion, Daniela Adriana; Barbu, Carmen; Fica, Simona

2006-01-01

Thiamazole is the most used antithyroid drug for thyrotoxicosis in Basedow-Graves' (BG) (autoimmune) disease and in toxic multinodular goitre (TMG) (non-autoimmune). This study aims to find whether allergic reactions to thiamazole occur more frequently during the treatment of BG than of TMG. Retrospective study, of 128 patients newly diagnosed and treated for thyrotoxicosis in the first 6 months of 2006, in the Endocrinology Department of "Elias" Hospital, Bucharest. Cases were all patients treated with thiamazole who developed allergic reactions. Controls were all patients treated with thiamazole without allergic reactions. Risk factor was considered to be the presence of BG. Cases group consisted of 6 patients. All 6 started treatment with thiamazole for BG, and developed allergic reactions after 2-4 weeks of treatment. When thiamazole was withdrawn, allergic symptoms ceased under antihistamines and steroids. In order to control the thyrotoxicosis, antihistamines and oral steroids was administered, together with thiamazole in slow increasing doses. After about 4 weeks under this combination, a tolerance to thiamazole seems to appear. Control group consisted of 122 patients who started thiamazole: 66 for BG and 56 for TMG (without allergic reactions). Allergy to thiamazole was significantly associated with the autoimmune BG, and not with TMG (p = 0.03, OR = 11.04). None of the patients with TMG developed allergic reactions to the drug. Tolerance to this drug may occur.

Antithyroid arthritis syndrome.

PubMed

Modi, Anar; Amin, Hari; Morgan, Farah

2017-02-27

Antithyroid arthritis syndrome is a constellation of symptoms of myalgia, arthralgia, arthritis, fever and rash associated with the use of antithyroid medications. We report a case of a patient with severe hyperthyroidism likely secondary to Graves' disease who presented with the abovementioned symptoms after being treated with methimazole (antithyroid medication). Our aim is to increase awareness regarding this uncommon but disabilitating and life-threatening adverse effect of antithyroid medications among clinicians. We also discuss the proposed pathophysiology for this immunological reaction as well as management options in these patients. 2017 BMJ Publishing Group Ltd.

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.

Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves' disease in a middle-aged woman.

PubMed

Kamoi, K; Mitsuma, T; Sato, H; Yokoyama, M; Washiyama, K; Tanaka, R; Arai, O; Takasu, N; Yamada, T

1985-11-01

A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its alpha-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas beta-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. L-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH. Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, alpha-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its alpha-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour. It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.

Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

PubMed Central

Kurtoğlu, Selim; Özdemir, Ahmet

2017-01-01

Fetal and neonatal hyperthyroidism may occur in mothers with Graves’ disease. Fetal thyrotoxicosis manifestation is observed with the transition of TSH receptor stimulating antibodies to the fetus from the 17th–20th weeks of pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks. The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement in pregnancy and maternal treatment is conducted in accordance. The probability of neonatal hyperthyroidism is high in the babies of mothers that have ongoing antithyroid requirement and higher antibody levels in the last months of pregnancy. Clinical manifestation may be delayed by 7–17 days because of the antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be confused with sepsis and congenital viral infections. Herein, the diagnosis and therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism. PMID:28439194

Interventions for preventing and treating hyperthyroidism in pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2010-09-08

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 July 2010). We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Two review authors would have assessed trial eligibility and risk of bias, and extracted data. No trials were located. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

Birth defects observed with maternal carbimazole treatment: Six cases reported to Nice's Pharmacovigilance Center.

PubMed

Koenig, D; Spreux, A; Hiéronimus, S; Chichmanian, R-M; Bastiani, F; Fénichel, Patrick; Brucker-Davis, F

2010-12-01

To report cases of embryopathy occurring following first trimester exposure to anti-thyroid drugs. Retrospective screening of the database of our Pharmacovigilance Center from 1987 to date. We report six cases of embryopathy, all following carbimazole exposure during the first trimester: two cases of abdominal wall defect, including one associated with facial dysmorphia; one case of digestive malformation (patent omphalomesenteric duct); two cases of aplasia cutis including one with facial dysmorphism; one case of bilateral choanal atresia with aorta coarctation associated with poorly controlled insulin dependent diabetes. Four out of five patients were euthyroid with treatment during the first trimester. We found a context suggesting genetic predisposition to congenital malformation in three cases: two cases of parental cleft lip/palate, one case of consanguinity. Outcome was favorable in all cases. We want to raise awareness about the potential teratogenicity of carbimazole, probably on a predisposed genetic background. We suggest better reporting of congenital anomalies in children of women with Graves'disease, with or without in utero exposure to anti-thyroid drugs. In light of current literature, propylthiouracil should be the first line treatment for hyperthyroid women wishing a pregnancy. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Predictive Value of Gene Polymorphisms on Recurrence after the Withdrawal of Antithyroid Drugs in Patients with Graves’ Disease

PubMed Central

Liu, Jia; Fu, Jing; Duan, Yan; Wang, Guang

2017-01-01

Graves’ disease (GD) is one of the most common endocrine diseases. Antithyroid drugs (ATDs) treatment is frequently used as the first-choice therapy for GD patients in most countries due to the superiority in safety and tolerance. However, GD patients treated with ATD have a relatively high recurrence rate after drug withdrawal, which is a main limitation for ATD treatment. It is of great importance to identify some predictors of the higher recurrence risk for GD patients, which may facilitate an appropriate therapeutic approach for a given patient at the time of GD diagnosis. The genetic factor was widely believed to be an important pathogenesis for GD. Increasing studies were conducted to investigate the relationship between gene polymorphisms and the recurrence risk in GD patients. In this article, we updated the current literatures to highlight the predictive value of gene polymorphisms on recurrence risk in GD patients after ATD withdrawal. Some gene polymorphisms, such as CTLA4 rs231775, human leukocyte antigen polymorphisms (DRB1*03, DQA1*05, and DQB1*02) might be associated with the high recurrence risk in GD patients. Further prospective studies on patients of different ethnicities, especially studies with large sample sizes, and long-term follow-up, should be conducted to confirm the predictive roles of gene polymorphism. PMID:29085334

Hyperthyroidism in pregnancy.

PubMed

Cooper, David S; Laurberg, Peter

2013-11-01

Changes in thyroid hormone concentrations that are characteristic of hyperthyroidism must be distinguished from physiological changes in thyroid hormone economy that occur in pregnancy, especially in the first trimester. Approximately one to two cases of gestational hyperthyroidism occur per 1000 pregnancies. Identification of hyperthyroidism in a pregnant woman is important because adverse outcomes can occur in both the mother and the offspring. Graves' disease, which is autoimmune in nature, is the usual cause; but hyperthyroidism in pregnancy can be caused by any type of hyperthyroidism--eg, toxic multinodular goitre or solitary autonomously functioning nodule. Gestational transient thyrotoxicosis is typically reported in women with hyperemesis gravidarum, and is mediated by high circulating concentrations of human chorionic gonadotropin. Post-partum thyroiditis occurs in 5-10% of women, and many of those affected ultimately develop permanent hypothyroidism. Antithyroid drug treatment of hyperthyroidism in pregnant women is controversial because the usual drugs--methimazole or carbimazole--are occasionally teratogenic; and the alternative--propylthiouracil--can be hepatotoxic. Fetal hyperthyroidism can be life-threatening, and needs to be recognised as soon as possible so that treatment of the fetus with antithyroid drugs via the mother can be initiated. In this Review, we discuss physiological and pathophysiological changes in thyroid hormone economy in pregnancy, the diagnosis and management of hyperthyroidism during pregnancy, severe life-threatening thyrotoxicosis in pregnancy, neonatal thyrotoxicosis, and post-partum hyperthyroidism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Medical treatment of hyperthyroidism: state of the art.

PubMed

Fumarola, A; Di Fiore, A; Dainelli, M; Grani, G; Calvanese, A

2010-11-01

Methimazole (MMI) and propylthiouracil (PTU) are the main antithyroid drugs used for hyperthyroidism. They inhibit the synthesis of thyroid hormone at various levels and are used as the primary treatment for hyperthyroidism or as a preparation before radioiodine therapy or thyroidectomy. MMI is the drug of choice because of its widespread availability, longer half-life and small number of severe side effects. Drugs of second choice are potassium perchlorate, beta blockers, iodine, lithium carbonate and glucocorticoids. Rituximab, a monoclonal antibody directed against human CD20, was recently proposed as a biological therapy for cases of Graves' disease unresponsive to traditional drugs. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Predicting relapse of Graves' disease following treatment with antithyroid drugs

PubMed Central

LIU, LIN; LU, HONGWEN; LIU, YANG; LIU, CHANGSHAN; XUN, CHU

2016-01-01

The aim of the present study was to monitor long term antithyroid drug treatments and to identify prognostic factors for Graves' disease (GD). A total of 306 patients with GD who were referred to the Endocrinology Clinic at Weifang People's Hospital (Weifang, China) between August 2005 and June 2009 and treated with methimazole were included in the present study. Following treatment, patients were divided into non-remission, including recurrence and constant treatment subgroups, and remission groups. Various prognosis factors were analyzed and compared, including: Patient age, gender, size of thyroid prior to and following treatment, thyroid hormone levels, disease relapse, hypothyroidism and drug side-effects, and states of thyrotropin suppression were observed at 3, 6 and 12 months post-treatment. Sixty-five patients (21.2%) were male, and 241 patients (78.8%) were female. The mean age was 42±11 years, and the follow-up was 31.5±6.8 months. Following long-term treatment, 141 patients (46%) demonstrated remission of hyperthyroidism with a mean duration of 18.7±1.9 months. The average age at diagnosis was 45.6±10.3 years in the remission group, as compared with 36.4±8.8 years in the non-remission group (t=3.152; P=0.002). Free thyroxine (FT)3 levels were demonstrated to be 25.2±8.9 and 18.7±9.4 pmol/l in the non-remission and remission groups, respectively (t=3.326, P=0.001). The FT3/FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were both significantly higher in the non-remission group (t=3.331, 3.389, P=0.001), as compared with the remission group. Logistic regression analysis demonstrated that elevated thyroid size, FT3/FT4 ratio and TRAb at diagnosis were associated with poor outcomes. The ratio of continued thyrotropin suppression in the recurrent subgroup was significantly increased, as compared with the remission group (P=0.001), as thyroid function reached euthyroid state at 3, 6 and 12 months post-treatment. Patients with GD exhibiting large thyroids, high pre-mediation TRAb levels and elevated FT3/FT4 ratios responded less markedly to antithyroid drug treatments, as compared with patients not exhibiting these prognostic factors. Furthermore, patients with large thyroids, post-medication ophthalmopathy and continued thyrotropin suppression demonstrated higher rates of recurrence. PMID:27073464

Graves' disease in Albanian children.

PubMed

Gjikopulli, A; Tomori, Sonila; Kollçaku, L; Hoxha, P; Grimci, Lindita; Ylli, Zamira

2014-01-01

Graves' disease (GD) accounts for 10-15% of thyroid disorders in patients less than 18 years of age. It is the most common cause of thyrotoxicosis in children and accounts for at least 95% of cases in children. Pediatric Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. To review treatment outcome of pediatric Graves' disease in Albania. Descriptive review of 15 children with Graves' disease, diagnosed from Jan.2007 to Dec. 2013, at the Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Centre "Mother Teresa", Albania was performed. All patients, mean age 10.56 ± 3.37 years, (range 2.02-16.09 years) were presented with goiter and increased serum FT4, mean 39.80 ± 16.02 ng/mL, (range 21.0-74.70 ng/mL), serum FT3, mean 12.98 ± 3.45 pg/mL, (range 6.90 -17.90 pg/mL) and suppressed TSH levels, mean 0.02 ± 0.01 mUI/L, (range 0.01-0.05 mUI/L). Anti TSH Receptor were positive in 100% of patients mean value 6.51 ± 3.61 UI/mL (range 1.63 - 14.10 UI/mL). Anti-thyroglobulin and Anti-TPO antibodies were positive in 60% and 46.6% respectively. Clinical course of 15 patients after treatment with anti-thyroid drugs mainly MMI for 3.19 ± 1.48 (range 0.60 - 6.20) years is as follows: seven (46.66%) underwent remission, five out of seven (71.41%) who underwent remission, relapsed. Three of them (20%) were treated with I(131), and two (13.3%) underwent to total thyroidectomy. MMI was the most common first line therapy in the presented patients with Graves' disease. Remission rate was 46.66% after an average 1.48 ± 0.71 years (range 0.60 - 2.70 years) of treatment with anti-thyroid drugs. Remission period was 2.70 ± 0.36 years (2.1 - 3.1 years) Relapse occurred in 71.41% of patient. I(131) and thyroidectomy were used as second line therapy in the present study.

Personalised immunomodulating treatments for Graves' disease: fact or fiction?

PubMed

Struja, Tristan Mirko; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Müller, Beat; Schütz, Philipp

2017-08-14

Although Graves' disease has been recognised for more than 100 years, its physiopathological mechanisms are incompletely understood. Treatment strategies today mainly focus on suppression of thyroid hormone production by use of antithyroid drugs or radio-iodine, but neglect the underlying immunological mechanisms. Although Graves' disease is often seen as a prototype for an autoimmune mechanism, it is more likely to be a heterogeneous syndrome showing characteristics of both autoimmunity and immunodeficiency. The interplay of these two mechanisms may well characterise the physiopathology of this disease and its complications. Immunodeficiency may be either genetically determined or secondarily acquired. Various triggering events lead to autoimmunity with stimulation of the thyroid gland resulting in the clinical syndrome of hyperthyroidism. Also, relapse risk differs from patient to patient and can be estimated from clinical parameters incorporated into the Graves' Recurrent Events After Therapy (GREAT) score. Accurate risk stratification may help to distinguish high-risk patients for whom a more definitive treatment approach should be used from others where there is a high probability that the disease will recover with medical treatment alone. Several smaller trials having found positive effects of immunosuppressive drugs on recurrence risk in Graves' disease; therefoore, there is great potential in the use of novel immunomodulating drugs in addition to the currently used antithyroid drugs for the successful treatment of this condition. Further in-depth exploration of susceptibility, triggering factors and immunological mechanisms has the potential to improve treatment of Graves' disease, with more personalised, risk-adapted treatment strategies based on the different physiopathological concepts of this heterogeneous condition.

Toxicological considerations for antithyroid drugs in children.

PubMed

Karras, Spiros; Tzotzas, Themistoklis; Krassas, Gerasimos E

2011-04-01

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU). The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves’ disease

PubMed Central

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Abstract. Graves’ disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose. PMID:28203042

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves' disease.

PubMed

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Graves' disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose.

Comparison of curative effect of 131I and antithyroid drugs in Graves' disease: a meta analysis.

PubMed

Yuan, Ju; Lu, Xiuqing; Yue, Yan

2017-03-01

Radioactive 131I is currently reported to be a potential effective intervention for Graves' Disease treatment in China. Whether 131I treatment was associated with effective outcome or reduced risk of side effects, reccurence rate remained unknown. Eligible studies were selected from Chinese VIP, Wangfang, CNKI databases using the keywords "Iodine" and "Graves Disease". Finally, 13 clinical trials met the inclusion criterion and were included this meta-analysis. Our meta-analysis included 1355 patients diagnosed of Graves' Disease with regular anti-thyroid drugs oral administration and 1320 patients with 131I therapy. The results showed that there was significant symptom improvement with radioactive iodine intervention (Odd Ratio (OR)=4.50, 95% CI [3.55, 5.71], P<0.01). 3 studies mentioned side effects, 6 mentioned reccurence rate and another 6 mentioned hypothyroidism. The ORs and 95%CIs for these subgroups were 0.12 [0.06, 0.21], 0.08 [0.05, 0.13] and 2.27 [1.77, 2.92] respectively. It means a significant reduction of side effects and reccurence rate but increased hypothyroidism after 131I intervention in Graves' Disease. Treatment with 131I was associated with better clinical outcome; it reduced side effects and reccurence rate but increased hypothyroidism in Graves' Disease.

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.

Interventions for preventing and treating hyperthyroidism in pregnancy

PubMed Central

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2014-01-01

Background Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. Objectives To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010). Selection criteria We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Data collection and analysis Two review authors would have assessed trial eligibility and risk of bias, and extracted data. Main results No trials were located. Authors’ conclusions As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil. PMID:20824882

Rescue of Graves Thyrotoxicosis-Induced Cholestatic Liver Disease Without Antithyroid Drugs: A Case Report.

PubMed

Yan, Lily D; Thomas, Dylan; Schwartz, Michael; Reich, Jason; Steenkamp, Devin

2017-03-01

Graves thyrotoxicosis rarely presents with painless jaundice resulting from hyperthyroidism-associated hepatotoxicity, without preexisting liver disease. Management in patients with this presentation is challenging, given that the thionamides, methimazole and propylthiouracil, have both been associated with drug-induced liver injury. Radioactive iodine ablation and thyroidectomy are well-established alternatives, but each have their associated risks and contraindications. We present an unusual case of severe hyperthyroidism-associated hepatotoxicity, in which adjuvant therapies, including glucocorticoids, saturated solution of potassium iodide, and cholestyramine, were used as a bridge to definitive therapy with thyroidectomy.

Copper(II) complexes of methimazole, an anti Grave's disease drug. Synthesis, characterization and its potential biological behavior as alkaline phosphatase inhibitor.

PubMed

Urquiza, Nora M; Manca, Silvia G; Moyano, María A; Dellmans, Raquel Arrieta; Lezama, Luis; Rojo, Teófilo; Naso, Luciana G; Williams, Patricia A M; Ferrer, Evelina G

2010-04-01

Methimazole (MeimzH) is an anti-thyroid drug and the first choice for patients with Grave's disease. Two new copper(II) complexes of this drug: [Cu(MeimzH)(2)(NO(3))(2)]*0.5H(2)O and [Cu(MeimzH)(2)(H(2)O)(2)](NO(3))(2)*H(2)O were synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis and UV-vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is known that copper(II) cation can act as an inhibitor of alkaline phosphatase (ALP), the inhibitory effect of methimazole and its copper(II) complexes on ALP activity has also been investigated.

Hyperthyroidism Due to a Thyrotropin Secreting Pituitary Adenoma: Studies of Thyrotropin and Subunit Secretion

DTIC Science & Technology

1982-03-10

ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK Division of Medicine , Walter Reed Army Institute o7 AREA & WORK UNIT NUMBERS Research, Endocrine Metabolic...Service, Walter Reed C Army Medical Center, Washington, D.C. 20012 I. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Division of Medicine Walter...THIS PAGE (When Date Entered) * .1 Unclassified SECURITY CLASSIFICATION OF THIS PAGIE(When "ea Entmuod)- antithyroid drug therapy. Estrogens produced a

Potentiometric titration of thiols, cationic surfactants and halides using a solid-state silver-silver sulphide electrode.

PubMed

Pinzauti, S; Papeschi, G; La Porta, E

1983-01-01

A rugged, low resistance silver-silver sulphide solid-state electrode for determining pharmaceuticals as authentic samples or in dosage forms by potentiometric titration is described. Sodium tetraphenylborate, mercury(II) acetate and silver nitrate (0.01) M were employed as titrants in the analysis of cationic surfactants (cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and chlorhexidine salts), antithyroid drugs (methimazole and propylthiouracil) or sodium halides respectively.

Intrauterine diagnosis and management of fetal goiter: a case report.

PubMed

Koyuncu, Faik Mumtaz; Tamay, Aslı Goker; Bugday, Sultan

2010-01-01

Fetal goiter can be the result of maternal hyperthyroidism treated with antithyroid drugs. Polyhydramnios may be the presenting symptom and can be diagnosed prenatally by sonography. We report a case of fetal goiter diagnosed at 30 weeks of gestation and fetal hypothyroidism confirmed by cordocentesis. Intra-amniotic levothyroxine was administered. Onset of preterm labor could not be prevented. The risks and benefits of intrauterine treatment of fetal goitrous hypothyroidism are discussed.

[Prevention and multimodal therapy of hyperthyroidism].

PubMed

Palitzsch, K-D

2008-12-01

Subclinical and overt hyperthyroidism have been associated with various negative clinical outcomes as for example an increased risk of atrial fibrillation or increased cardiovascular mortality, especially in old age. In order to avoid hyperthyroidism it is strongly recommended not to start any iodine containing drug therapy or to avoid application of contrast agents unless the patient presents with an unremarkable clinical course. TSH suppressive therapy for the treatment of endemic goiter or differentiated low risk thyroid carcinoma is unnecessary, since it favours the development of subclinical hyperthyroidism. Overt hyperthyroidism is treated with antithyroid drugs and/or radioiodine therapy or surgery according to the underlying disease (toxic nodular goiter, Graves' disease).

Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features.

PubMed

Pariani, Nadia; Willis, Mark; Muller, Ilaria; Healy, Sarah; Nasser, Taha; McGowan, Anne; Lyons, Greta; Jones, Joanne; Chatterjee, Krishna; Dayan, Colin; Robertson, Neil; Coles, Alasdair; Moran, Carla

2018-06-06

Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves' disease (GD) with a reportedly indolent course. To determine the type, frequency and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated MS patients in the UK. Case records of alemtuzumab-treated patients who developed TD were reviewed. 41.1% (102/248; 80F, 22M) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2-107) following last dose; the majority (89%) within 3 years. Follow-up data (range 6-251 months) was available in 71 cases, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 GD patients commenced anti-thyroid drugs (ATD): 3 required radioiodine (RAI) due to ATD side-effects, drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI n=17, thyroidectomy n=5, long-term ATDs n=8). 3 cases of thyroiditis and 16 cases of hypothyroidism were documented; 5 with anti-TPO antibody positivity only, 10 with positive TRAb, 1 hypothyroidism (uncertain aetiology). Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Contrary to published literature, we have recorded frequent occurrence of GD that required definitive or prolonged antithyroid drug treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None.

PubMed

Laurberg, Peter; Andersen, Stine Linding

2015-11-01

Rare cases of birth defects after the use of methimazole (MMI) or carbimazole to treat hyperthyroidism in early pregnancy have been reported since 1972, whereas propylthiouracil (PTU) has not been considered teratogenic. Recently, two studies reported birth defects after the use of MMI in early pregnancy to affect 2-4% of exposed children, and one study also found birth defects after the use of PTU. On the other hand, some published studies did not find associations between the use of thionamides and birth defects. The methods used in the two positive and the four negative reports are reviewed. The two positive studies included a sufficient number of children exposed to MMI (n = 1231 and 1097) to evaluate the studied outcomes, whereas the four negative studies included a much lower number of exposed children (n = 73, 108, 30, and 124). Considering PTU, the birth defects observed in one study were in general milder and tended to be diagnosed and registered only when they resulted in complications and led to surgery after one year of age. None of the negative studies has investigated outcomes after one year of age. Studies finding no associations between early pregnancy exposure to antithyroid drugs and birth defects were either not sufficiently powered or did not study outcomes at optimal ages.

Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

PubMed

Moran, Carla; Habeb, Abdelhadi M; Kahaly, George J; Kampmann, Christoph; Hughes, Marina; Marek, Jan; Rajanayagam, Odelia; Kuczynski, Adam; Vargha-Khadem, Faraneh; Morsy, Mofeed; Offiah, Amaka C; Poole, Ken; Ward, Kate; Lyons, Greta; Halsall, David; Berman, Lol; Watson, Laura; Baguley, David; Mollon, John; Moore, Anthony T; Holder, Graham E; Dattani, Mehul; Chatterjee, Krishna

2017-09-01

Resistance to thyroid hormone β (RTH β ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTH β , with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTH β had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTH β in which life-threatening hyperthyroid features predominate.

The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of (131)I in Hyperthyroidism.

PubMed

Kartamihardja, A Hussein Sundawa; Massora, Stepanus

2016-01-01

The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended.

The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

PubMed Central

Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

2016-01-01

The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended. PMID:27134556

Trends in diagnostic and therapeutic criteria in Graves' disease in the last 10 years

PubMed Central

Escobar-Jimenez, F; Fernandez-Soto, M; Luna-Lopez, V; Quesada-Charneco, M; Glinoer, D

2000-01-01

A questionnaire describing a typical clinical case of Graves' disease and 10 variations on it was mailed to 70 Spanish units of endocrinology with the aim of assessing the new diagnostic and therapeutic trends for hyperthyroidism caused by Graves' disease in Spain and to compare the results obtained from previous studies carried out in Europe and Spain 10 years previously.
  Responses indicated that thyrotrophin (98%) and free thyroxine (88%) were the most used tests in the in vitro diagnosis of Graves' disease with a significant decrease in the use of total thyroxine, total triiodothyronine, and thyroglobulin in comparison with the surveys conducted 10 years previously in Europe and Spain. The presence of antibodies against the thyrotrophin receptor was the most frequently used immune marker in the diagnosis (78%) and the new use of antithyroperoxidase antibodies (36%) in diagnosis is noteworthy. Antithyroid drugs remain the treatment of choice (98%). Surgery was used mainly for large size goitres (33%) and radioiodine for recurrences after medical (61%) or surgical (80%) treatment.
  In conclusion, the responses obtained from this questionnaire provide insight into current specialist diagnostic and therapeutic practices with respect to Graves' disease and which could be of value to non-specialist units of endocrinology.


Keywords: Graves' disease; antithyroid drugs; radioiodine; surgery PMID:10824047

Study of factors that influence the outcome of 131I treatment in hyperthyroidism secondary to nodular goitre.

PubMed

Tabuenca-Dopico, O; Boente-Varela, R; Lamas-Ferreiro, J L

To assess the outcome after 131 I treatment in patients with multinodular (MNG) and nodular toxic goitre (NTG) according to the administered dose and other factors related to the patient, pathology, or previous treatments. A retrospective study was conducted on 108 patients (67 MNG and 41 NTG) treated in our department, with a follow-up period of at least 2 years. Development of hypothyroidism and treatment failure were evaluated along with their relationship with the administered dose and other factors such as age, sex, grade of hyperthyroidism, type of goitre, presence of autoimmunity, or previous antithyroid medication. More than one-third (36.9%) of MNG patients, and even higher proportion of NTG patients (51.2%) developed non-transient hypothyroidism, particularly in those receiving 740MBq (66.7%). No relationship was found with any other variable. The development of early hypothyroidism (before one year) was also not related to any variable. Treatment failure was not related to the dose, but in MNG there was a relationship with male gender, presence of autoimmunity, or previous antithyroid drugs use. The high rate of hypothyroidism obtained with high doses of 131 I in hyperthyroidism secondary to nodular goitre treatment suggests that lower doses might be sufficient to control the disease without an increase in treatment failures. Only patients with positive autoimmunity, in previous anti-thyroid medication, and perhaps male gender in MNG might be given higher doses, as the failure rate increases, but further studies are required. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Diagnosis and Management of Hyperthyroidism in Pregnancy: A Review.

PubMed

King, Jennifer Renae; Lachica, Ruben; Lee, Richard H; Montoro, Martin; Mestman, Jorge

2016-11-01

Hyperthyroidism has important implications for pregnancy, affecting both mother and fetus. Appropriate maternal and fetal management iscritical to avoiding adverse pregnancy outcomes and requires a multidisciplinary approach. To describe maternal diagnosis and management of hyperthyroidism, across all stages of pregnancy. In addition, to review clinical signs of fetal thyroid dysfunction due to maternal Graves disease and discuss management considerations. Review of published articles on PubMed and guidelines by recognized governing organizations regarding the diagnostic and management considerations for hyperthyroidism in pregnancy, from preconception to the postpartum period. Diagnosis of maternal hyperthyroidism involves both clinical symptoms and laboratory findings. Antithyroid medications are the mainstay of therapy, with trimester-specific pregnancy goals. Hyperthyroidism due to Graves disease has important diagnostic and management considerations for the fetus and neonate. Hyperthyroidism in pregnancy affects mother, fetus, and neonate. Interpretation of thyroid tests and understanding the appropriate use of antithyroid drugs are fundamental. Proper education of physicians providing care to women with hyperthyroidism is essential and starts before pregnancy. Postpartum follow-up is an essential part of the care. A systematic approach to management will ensure optimal pregnancy outcomes.

Sertraline and its iodine product: Experimental and theoretical vibrational studies. Potential in vitro anti-thyroid activity of sertraline and iodine product toxicity with respect to male Wistar rats

NASA Astrophysics Data System (ADS)

Escudero, Graciela E.; Ferraresi Curotto, Verónica; Laino, Carlos H.; Pis Diez, Reinaldo; Williams, Patricia A. M.; Ferrer, Evelina G.

2013-03-01

Mayor depression, obsessive-compulsive panic, social anxiety disorders are common diseases that are usually treated with sertraline hydrochloride which is the active ingredient of the well known drugs as Zoloft and Lustral. In this work, we presented a more complete vibrational characterization of the solid phase FT-IR spectra of Sertraline hydrochloride and its sertraline-iodine product in which the conformational space of the molecules was investigated performing molecular dynamic simulations within an NVT ensemble. Geometrical, electronic and vibrational properties were calculated with the density functional theory. Comparison of the simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes of both molecules. In addition, for the first time we present the evaluation of anti-thyroid activity of sertraline hydrochloride by using the Lang's method. Also, with the aim to evaluate the antidepressant effect of its iodine product we demonstrated for this compound the toxic effect towards the male Wistar rats.

Coexistence of adult-onset Still's disease and autoimmune hyperthyroidism in a patient who responded to corticosteroids and β-blocker.

PubMed

Chen, Hsiao-Shuang; Yu, Kuang-Hui; Ho, Huei-Huang

2010-12-01

The pathogenesis of adult-onset Still's disease (AOSD), which is currently thought to be an autoimmune disorder, may share similarities with autoimmune hyperthyroidism. This report describes a middle-aged woman in whom hyperthyroidism and Still's disease developed concurrently. During the course of her illness, the hyperthyroidism was observed to be aggravated whenever her AOSD was in the active stage. After her AOSD activity was controlled, her hyperthyroidism improved clinically. The extent of activation of her hyperthyroidism was observed in parallel to the extent of activation of her AOSD. Furthermore, the patient developed neutropenia after receiving either propylthiouracil (PTU) or methimazole, both of which are standard accepted medications for treatment of hyperthyroidism. Immune mechanisms contributed to PTU induced neutropenia have been proposed, and hyperthyroid patients treated with standard antithyroid agents should be monitored for blood cell counts especially for AOSD patients. Corticosteroid may effect Graves' disease activity, and steroids may play a role in the treatment of hyperthyroidism if a patient had drug allergies to antithyroid agents.

Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha-subunit and GH.

PubMed

Patrick, A W; Atkin, S L; MacKenzie, J; Foy, P M; White, M C; MacFarlane, I A

1994-02-01

A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.

[Rare side effects in management of hyperthyroidism. Case report].

PubMed

Sohár, Gábor; Kovács, Mónika; Györkös, Andrea; Gasztonyi, Beáta

2016-05-29

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Excessive iodine intake does not increase the recurrence rate of graves' disease after withdrawal of the antithyroid drug in an iodine-replete area.

PubMed

Park, Sun Mi; Cho, Yoon Young; Joung, Ji Young; Sohn, Seo Young; Kim, Sun Wook; Chung, Jae Hoon

2015-03-01

The relationship between iodine intake and effects of antithyroid drugs (ATD) for Graves' disease, especially in iodine-deficient areas, has been demonstrated in many studies. However, it was not clear how chronic high iodine intake influenced the effectiveness of ATD in an iodine-replete area. This study aimed to clarify the effect of iodine intake on clinical outcomes of Graves' disease after discontinuation of ATD in Korea, an iodine-replete area. A total of 142 patients with Graves' disease who visited the outpatient clinic regularly and stopped their ATD between October 2011 and April 2013 were enrolled in our study. Urinary iodine concentration (UIC) was measured just before and after the discontinuation of ATD. Median UIC was not significantly different between the remission and relapse groups, as well as among the four treatment groups (group 1, remission after initial treatment; group 2, remission after repeated treatment; group 3, early relapse within a year; group 4, late relapse after a year). Remission rates did not show a significant difference between the excessive iodine intake (UIC ≥300 μg/l) and average iodine intake groups (UIC <300 μg/l). The present study suggests that excessive iodine intake does not have an effect on the clinical outcomes of Graves' disease in an iodine-replete area, and therefore diet control with iodine restriction might not be necessary in the management of Graves' disease.

Excessive Iodine Intake Does Not Increase the Recurrence Rate of Graves' Disease after Withdrawal of the Antithyroid Drug in an Iodine-Replete Area

PubMed Central

Park, Sun Mi; Cho, Yoon Young; Joung, Ji Young; Sohn, Seo Young; Kim, Sun Wook; Chung, Jae Hoon

2015-01-01

Background and Objectives The relationship between iodine intake and effects of antithyroid drugs (ATD) for Graves' disease, especially in iodine-deficient areas, has been demonstrated in many studies. However, it was not clear how chronic high iodine intake influenced the effectiveness of ATD in an iodine-replete area. This study aimed to clarify the effect of iodine intake on clinical outcomes of Graves' disease after discontinuation of ATD in Korea, an iodine-replete area. Methods A total of 142 patients with Graves' disease who visited the outpatient clinic regularly and stopped their ATD between October 2011 and April 2013 were enrolled in our study. Urinary iodine concentration (UIC) was measured just before and after the discontinuation of ATD. Results Median UIC was not significantly different between the remission and relapse groups, as well as among the four treatment groups (group 1, remission after initial treatment; group 2, remission after repeated treatment; group 3, early relapse within a year; group 4, late relapse after a year). Remission rates did not show a significant difference between the excessive iodine intake (UIC ≥300 μg/l) and average iodine intake groups (UIC <300 μg/l). Conclusions The present study suggests that excessive iodine intake does not have an effect on the clinical outcomes of Graves' disease in an iodine-replete area, and therefore diet control with iodine restriction might not be necessary in the management of Graves' disease. PMID:25960960

Analysis of antithyroid drugs in surface water by using liquid chromatography-tandem mass spectrometry.

PubMed

Pérez-Fernández, Virginia; Marchese, Stefano; Gentili, Alessandra; García, María Ángeles; Curini, Roberta; Caretti, Fulvia; Perret, Daniela

2014-11-07

This paper describes development and validation of a new method for the simultaneous determination of six antithyroid drugs (ATDs) in surface waters by using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Target compounds include two ATD classes: thiouracil derivatives (thiouracil (TU), methyl-thiouracil (MTU), propyl-thiouracil (PTU), phenyl-thiouracil (PhTU)) and imidazole derivatives (tapazole (TAP), and mercaptobenzimidazole (MBI)). Sensitivity and selectivity of the LC-multiple reaction monitoring (MRM) analysis allowed applying a simple pre-concentration procedure and "shooting" the concentrated sample into the LC-MS/MS system without any other treatment. Recoveries were higher than 75% for all analytes. Intra-day precision and inter-day precision, calculated as relative standard deviation (RSD), were below 19 and 22%, respectively. Limits of detection (LODs) ranged from 0.05 to 0.25 μg/L; limits of quantitation (LOQs) varied between 0.15 and 0.75 μg/L. The validated method was successfully applied to the analysis of ATD residues in surface water samples collected from the Tiber River basin and three lakes of Lazio (central Italy). The analytes were quantified based on matrix-matched calibration curves with mercaptobenzimidazole-d4 (MBI-d4) as the internal standard (IS). The most widespread compound was TAP, one of the most common ATDs used in human medicine, but also TU and MBI were often detected in the analysed samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Congenital anomalies in children exposed to antithyroid drugs in-utero: a meta-analysis of cohort studies.

PubMed

Li, Huixia; Zheng, Jianfei; Luo, Jiayou; Zeng, Rong; Feng, Na; Zhu, Na; Feng, Qi

2015-01-01

Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero. Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests. Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively. The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis.

PubMed

Yang, Jing; Lv, Yuncheng; Zhang, Yi; Li, Jiaoyang; Chen, Yajun; Liu, Chang; Zhong, Jing; Xiao, Xinhua; Liu, Jianghua; Wen, Gebo

2018-01-01

We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis. In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. miR-17-92 expression levels in granulocytes of those six patients under the granulocytopenia condition were measured and compared with corresponding granulocyte samples after recovery. Additionally, the expression levels of these miRNAs in patients with type I or type II bone marrow characteristics were analyzed, and the correlation between miR-17-92 and serum free thyroxine level was analyzed. We found that levels of miR-17-92 expression decreased in both serum and pre-agranulocytosis granulocytes from patients with ATD-induced agranulocytosis compared with those in serum and granulocytes from both recovered patients and control patients. However, no difference among patients with either type of bone marrow characteristics was observed, and no correlation between serum miR-17-92 and free thyroxine levels was found. In ATD-induced agranulocytosis, expression of the miR-17-92 cluster is reduced in both serum and granulocytes, though this alteration does not correlate with bone marrow characteristics or thyroid function.

Congenital Anomalies in Children Exposed to Antithyroid Drugs In-Utero: A Meta-Analysis of Cohort Studies

PubMed Central

Luo, Jiayou; Zeng, Rong; Feng, Na; Zhu, Na; Feng, Qi

2015-01-01

Background Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero. Methods Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I 2 tests. Results Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively. Conclusions The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly. PMID:25974033

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication.

PubMed

Numbenjapon, N; Costin, G; Pitukcheewanont, P

2012-09-01

We assessed bone size and bone density (BD) measurements using computed tomography (CT) in children and adolescents with hyperthyroidism treated with antithyroid medication. We found that cortical BD appeared to improve at 1 year and normalize at 2 years in all tested patients. Our previous study demonstrated that cortical BD in children and adolescents with untreated hyperthyroidism was significantly decreased as compared to age-, sex- and ethnicity-matched healthy controls. The present report evaluated whether attainment of euthyroidism by medical antithyroid treatment was able to improve or normalize cortical BD in these patients. Anthropometrics and three-dimensional CT bone measurements including cross-sectional area (CSA), cortical bone area (CBA) and cortical BD at midshaft of the femur (cortical bone), and CSA and BD of L(1) to L(3) vertebrae (cancellous bone) in 15 children and adolescents after 1- and 2-year treatments with antithyroid medication were reviewed and compared to their pretreatment results. All patients were euthyroid at 1 and 2 years after medical antithyroid treatment. After adjusting for age, height, weight and Tanner stage, a significant increase in cortical BD in all patients (15/15) was found after 1 year of treatment (P < 0.001). Normalization of cortical BD was demonstrated in all tested patients (10/15) after 2 years. There were no significant changes in the other cancellous or cortical bone parameters. Cortical BD was improved at 1 year and normalized at 2 years in hyperthyroid patients rendered euthyroid with antithyroid medication.

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.

Outcome of very long-term treatment with antithyroid drugs in Graves' hyperthyroidism associated with Graves' orbitopathy.

PubMed

Elbers, Laura; Mourits, Maarten; Wiersinga, Wilmar

2011-03-01

It is still debated which treatment modality for Graves' hyperthyroidism (GH) is most appropriate when Graves' orbitopathy (GO) is present. The preference in our center has been always to continue antithyroid drugs for GH (as the block-and-replace [B-R] regimen) until all medical and/or surgical treatments for GO are concluded and the eye disease does not require any further therapy (except prescription of lubricants). This usually takes more than 2 years. The aim of this study was to evaluate the outcome of long-term B-R regimen for GH in GO patients by assessment (after discontinuation of B-R) of (a) the recurrence rate of GH and (b) the relapse rate of GO and its association with recurrent GH and/or (131)I therapy. A retrospective follow-up study was done among all patients referred to the Academic Medical Center in Amsterdam between 1995 and 2005 for GO. The inclusion criteria for the study were a history of GH and GO and a history of treatment for GH with a B-R regimen for more than 2 years. The exclusion criteria were a history of (131)I therapy or thyroidectomy before the end of GO treatment. A questionnaire was sent to 255 patients and returned by 114. Of these patients, 73 qualified for the study. Recurrences of GH and/or GO as indicated by returned questionnaires were checked with treating physicians. Patients were treated with B-R for a median of 41 months (range: 24-132). The median follow-up after discontinuation of the B-R regimen was 57 months (range: 12-170). Recurrent GH occurred in 27 of the 73 study patients (37%) at a median of 3 months (range: 1-65) after withdrawal of antithyroid drug therapy. Nineteen of the 27 patients with recurrent hyperthyroidism were treated with (131)I therapy. A relapse of GO was not encountered in any of the 73 patients. The study suggests that long-term B-R treatment of GH in GO patients is associated with a recurrence rate of hyperthyroidism of about 37%. With the regimen employed, recurrence of hyperthyroidism and recurrence of hyperthyroidism followed by treatment with (131)I appears not to be a likely cause of relapse of GO. The data suggest that B-R treatment of GH until GO has become inactive and does not require any further treatment is a feasible option and does not jeopardize the improvement that occurred in GO.

Hashimoto thyroiditis, anti-thyroid antibodies and systemic lupus erythematosus.

PubMed

Posselt, Rayana T; Coelho, Vinícius N; Skare, Thelma L

2018-01-01

To study the prevalence of Hashimoto thyroiditis (HT), anti-thyroid autoantibodies (anti-thyroglobulin or TgAb and thyroperoxidase or TPOAb) in systemic lupus erythematosus (SLE) patients. To analyze if associated HT, TgAb and/or TPOAb influence clinical or serological profiles, disease activity and/or its cumulative damage. Three hundred and one SLE patients and 141 controls were studied for thyroid stimulating hormone, thyroxin, TgAb and TPOAb by chemiluminescence and immunometric assays. Patients' charts were reviewed for serological and clinical profiles. Activity was measured by SLE Disease Activity Index and cumulative damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. SLE patients were divided into: (i) with HT; (ii) with anti-thyroid antibodies but without HT; and (iii) without HT and without anti-thyroid antibodies, and were then compared. Furthermore, SLE patients were compared according to the number of positive anti-thyroid antibodies. Hashimoto thyroiditis prevalence in SLE was 12.6% and 5.6% in controls (P = 0.02; odds ratio = 2.4; 95% CI = 1.09-5.2). Lupus patients with HT had less malar rash (P = 0.02) and more anti-Sm (P = 0.04). Anti-Sm was more common in those with two anti-thyroid antibodies than in those with one or negative. The presence of HT or the number of positive autoantibodies did not associate either with disease activity (P = 0.95) or with cumulative damage (P = 0.98). There is a two-fold increased risk of HT in SLE patients. Anti-Sm antibodies favor this association and also double antibody positivity. Disease activity and cumulative damage are not related to HT or with autoantibodies. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Effects of drugs on the efficacy of radioiodine (|) therapy in hyperthyroid patients.

PubMed

Oszukowska, Lidia; Knapska-Kucharska, Małgorzata; Lewiński, Andrzej

2010-03-01

The treatment of hyperthyroidism is targeted at reducing the production of thyroid hormones by inhibiting their synthesis or suppressing their release, as well as by controlling their influence on peripheral tissue (conservative therapy, medical treatment). Radical treatment includes surgical intervention to reduce the volume of thyroid tissue or damage of the mechanisms of thyroid hormone synthesis by radioiodine ((131)|) administration. Radioiodine ((131)|) is a reactor radionuclide, produced as a result of uranium decomposition and emission of β and γ radiation. The therapeutic effects of the isotope are obtained by the emission of β radiation. In the paper, the effects of administered drugs (antithyroid, glucocorticosteroids, lithium carbonate, inorganic iodine, β-blockers) on the final outcome of radioiodine therapy in patients with hyperthyroidism are discussed.

Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge.

PubMed

Bhuyan, Ashok Krishna; Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

2014-01-01

Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations.

Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge

PubMed Central

Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

2014-01-01

Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations. PMID:25317178

Antithyroid medications and psychosis.

PubMed

Vita, Roberto; Mazzi, Valeria; Antonelli, Alessandro; Benvenga, Salvatore

2013-11-01

Antithyroid drugs (ATDs) are used in the treatment of hyperthyroidism. Very rarely ATDs were reported to trigger acute psychosis in patients with no history of psychiatric disturbances. Our aim is to review the literature on psychosis as a side effect of ATD and to give a personal opinion on this issue. The cases of acute psychosis elicited by ATD are few and most were reported many years ago, before radioimmunoassay for thyroid-stimulating hormone (TSH) and thyroid hormones was introduced. Most of those cases lack a description of serum thyroid hormone profile before, during and after the appearance of the psychiatric disorder; hence, an abrupt shift from hyperthyroidism to euthyroidism or hypothyroidism cannot be excluded. In addition, patients underwent specific psychiatric therapy, so that it is difficult to attribute the disappearance of the mental disorders to the withdrawal of ATD per se. Patients who develop mental disorders while under ATD should be followed by an accurate evaluation of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels throughout the course of the psychiatric disease. The use of new imaging techniques could be helpful in ruling out the encephalopathy associated with autoimmune thyroid diseases and other cerebral pathologies that might be possible causes of these mental disorders.

Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2

PubMed Central

Yanagawa, Yoshimaro; Aoki, Tomoyuki; Morimura, Tadashi; Araki, Osamu; Kimura, Takao; Ogiwara, Takayuki; Kotajima, Nobuo; Yanagawa, Masumi; Murakami, Masami

2014-01-01

In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population. PMID:24895636

Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A Nationwide Population-Based Cohort Study.

PubMed

Kwon, Hyemi; Jung, Jin Hyung; Han, Kyung Do; Park, Yong Gyu; Cho, Jung Hwan; Lee, Da Young; Han, Ji Min; Park, Se Eun; Rhee, Eun Jung; Lee, Won Young

2018-06-01

The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans. In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer. The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased. This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment. Copyright © 2018 Korean Endocrine Society.

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

PubMed Central

Nakamura, Hirotoshi; Ide, Akane; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Miyauchi, Akira

2016-01-01

Objective Finding agranulocytosis (AG) at an early stage is important to improve outcome, but periodic granulocyte count monitoring is not generally recommended for patients with Graves' disease, because AG develops suddenly. Method At the Kuma Hospital, Graves' patients under antithyroid drug (ATD) treatment in an outpatient clinic have a granulocyte count examination during each visit, and if it is <1,000/μl, a warning is immediately sent to the patient's physician. We evaluated the usefulness of this system. Results We investigated 25 AG and 33 granulocytopenia (GP) cases over a recent 5-year period, excluding patients who developed AG or GP at another hospital and were referred to us for treatment. Among the 25 AG patients, 16 patients (64%; 9 asymptomatic and 7 very mild symptomatic cases) were discovered by the periodic granulocyte count examination at an outpatient clinic. The remaining 9 patients visited the Kuma Hospital or other hospitals because of infection symptoms. Most of the AG patients were given granulocyte colony-stimulating factor injections immediately and were admitted if a prompt increase in granulocytes could not be obtained. The final treatments for Graves' disease were 131I-radioisotope therapy (19 patients), thyroidectomy (2 patients), inorganic iodine (1 patient), or another ATD (1 patient). Among the 33 GP patients, 31 (94%), including 20 asymptomatic cases, were discovered during periodic granulocyte count monitoring. Most of them stopped ATD, and other treatments for Graves' disease were selected. Conclusion Periodic monitoring of granulocyte counts is useful for identifying AG and GP patients with no or minimum infection symptoms. PMID:28101490

Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea.

PubMed

Kim, Hee Kyung; Yoon, Jee Hee; Jeon, Min Ji; Kim, Tae Yong; Shong, Young Kee; Lee, Min Jin; Kim, Bo Hyun; Kim, In Joo; Joung, Ji Young; Kim, Sun Wook; Chung, Jae Hoon; Kang, Ho Cheol

2015-12-01

Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients. We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm³. The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization. The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.

Graves' disease in children: long-term outcomes of medical therapy.

PubMed

Rabon, Shona; Burton, Amy M; White, Perrin C

2016-10-01

Management options are limited for the treatment of Graves' disease, and there is controversy regarding optimal treatment. We describe the demographic and biochemical characteristics of children with Graves' disease and the outcomes of its management. This is a retrospective study reviewing medical records from 2001 to 2011 at a tertiary-care paediatric hospital. Diagnostic criteria included elevated free T4 and total T3, suppressed TSH, and either positive thyroid-stimulating immunoglobulin or thyroid receptor antibodies or clinical signs suggestive of Graves' disease, for example exophthalmos. Patients were treated with antithyroid drugs (ATD), radioactive iodine, or thyroidectomy. The main outcome measures were remission after medical therapy for at least 6 months and subsequent relapse. A total of 291 children met diagnostic criteria. A total of 62 were male (21%); 117 (40%) were Hispanic, 90 (31%) Caucasian, and 59 (20%) African American. Mean age (±standard deviation) at diagnosis was 12·3 ± 3·8 (range 3-18·5) years. At diagnosis, 268 patients were started on an antithyroid drug and 23 underwent thyroid ablation or thyroidectomy. Fifty-seven (21%) children achieved remission and 16 (28%) of these patients relapsed, almost all within 16 months. Gender and ethnicity did not affect rates of remission or relapse. Of 251 patients treated with methimazole, 53 (21%) had an adverse reaction, including rash, arthralgias, elevated transaminases, or neutropenia. Most children with Graves' disease treated with ATD do not experience remission, but most remissions do not end in relapse. Adverse reactions to methimazole are common but generally mild. © 2016 John Wiley & Sons Ltd.

Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease.

PubMed

Nakamura, Hirotoshi; Ide, Akane; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Miyauchi, Akira

2016-12-01

Finding agranulocytosis (AG) at an early stage is important to improve outcome, but periodic granulocyte count monitoring is not generally recommended for patients with Graves' disease, because AG develops suddenly. At the Kuma Hospital, Graves' patients under antithyroid drug (ATD) treatment in an outpatient clinic have a granulocyte count examination during each visit, and if it is <1,000/μl, a warning is immediately sent to the patient's physician. We evaluated the usefulness of this system. We investigated 25 AG and 33 granulocytopenia (GP) cases over a recent 5-year period, excluding patients who developed AG or GP at another hospital and were referred to us for treatment. Among the 25 AG patients, 16 patients (64%; 9 asymptomatic and 7 very mild symptomatic cases) were discovered by the periodic granulocyte count examination at an outpatient clinic. The remaining 9 patients visited the Kuma Hospital or other hospitals because of infection symptoms. Most of the AG patients were given granulocyte colony-stimulating factor injections immediately and were admitted if a prompt increase in granulocytes could not be obtained. The final treatments for Graves' disease were 131 I-radioisotope therapy (19 patients), thyroidectomy (2 patients), inorganic iodine (1 patient), or another ATD (1 patient). Among the 33 GP patients, 31 (94%), including 20 asymptomatic cases, were discovered during periodic granulocyte count monitoring. Most of them stopped ATD, and other treatments for Graves' disease were selected. Periodic monitoring of granulocyte counts is useful for identifying AG and GP patients with no or minimum infection symptoms.

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.

Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.

PubMed

Kempers, Marlies J E; van Tijn, David A; van Trotsenburg, A S Paul; de Vijlder, Jan J M; Wiedijk, Brenda M; Vulsma, Thomas

2003-12-01

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T(4) supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves' disease is preserving euthyroidism throughout pregnancy.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy.

PubMed

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-07-01

Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

PubMed Central

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-01-01

Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test. Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology. The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. PMID:26131823

Management of hyperthyroidism due to Graves' disease: frequently asked questions and answers (if any).

PubMed

Bartalena, L; Chiovato, L; Vitti, P

2016-10-01

Graves' disease is the most common cause of hyperthyroidism in iodine-replete areas. Although progress has been made in our understanding of the pathogenesis of the disease, no treatment targeting pathogenic mechanisms of the disease is presently available. Therapies for Graves' hyperthyroidism are largely imperfect because they are bound to either a high rate of relapsing hyperthyroidism (antithyroid drugs) or lifelong hypothyroidism (radioiodine treatment or thyroidectomy). Aim of the present article is to offer a practical guidance to the reader by providing evidence-based answers to frequently asked questions in clinical practice.

The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment.

PubMed

Fukao, Atsushi; Takamatsu, Junta; Kubota, Sumihisa; Miyauchi, Akira; Hanafusa, Toshiaki

2011-08-09

We previously reported that depressive personality (the scores of hypochondriasis, depression and psychasthenia determined by the Minnesota Multiphasic Personality Inventory (MMPI)) and daily hassles of Graves' disease (GD) patients treated long trem with antithyroid drug (ATD) were significantly higher in a relapsed group than in a remitted group, even in the euthyroid state. The present study aims to examine the relationship among depressive personality, emotional stresses, thyroid function and the prognosis of hyperthyroidism in newly diagnosed GD patients. Sixty-four untreated GD patients responded to the MMPI for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses before and during ATD treatment. In the untreated thyrotoxic state, depressive personality (T-scores of hypochondriasis, depression or psychasthenia greater than 60 points in MMPI) were found for 44 patients (69%). For 15 (23%) of these patients, the scores decreased to the normal range after treatment. However, depressive personality persisted after treatment in the remaining 29 patients (46%). Normal scores before treatment were found for 20 patients (31%), and the scores were persistently normal for 15 patients (23%). The remaining 5 patients (8%) had higher depressive personality after treatment. Such depressive personality was not associated with the severity of hyperthyroidism. Serum TSH receptor antibody activity at three years after treatment was significantly (p = 0.0351) greater in the depression group than in the non- depression group. The remission rate at four years after treatment was significantly (p = 0.0305) lower in the depression group than in the non- depression group (22% vs 52%). The data indicate that in GD patients treated with ATD, depressive personality during treatment reflects the effect of emotional stress more than that of thyrotoxicosis and that it aggravates hyperthyroidism. Psychosomatic therapeutic approaches including antipsychiatric drugs and/or psychotherapy appears to be useful for improving the prognosis of hyperthyroidism.

Antithyroid Drugs and Congenital Malformations: A Nationwide Korean Cohort Study.

PubMed

Seo, Gi Hyeon; Kim, Tae Hyuk; Chung, Jae Hoon

2018-03-20

Untreated or insufficiently treated Graves disease in pregnancy may pose risks to both mother and fetus. Antithyroid drugs (ATDs) are the treatment mainstay, but the potential teratogenic effect of these drugs has prompted clinicians to question the safe management of this vulnerable population. To examine the association between maternal prescriptions for ATDs and congenital malformations in live births. Nationwide cohort study. Korean National Health Insurance database. A cohort of 2 886 970 completed pregnancies linked to live-born infants in 2 210 253 women between 2008 and 2014. Maternal prescriptions for ATDs in the first trimester. The risk for overall and organ-specific congenital malformations in offspring, with logistic regression models used to control for potential confounders. 12 891 pregnancies (0.45%) were exposed to ATDs during the first trimester. The prevalence of malformations in exposed offspring was 7.27%, compared with 5.94% in offspring of women who were not prescribed ATDs during pregnancy (P < 0.001) (adjusted odds ratio, 1.19 [95% CI, 1.12 to 1.28]). Absolute increases in the prevalence of congenital malformations per 1000 live births were 8.81 cases (CI, 3.92 to 13.70 cases) for propylthiouracil alone, 17.05 cases (CI, 1.94 to 32.15 cases) for methimazole (MMI) alone, and 16.53 cases (CI, 4.73 to 28.32 cases) for propylthiouracil and MMI, compared with pregnancies without ATD prescriptions. In the MMI group, a high cumulative dose (>495 mg) during the first trimester was associated with an increased risk for malformations compared with a low dose (1 to 126 mg) (adjusted odds ratio, 1.87 [CI, 1.06 to 3.30]). The study used a prescription claims database to assess ATD exposure. Exposure to ATDs during the first trimester was associated with increased risk for congenital malformations, particularly for pregnancies in which women received prescriptions for MMI or both ATDs. None.

The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

PubMed Central

2011-01-01

Background We previously reported that depressive personality (the scores of hypochondriasis, depression and psychasthenia determined by the Minnesota Multiphasic Personality Inventory (MMPI)) and daily hassles of Graves' disease (GD) patients treated long trem with antithyroid drug (ATD) were significantly higher in a relapsed group than in a remitted group, even in the euthyroid state. The present study aims to examine the relationship among depressive personality, emotional stresses, thyroid function and the prognosis of hyperthyroidism in newly diagnosed GD patients. Methods Sixty-four untreated GD patients responded to the MMPI for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses before and during ATD treatment. Results In the untreated thyrotoxic state, depressive personality (T-scores of hypochondriasis, depression or psychasthenia greater than 60 points in MMPI) were found for 44 patients (69%). For 15 (23%) of these patients, the scores decreased to the normal range after treatment. However, depressive personality persisted after treatment in the remaining 29 patients (46%). Normal scores before treatment were found for 20 patients (31%), and the scores were persistently normal for 15 patients (23%). The remaining 5 patients (8%) had higher depressive personality after treatment. Such depressive personality was not associated with the severity of hyperthyroidism. Serum TSH receptor antibody activity at three years after treatment was significantly (p = 0.0351) greater in the depression group than in the non- depression group. The remission rate at four years after treatment was significantly (p = 0.0305) lower in the depression group than in the non- depression group (22% vs 52%). Conclusion The data indicate that in GD patients treated with ATD, depressive personality during treatment reflects the effect of emotional stress more than that of thyrotoxicosis and that it aggravates hyperthyroidism. Psychosomatic therapeutic approaches including antipsychiatric drugs and/or psychotherapy appears to be useful for improving the prognosis of hyperthyroidism. PMID:21827669

Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center.

PubMed

He, Y; Li, J; Zheng, J; Khan, Z; Qiang, W; Gao, F; Zhao, Y; Shi, B

2017-07-01

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening adverse drug reaction that occurs in patients during the treatment of Graves' disease. We aimed to comprehensively examine data for patients with this rare complication and to improve the clinical safety of ATDs. We retrospectively reviewed the medical records of 64 hospitalized patients diagnosed with ATD-induced agranulocytosis between 2000 and 2015. Agranulocytosis occurred in 52 (81.3%) patients within the first 3 months after initiation of ATD therapy. Fever (84.4%) and sore throat (82.8%) were the most common symptoms. Although they experienced symptoms, 30 (46.9%) patients did not seek treatment immediately and delayed their diagnosis of agranulocytosis. The minimum granulocyte count was lower in the patients diagnosed after the appearance of symptoms than in those diagnosed before the appearance of symptoms (0.01 × 10 9 /L (0 × 10 9 /L - 0.06 × 10 9 /L) versus 0.26 × 10 9 /L (0.05 × 10 9 /L - 0.40 × 10 9 /L), P < 0.001). The interval days from the appearance of symptoms to the diagnosis of agranulocytosis were negatively correlated with the minimum granulocyte count (r = -0.348, P = 0.005). In addition, a lower minimum granulocyte count was associated with a longer recovery time (β = -11.899, 95% CI -15.304 to -8.496). Our findings have demonstrated that delayed diagnosis of ATD-induced agranulocytosis is common in our population. Delayed diagnosis is associated with severe agranulocytosis and may prolong the recovery time from agranulocytosis. Monitoring of the white blood cell and granulocyte counts may be an effective way to establish an early diagnosis and prevent progression to severe agranulocytosis.

Follow-up and evaluation of the pregnancy outcome in women of reproductive age with Graves' disease after 131Iodine treatment.

PubMed

Zhang, Li-Hua; Li, Jing-Yan; Tian, Qi; Liu, Shuang; Zhang, Hong; Liu, Sheng; Liang, Jiu-Gen; Lu, Xian-Ping; Jiang, Ning-Yi

2016-11-01

The aims of the present study were to analyze the outcomes of pregnancy, after 131 I treatment, in patients of reproductive age with Graves' hyperthyroidism and to investigate the effects, if any, of the 131 I treatment on the mothers and newborns. From 2009 to 2014, 257 pregnant female patients with Graves' hyperthyroidism in the outpatients at the Department of Nuclear Medicine and 166 healthy pregnant women from the Department of Obstetrics at Sun Yat-Sen Memorial Hospital were included in our study. They were divided into a 131 I therapy group (n = 130) and an anti-thyroid drug (ATD) group (n = 127) according to their therapy before conception. The neonatal gender, rate of preterm birth, body weight ratio and occurrence of low birth weight [except for higher rates of abortion (odds ratio; OR = 2.023) and cesarean delivery (OR = 1.552) in patients with Graves' hyperthyroidism] showed no statistically significant differences from those of the healthy group (P > 0.05). The level of intrauterine growth restriction did not differ between the Graves' hyperthyroidism group and the healthy group (8 vs 2, 3.0% vs 1.2%). The outcomes of pregnancy among the 131 I therapy group, ATD group and healthy group also showed no significant differences. Of the patients treated with 131 I, no significant differences were observed in the outcomes of their pregnancies, whether they received propylthiouracil (PTU), levothyroxine or no additional drug treatment during pregnancy. Women with hyperthyroidism who were treated with 131 I therapy could have normal delivery if they ceased 131 I treatment for at least six months prior to conception and if their thyroid function was reasonably controlled and maintained using the medication: anti-thyroid drug and levothyroxine before and during pregnancy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Follow-up and evaluation of the pregnancy outcome in women of reproductive age with Graves’ disease after 131Iodine treatment

PubMed Central

Zhang, Li-Hua; Li, Jing-Yan; Tian, Qi; Liu, Shuang; Zhang, Hong; Liu, Sheng; Liang, Jiu-Gen; Lu, Xian-Ping; Jiang, Ning-Yi

2016-01-01

The aims of the present study were to analyze the outcomes of pregnancy, after 131I treatment, in patients of reproductive age with Graves’ hyperthyroidism and to investigate the effects, if any, of the 131I treatment on the mothers and newborns. From 2009 to 2014, 257 pregnant female patients with Graves’ hyperthyroidism in the outpatients at the Department of Nuclear Medicine and 166 healthy pregnant women from the Department of Obstetrics at Sun Yat-Sen Memorial Hospital were included in our study. They were divided into a 131I therapy group (n = 130) and an anti-thyroid drug (ATD) group (n = 127) according to their therapy before conception. The neonatal gender, rate of preterm birth, body weight ratio and occurrence of low birth weight [except for higher rates of abortion (odds ratio; OR = 2.023) and cesarean delivery (OR = 1.552) in patients with Graves’ hyperthyroidism] showed no statistically significant differences from those of the healthy group (P > 0.05). The level of intrauterine growth restriction did not differ between the Graves’ hyperthyroidism group and the healthy group (8 vs 2, 3.0% vs 1.2%). The outcomes of pregnancy among the 131I therapy group, ATD group and healthy group also showed no significant differences. Of the patients treated with 131I, no significant differences were observed in the outcomes of their pregnancies, whether they received propylthiouracil (PTU), levothyroxine or no additional drug treatment during pregnancy. Women with hyperthyroidism who were treated with 131I therapy could have normal delivery if they ceased 131I treatment for at least six months prior to conception and if their thyroid function was reasonably controlled and maintained using the medication: anti-thyroid drug and levothyroxine before and during pregnancy. PMID:27618833

Spectroscopic and structural investigation of interaction of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt with molecular iodine

NASA Astrophysics Data System (ADS)

Ivolgina, Victoria A.; Chernov'yants, Margarita S.

2018-06-01

The interest in the study of heteroaromatic thioamides which are known to exhibit antithyroid activity is stimulated by the variety and an unusual structure their complexes with molecular iodine. The directions of dithiones investigation are diversity enough, however a few works are devoted to the study them as the potential thyreostatics. The ability of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thion potassium salt to form the outer-sphere charge-transfer complex in dilute chloroform solution, coordinating 2 iodine molecules has been studied by UV-vis spectroscopy (lgβ = 7.91). The compound of the 5,5‧-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) - product of irreversible oxidation of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt has been isolated and characterized by X-ray diffraction. Intermolecular interactions between sulfur atoms are observed with very short interatomic distance, shorter than sum of van der Waals radii. The contact between heterocyclic sulfur and heterocyclic nitrogen is also slightly short - 3.169 Å (0.053 Å less than vdW radii sum). This investigation constitutes a starting point for study of novel antithyroid drugs in future.

Spectroscopic and structural investigation of interaction of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt with molecular iodine.

PubMed

Ivolgina, Victoria A; Chernov'yants, Margarita S

2018-06-15

The interest in the study of heteroaromatic thioamides which are known to exhibit antithyroid activity is stimulated by the variety and an unusual structure their complexes with molecular iodine. The directions of dithiones investigation are diversity enough, however a few works are devoted to the study them as the potential thyreostatics. The ability of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thion potassium salt to form the outer-sphere charge-transfer complex in dilute chloroform solution, coordinating 2 iodine molecules has been studied by UV-vis spectroscopy (lgβ=7.91). The compound of the 5,5'-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) - product of irreversible oxidation of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt has been isolated and characterized by X-ray diffraction. Intermolecular interactions between sulfur atoms are observed with very short interatomic distance, shorter than sum of van der Waals radii. The contact between heterocyclic sulfur and heterocyclic nitrogen is also slightly short - 3.169Å (0.053Å less than vdW radii sum). This investigation constitutes a starting point for study of novel antithyroid drugs in future. Copyright © 2018 Elsevier B.V. All rights reserved.

Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

PubMed Central

Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

Background For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse. PMID:24783027

Genotype and phenotype predictors of relapse of graves' disease after antithyroid drug withdrawal.

PubMed

Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

For patients with Graves' disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. FOUR SNPS WERE SIGNIFICANTLY ASSOCIATED WITH DISEASE RELAPSE: rs231775 (OR 1.96, 95% CI 1.18-3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01-62.7), rs11569309 (OR 8.09, 95% CI 1.03-63.7), and rs3765457 (OR 2.60, 95% CI 1.08-6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09-1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05-1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15-2.35), and smoking habit (HR 1.60, 95% CI 1.05-2.42). Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.

Quality of life aspects and costs in treatment of Graves' hyperthyroidism with antithyroid drugs, surgery, or radioiodine: results from a prospective, randomized study.

PubMed

Ljunggren, J G; Törring, O; Wallin, G; Taube, A; Tallstedt, L; Hamberger, B; Lundell, G

1998-08-01

The patients' views and costs of three different forms of treatment for Graves' hyperthyroidism were investigated. The study comprises 174 patients with Graves' hyperthyroidism who were stratified into two age groups: 20 to 34 years and 35 to 55 years. The younger group was randomly assigned to treatment with antithyroid drug plus thyroxine for 18 months or subtotal thyroidectomy, and in the older group iodine-131 was added as a third alternative. The patients' views of their therapy were based on a questionnaire formulated to identify possible differences between the three treatment forms. The costs were assessed by analyzing the official hospital reimbursement system for both outpatient and inpatient costs for a period of 2 years from the day of randomization. The results show that no significant differences in opinion were found between the five treatment groups with regard to any of the questions. Furthermore, only 10% of the patients expressed slight and 3% major hesitation to recommend the treatment form received to a friend with similar disease. Twenty percent of the patients with endocrine ophthalmopathy reported the eye problems to be much more troublesome and 14% somewhat more troublesome than the thyroid problems. The cost proportion between the medical and surgical treatment in the young group was 1:2.5 (1 = 1126 United States dollars [USD]) before and 1:1.3 (1 = 2284 USD) after inclusion of the relapse costs. The proportion between the medical, surgical, and iodine-131 treatment in the older group was 1:2.5:1.6 (1 = 1164 USD) before and 1:1.6:1.4 (1 = 1972 USD) after inclusion of the relapse costs.

Methodological Quality Assessment of Meta-Analyses of Hyperthyroidism Treatment.

PubMed

Qin, Yahong; Yao, Liang; Shao, Feifei; Yang, Kehu; Tian, Limin

2018-01-01

Hyperthyroidism is a common condition that is associated with increased morbidity and mortality. A number of meta-analyses (MAs) have assessed the therapeutic measures for hyperthyroidism, including antithyroid drugs, surgery, and radioiodine, however, the methodological quality has not been evaluated. This study evaluated the methodological quality and summarized the evidence obtained from MAs of hyperthyroidism treatments for radioiodine, antithyroid drugs, and surgery. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database databases. Two investigators independently assessed the meta-analyses titles and abstracts for inclusion. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. A total of 26 MAs fulfilled the inclusion criteria. Based on the AMSTAR scores, the average methodological quality was 8.31, with large variability ranging from 4 to 11. The methodological quality of English meta-analyses was better than that of Chinese meta-analyses. Cochrane reviews had better methodological quality than non-Cochrane reviews due to better study selection and data extraction, the inclusion of unpublished studies, and better reporting of study characteristics. The authors did not report conflicts of interest in 53.8% meta-analyses, and 19.2% did not report the harmful effects of treatment. Publication bias was not assessed in 38.5% of meta-analyses, and 19.2% did not report the follow-up time. Large-scale assessment of methodological quality of meta-analyses of hyperthyroidism treatment highlighted methodological strengths and weaknesses. Consideration of scientific quality when formulating conclusions should be made explicit. Future meta-analyses should improve on reporting conflict of interest. © Georg Thieme Verlag KG Stuttgart · New York.

Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea

PubMed Central

Kim, Hee Kyung; Yoon, Jee Hee; Jeon, Min Ji; Kim, Tae Yong; Shong, Young Kee; Lee, Min Jin; Kim, Bo Hyun; Kim, In Joo; Joung, Ji Young; Kim, Sun Wook; Chung, Jae Hoon

2015-01-01

Background Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients. Methods We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm3. Results The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization. Conclusion The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease. PMID:26394729

Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

PubMed Central

2010-01-01

Context Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003). Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones. PMID:20807449

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

PubMed

Kwon, Hyemi; Kim, Won Gu; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin Sook; Shong, Young Kee; Kim, Won Bae

2016-06-01

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

PubMed Central

Kwon, Hyemi; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin-Sook; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. Methods This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Results Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. Conclusion TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease. PMID:27118279

Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves' disease.

PubMed

Inukai, Yoshihisa; Momobayashi, Atsushi; Sugawara, Naoto; Aso, Yoshimasa

2007-06-01

Although Graves' disease is considered an autoantibody-mediated, T-helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase. We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients with Graves' disease after treatment of methimazole (MMI), an antithyroid drug. University clinic outpatients were studied prospectively. Subjects included 23 untreated hyperthyroid patients with Graves' disease and 17 age-matched control subjects. Before and after treatment, we measured Th1- and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood lymphocytes using flow cytometry, as well as plasma concentrations of their ligands, interferon-inducible protein (IP)-10 and thymus and activation-regulated chemokine (TARC). The percentage of CXCR3-expressing cells among CD4+T lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves' disease patients than in controls. At 12 and 24 weeks after initiation of MMI, percentage of CXCR3-expressing CD4+T lymphocytes had decreased significantly, while the percentage of CCR4-expressing CD4+T lymphocytes had increased significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24 weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24 weeks. Plasma concentrations of TARC also had decreased significantly at 24 weeks. In hyperthyroid patients with Graves' disease in the active phase, Th1 cells rather than Th2 cells predominated among peripheral blood lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2 dominance occurred.

Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study

PubMed Central

Wang, Meng-Ting; Lee, Wan-Ju; Huang, Tien-Yu; Chu, Che-Li; Hsieh, Chang-Hsun

2014-01-01

Aims The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner. Methods We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively. Results The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22). Conclusions MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis. PMID:25279406

Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves' disease.

PubMed

Donovan, Peter J; McLeod, Donald S A; Little, Richard; Gordon, Louisa

2016-12-01

Little data is in existence about the most cost-effective primary treatment for Graves' disease. We performed a cost-utility analysis comparing radioactive iodine (RAI), anti-thyroid drugs (ATD) and total thyroidectomy (TT) as first-line therapy for Graves' disease in England and Australia. We used a Markov model to compare lifetime costs and benefits (quality-adjusted life-years (QALYs)). The model included efficacy, rates of relapse and major complications associated with each treatment, and alternative second-line therapies. Model parameters were obtained from published literature. One-way sensitivity analyses were conducted. Costs were presented in 2015£ or Australian Dollars (AUD). RAI was the least expensive therapy in both England (£5425; QALYs 34.73) and Australia (AUD5601; 30.97 QALYs). In base case results, in both countries, ATD was a cost-effective alternative to RAI (£16 866; 35.17 QALYs; incremental cost-effectiveness ratio (ICER) £26 279 per QALY gained England; AUD8924; 31.37 QALYs; ICER AUD9687 per QALY gained Australia), while RAI dominated TT (£7115; QALYs 33.93 England; AUD15 668; 30.25 QALYs Australia). In sensitivity analysis, base case results were stable to changes in most cost, transition probabilities and health-relative quality-of-life (HRQoL) weights; however, in England, the results were sensitive to changes in the HRQoL weights of hypothyroidism and euthyroidism on ATD. In this analysis, RAI is the least expensive choice for first-line treatment strategy for Graves' disease. In England and Australia, ATD is likely to be a cost-effective alternative, while TT is unlikely to be cost-effective. Further research into HRQoL in Graves' disease could improve the quality of future studies. © 2016 European Society of Endocrinology.

The incidence of ophthalmopathy after radioiodine therapy for Graves` disease: Prognostic factors and the role of methimazole

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

Kung, A.W.C.; Cheng, A.

1994-08-01

Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves` ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves` disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T{sub 4} as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%)more » patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). The authors conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI. 35 refs., 4 tabs.« less

The Brazilian consensus for the diagnosis and treatment of hyperthyroidism: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism.

PubMed

Maia, Ana Luiza; Scheffel, Rafael S; Meyer, Erika Laurini Souza; Mazeto, Glaucia M F S; Carvalho, Gisah Amaral de; Graf, Hans; Vaisman, Mario; Maciel, Lea M Z; Ramos, Helton E; Tincani, Alfio José; Andrada, Nathalia Carvalho de; Ward, Laura S

2013-04-01

Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.

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.

Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

PubMed

Aggarwal, N; Tee, S A; Saqib, W; Fretwell, T; Summerfield, G P; Razvi, S

2016-12-01

Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. Prospective study from August 2010 to December 2014. Endocrinology outpatient clinic in a single centre. Consecutive patients (n = 206) with newly diagnosed GD. ATD therapy. Prevalence and factors predicting neutropenia (<2 × 10 9 /l) and change in neutrophil counts following ATD. At diagnosis, 29 (14·1%) of GD individuals had neutropenia. Non-Caucasians [odds ratio (95% CI) of 4·06 (1·14-14·45), P = 0·03] and patients with higher serum thyroid hormone levels [OR 1·07 (1·02-1·13), P = 0·002 for serum FT3] were the only independent predictors of neutropenia. All patients with neutropenia had normalized blood neutrophil levels after achieving euthyroidism with ATD therapy. In patients in whom data were available posteuthyroidism (n = 149), change in neutrophil count after achieving euthyroidism was independently related to reduction in thyroid hormone levels (P < 0·01). GD is associated with neutropenia in one in seven patients at diagnosis, especially in non-Caucasians and those with higher serum thyroid hormone levels. Neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy. © 2016 John Wiley & Sons Ltd.

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

2017-01-01

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs. PMID:29333460

Comparative bioavailability of carbimazole and methimazole.

PubMed

Jansson, R; Dahlberg, P A; Lindström, B

1983-10-01

In this study we investigated the oral bioavailability of therapeutic doses of two antithyroid drugs, methimazole and carbimazole, in seven euthyroid subjects. To increase the statistical power deuterium-labeled methimazole was given orally as an internal standard together with the tested drugs. Using a recently described highly sensitive gas chromatographic-mass spectrometric assay for methimazole we found that intake of 15 mg carbimazole resulted in plasma concentrations of methimazole and pharmacokinetic data comparable to intake of an equimolar amount of methimazole, i. e., 9.2 mg. Maximum concentrations of 163 and 149 ng/ml, respectively, were reached in both instances at 0.9 h after intake of 15 mg carbimazole and 10 mg methimazole. The plasma half-life was 5.7 and 5.4 h, respectively. In contrast to previous suggestions the interindividual differences in pharmacokinetics were small. In conclusion, carbimazole was rapidly and totally bioactivated to methimazole, and the drugs should be regarded as equipotent when compared on a molar basis.

[Therapy and prevention of hyperthyroidism].

PubMed

Woenckhaus, U; Girlich, C

2005-12-01

A decreased serum TSH level can be observed in more than 10% of the German population. Although treatment is not mandatory in each of these cases patients with an unrecognized autonomous thyroid dysfunction have a substantial risk of developing thyrotoxicosis when exposed to large amounts of iodine. Thionamid drugs in combination with potassium perchlorate are given for preventive and therapeutic reasons until definitive thyroidectomy or radioiodine therapy is performed. In younger patients Graves' disease is the main cause of hyperthyroidism. Medical treatment with antithyroid drugs is established to render patients euthyroid. Having decreased the dose as far as possible, drug therapy is continued for 12-18 months to achieve a maximum rate of permanent remission. Ongoing clinical research aims to characterize clinical or laboratory predictors associated with a high risk of relapse after medication is stopped. Selenium supplementation is proposed to be a new therapeutic approach for autoimmune thyroid disease. It is already used quite liberally although data of powerful randomized trials are not available.

Influence of dietary iodine on drug-induced hypothyrodism in the rat.

PubMed

Beyssen, M L; Lagorce, J F; Cledat, D; Buxeraud, J

1999-06-01

Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased. Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.944+/-0.96 microg/day for chlorpromazine-tested rats, 3.43+/-1.33 microg/day for clomipramine-tested rats, compared with 2.34+/-0.11 microg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland. We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.

Remission of aplastic anemia induced by treatment for Graves disease in a pediatric patient.

PubMed

Das, Prabodh Kumar; Wherrett, Diane; Dror, Yigal

2007-08-01

Aplastic anemia (AA) is mediated by T-cell autoimmunity in the majority of cases; it is rare and mostly idiopathic in children. We describe a child, who developed AA following Graves' disease which could not be attributed to antithyroid drugs. We hypothesized that both diseases were caused by similar autoimmune process. We monitored the blood counts and did not administer any conventional treatment for AA assuming that the existing anti- hematopoietic stem cell humoral and cellular immunity might subside with induction of remission of Grave's disease. The child went into complete remission with the treatment of the Graves' disease.

Propylthiouracil-induced cutaneous vasculitis. Case presentation and review of the literature.

PubMed

Vasily, D B; Tyler, W B

1980-02-01

A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy.

Rapid Improvement of thyroid storm-related hemodynamic collapse by aggressive anti-thyroid therapy including steroid pulse: A case report.

PubMed

Kiriyama, Hiroyuki; Amiya, Eisuke; Hatano, Masaru; Hosoya, Yumiko; Maki, Hisataka; Nitta, Daisuke; Saito, Akihito; Shiraishi, Yasuyuki; Minatsuki, Shun; Sato, Tatsuyuki; Murakami, Haruka; Uehara, Masae; Manaka, Katsunori; Makita, Noriko; Watanabe, Masafumi; Komuro, Issei

2017-06-01

Heart failure is relatively common in patients with hyperthyroidism, but thyrotoxic cardiomyopathy with poor left ventricular (LV) systolic function is very rare. We experienced a representative case of a patient who presented with severe LV dysfunction related to thyroid storm and needed extracorporeal membrane oxygenation (ECMO) temporally. Thyrotoxic cardiomyopathy. Aggressive antithyroid therapy, including steroid pulse to hyperthyroidism, leads to the dramatic improvement of cardiac function and she was successfully weaned from ECMO. The most outstanding feature of the current case was the rapid decrease of cardiac injury and improvement of cardiac function by strengthening antithyroid therapy, including steroid pulse, without thyroid hormone level normalization. In thyroid storm, various systemic inflammatory reactions have different time courses and among them, the cardiac phenotype emerges in most striking and critical ways.

Idiosyncratic drug-induced agranulocytosis or acute neutropenia.

PubMed

Andrès, Emmanuel; Maloisel, Frédéric

2008-01-01

Idiosyncratic drug-induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0.5 x 10/l. Patients with such severe neutropenia are likely to experience life-threatening and sometimes fatal infections. Over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis or acute neutropenia has remained stable at 2.4-15.4 cases per million, despite the emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia and septic shock in around two thirds of patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count under 0.1 x 10/l are poor prognostic factors. Nevertheless with appropriate management using preestablished procedures, with intravenous broad-spectrum antibiotic therapy and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, healthcare professionals should be aware of this adverse event and its management.

Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves' disease.

PubMed

Kim, Kyung Won; Park, Young Joo; Kim, Tae Yong; Park, Do Joon; Park, Kyong Soo; Cho, Bo Youn

2007-12-01

In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication.

PubMed

Smith, Jessica; Brown, Rosalind S

2007-11-01

To determine the course of thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies (TRAbs) in children and adolescents with Graves' disease treated using antithyroid drugs (ATDs). Retrospective, cross-sectional study of 86 children and adolescents with Graves' disease treated medically for >3 years. Patients with Hashimoto's thyroiditis and idiopathic short stature (n = 30) served as controls. A second-generation enzyme-linked immunosorbent assay (ELISA) for TRAbs was used. Twenty-two out of 23 (95.7%) patients with newly diagnosed Graves' disease, but 0/30 controls, had detectable TRAbs (22.0 +/- 13.5 U/L [mean +/- SD] vs. 0.9 +/- 0.9 U/L, p < 0.0001). Mean TRAb levels decreased with duration of therapy, but even after 13-24 months, TRAbs had normalized in only 3/16 (18.8%) patients. The initial TRAb titer correlated significantly with severity of the initial hyperthyroidism, but did not predict the response to therapy as indicated by the dosage of ATD required to control the hyperthyroidism at 6 and 12 months. Unlike adults, most children and adolescents with Graves' disease require >2 years of ATD treatment before TRAbs are normalized. Although initial TRAb activity reflects disease severity, it does not predict the response to medical therapy. Recommendations as to treatment duration developed for adult patients should not be applied to the young.

Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.

PubMed

Orlov, Steven; Salari, Farnaz; Kashat, Lawrence; Walfish, Paul G

2015-05-01

Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described. We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months. Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.

Thyroid storm following radioactive iodine (RAI) therapy for pediatric graves disease.

PubMed

Rohrs, Henry J; Silverstein, Janet H; Weinstein, David A; Amdur, Robert J; Haller, Michael J

2014-01-01

Female, 11 FINAL DIAGNOSIS: Thyroid storm Symptoms: Diarrhea • tachycardia • tachypnea • tremor • wheezing - Clinical Procedure: - Specialty: - Rare disease. A growing number of pediatric endocrinologists treat Graves disease with radioactive iodine (RAI) therapy due to the typically definitive nature of I-131 therapy. Given the published benefits and perceived low risks of RAI when compared to surgery or long-term anti-thyroid medication, the trend towards therapy with RAI is likely to continue. Nevertheless, RAI is not without significant risk. An 11-year-old girl with newly diagnosed Graves disease received RAI for definitive treatment of her hyperthyroidism. Within 24 hours of receiving I-131, she developed increasing sleepiness and eventually became unresponsive. Upon arrival at the emergency department she had a tonic-clonic seizure and was diagnosed with thyroid storm. Despite best efforts to manage her hyperthyroidism, she suffered a stroke of the left cerebral hemisphere that left her with persistent neurological deficits. Although thyroid storm after thyroid ablation is rare, the significant morbidity and potential mortality of pediatric thyroid storm warrant further studies to determine if children with markedly elevated thyroid hormone concentrations at diagnosis should receive prolonged pretreatment with anti-thyroid drugs. While such an approach may reduce the efficacy of I-131 ablation, it can also reduce and hopefully eliminate the risk of post-ablative thyroid storm.

Interventions for hyperthyroidism pre-pregnancy and during pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2013-11-19

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment). Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently. No trials were included in the review. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

Neurologic improvement without angiographic improvement after antithyroid therapy in a patient with Moyamoya syndrome.

PubMed

Ishigami, Akiko; Toyoda, Kazunori; Suzuki, Rieko; Miyashita, Fumio; Iihara, Koji; Minematsu, Kazuo

2014-01-01

Moyamoya disease with special complications, including Graves' disease, is called as moyamoya syndrome. A 22-year-old Japanese woman had left middle cerebral artery (MCA) territory infarction complicated with Graves' disease. She had right-sided hemiparesis that deteriorated on day 8 with the infarct growth and thyrotoxicosis. On angiogram, the left MCA was occluded at the origin without moyamoya vessels. Positron emission tomography (PET) revealed misery-perfusion phenomenon in the left MCA territory. After initiation of the antithyroid therapy, her hemiparesis became milder. Seventeen months later, her thyroid function was normalized and net-like collateral moyamoya vessels proliferated in the left MCA territory. Misery-perfusion phenomenon persisted on PET. This report is unique in the point of neurologic recovery of the moyamoya patient right after initiation of antithyroid medication without radiological improvement. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

An Autoradiographic Study of the Process of Hormone Formation in the Thyroid Gland Under Various Experimental Conditions

DTIC Science & Technology

1960-09-26

to be a generally recognized mechanism of antithyroid action of thiourea derivatives (Astwood, Frank- lin, Chaikoff, and Lerner, Ya. M. Kabak, I. E...expresses an original point of view concerning the mechanisms of the antithyroid action of thiourea: he considers, that an impoverishment of the thyroid...Vol. 30, No. 5, 31. Boyd, Dzh. A., Avtoradiografiya v biologii i meditsine (Auto- radiography in Biology and Medicine ), Moscow, 1957. Fittszheral’d

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

PubMed

Hurley, P M

1998-08-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

Gestational thyrotoxicosis, antithyroid drug use and neonatal outcomes within an integrated healthcare delivery system.

PubMed

Lo, Joan C; Rivkees, Scott A; Chandra, Malini; Gonzalez, Joel R; Korelitz, James J; Kuzniewicz, Michael W

2015-06-01

Increasing attention has focused on the prevalence and outcomes of hyperthyroidism in pregnancy, given concerns for hepatotoxicity and embryopathy associated with antithyroid drugs (ATDs). In an integrated health care delivery system, we examined the prevalence of thyrotoxicosis and gestational ATD use (propylthiouracil [PTU] or methimazole [MMI]) in women with delivered pregnancies from 1996 to 2010. Birth outcomes were compared among all infants and those born to mothers with diagnosed thyrotoxicosis or ATD therapy during gestation, with examination of ATD-associated hepatotoxicity and congenital malformations in the latter subgroups. Among 453,586 mother-infant pairs (maternal age 29.7±6.0 years, 57.1% nonwhite), 3.77 per 1000 women had diagnosed thyrotoxicosis and 1.29 per 1000 had gestational ATD exposure (86.5% PTU, 5.1% MMI, 8.4% both). Maternal PTU-associated hepatotoxicity occurred with a frequency of 1.80 per 1000 pregnancies. Infants of mothers with diagnosed thyrotoxicosis (odds ratio [OR] 1.28, 95% confidence interval [CI 1.05-1.55]) or gestational ATD use (OR 1.31 [1.00-1.72]) had an increased risk of preterm birth compared to those born to mothers without thyrotoxicosis or ATD. The risk of neonatal intensive care unit (NICU) admission was also higher with maternal thyrotoxicosis (OR 1.30 [1.07-1.59]) and ATD exposure (OR 1.64 [CI 1.26-2.13]), adjusting for prematurity. Congenital malformation rates were low and similar among infants born to mothers with thyrotoxicosis or ATD exposure (30-44 per 1000 infants). Gestational ATD exposure occurred in 1.29 per 1000 mother-infant pairs while a much larger number had maternal diagnosed thyrotoxicosis but no drug exposure during pregnancy. Infants of mothers with gestational ATD use or diagnosed thyrotoxicosis were more likely to be preterm and admitted to the NICU. The rates of congenital malformation were low for mothers diagnosed with thyrotoxicosis and did not differ by ATD use. Among women with gestational PTU therapy, the frequency of PTU-associated hepatotoxicity was 1.8 per 1000 delivered pregnancies. These findings from a large, population-based cohort provide generalizable estimates of maternal and infant risks associated with maternal thyrotoxicosis and related pharmacotherapy.

Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

PubMed

Feely, J; Peden, N

1984-05-01

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)

THYROID HORMONE RECEPTOR BETA GENE MUTATION (P453A) IN A TURKISH FAMILY PRODUCING RESISTANCE TO THYROID HORMONE

PubMed Central

Bayraktaroglu, Taner; Noel, Janet; Mukaddes, Nahit Motavalli; Refetoff, Samuel

2018-01-01

Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH). The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as having multinodular toxic goiter which was treated with antithyroid drugs and partial thyroidectomy. Her younger son had attention deficit hyperactivity disorder and primary encopresis, but normal intellectual quotient. Both had elevated serum iodothyronine levels with nonsuppressed thyrotropin. A mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of RTH. PMID:18561095

Onset of reversible flaccid quadriplegia during treatment of thyrotoxic crisis.

PubMed

Mizokami, Tetsuya; Fukui, Takuko; Imoto, Hirofumi; Fujii, Hiroki; Sato, Yuichi; Nunoi, Kiyohide; Okamura, Ken

2015-01-01

Two unrelated women were hospitalized for thyrotoxic crisis complicated by multiple organ failure. Both patients were treated with antithyroid drugs and hydrocortisone, as well as insulin for hyperglycemia, and underwent mechanical ventilation with sedation. Flaccid quadriplegia became apparent after each patient completely recovered their level of consciousness once sedation was discontinued on days 6 and 15, respectively. Three to six months of rehabilitation was required for the muscle strength to fully improve in both cases. Thyrotoxicosis in addition to critical illness polyneuromyopathy and the administration of glucocorticoid therapy may have contributed to the onset of quadriplegia in these two cases. Flaccid quadriplegia is one of the serious neuromuscular conditions experienced during the treatment of thyrotoxic crisis.

[Graves' disease in the elderly].

PubMed

Iitaka, Makoto

2006-12-01

Characterization of elderly (> or = 65) patients with Graves' disease (GD) was discussed. Emaciation was the symptom that was most frequently found in elderly patients. The presence of goiter, exophthalmos and increased appetite decreased with age, while weight loss, anorexia and arrhythmia increased. Elderly patients often have serious complications such as congestive heart failure and atrial fibrillation. Serum levels of free T3, free T4 and TSH receptor antibodies were significantly lower in elderly patients. In addition to fewer clinical signs and symptoms of GD in elderly patients, prominent cardiac or gastrointestinal findings may make the diagnosis more difficult. Elderly GD patients should be treated with antithyroid drugs. Radioiodine therapy may be considered after normalization of serum thyroid hormone levels.

Probing the adsorption mechanism in thiamazole bound to the silver surface with Surface-enhanced Raman Scattering and DFT

NASA Astrophysics Data System (ADS)

Biswas, Nandita; Thomas, Susy; Sarkar, Anjana; Mukherjee, Tulsi; Kapoor, Sudhir

2009-09-01

Surface-enhanced Raman scattering (SERS) of thiamazole have been investigated in aqueous solution. Thiamazole is an important anti-thyroid drug that is used in the treatment of hyperthyroidism (over activity of the thyroid gland). Due to its medicinal importance, the surface adsorption properties of thiamazole have been studied. The experimental Raman and SERS data are supported with DFT calculations using B3LYP functional with LANL2DZ basis set. From the SERS spectra as well as theoretical calculations, it has been inferred that thiamazole is chemisorbed to the silver surface directly through the sulphur atom and the ring N atom, with a tilted orientation.

Hyperthyroidism: diagnosis and management of Graves' disease.

PubMed

Schilling, J S

1997-06-01

Hyperthyroidism, or thyrotoxicosis, results when the body's tissues are exposed to excessive levels of thyroid hormone. Hyperthyroidism affects 2% of women but only one-tenth as many men. Graves' disease is the most common form of hyperthyroidism, often occurring in young adults. It is an autoimmune disorder with an important genetic component. Hyperthyroidism's hallmarks include goiter and myriad signs and symptoms related to increased metabolic activity in virtually all body tissues. Increased sensitivity to circulating catecholamines adds to the clinical picture. Diagnosed by patient history, physical examination, and laboratory tests, Graves' disease is treated with antithyroid drugs, radioactive iodine, and/or surgery, plus supportive therapy. A good treatment outcome can be expected; long-term follow-up is indicated.

Radioiodine therapy versus antithyroid medications for Graves' disease.

PubMed

Ma, Chao; Xie, Jiawei; Wang, Hui; Li, Jinsong; Chen, Suyun

2016-02-18

Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown. To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease. We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases. Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up. Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument. We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I² = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all-cause mortality and bone mineral density were not reported in the included trials. One trial (174 participants) reported socioeconomic effects: costs based on the official hospital reimbursement system in Sweden for patients without relapse and methimazole treatment were USD 1126/1164 (young/older methimazole group) and for radioiodine treatment USD 1862. Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760. The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size.

Antithyroid drugs in Graves' disease: Are we stretching it too far?

PubMed

Jayaraman, Muthukrishnan; Pawah, Anil Kumar; Narayanan, C S

2016-01-01

Early and durable achievement of euthyroid or hypothyroid status with low likelihood of relapse is the key to effective treatment of Graves' disease (GD). Although antithyroid drugs (ATDs) are commonly used first-line agents, likelihood of remission remains highest with radioactive iodine (RAI) therapy and surgery. Data regarding efficacy and economical superiority of RAI therapy over ATDs are lacking from India. This study was designed to study the response to long-term (>12 months) use of ATDs in GD with respect to attainment of remission and to compare the cost of treatment with ATDs versus RAI therapy beyond 12 months. The study was conducted in a tertiary care center. This was a retrospective analysis. Patients of GD in our follow-up from February 2009 to March 2016 who had received ATDs for a duration exceeding 12 months were retrospectively analyzed. Patients who underwent radioablation after a period of at least 12 months on ATDs were analyzed and their status was recorded after a minimum of 6 months after radioablation. Patients who remained hyperthyroid beyond 12 months and received RAI therapy were further compared with those who continued on ATDs, for achievement of euthyroid or hypothyroid status. Cost analysis was done for follow-ups and treatment and compared. All analyses were done using Fisher's exact test for categorical and descriptive statistics for numerical data. Use of ATDs leading to euthyroid and hypothyroid status in GD patients was only significant beyond 24 years when compared to those at <12-18 months therapy ( P = 0.0262 and P = 0.0217, respectively). The patients who ended up with hypothyroid status were significantly greater in RAI group compared to ATD group ( P = 0.0003). Cost of therapy per patient beyond 12 months was lower in the RAI group compared to the ATD group (cost difference Rs. 5435.00). Within limitations, our study demonstrates that RAI is effective and economical option in GD.

The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study.

PubMed

Kim, Ye An; Cho, Sun Wook; Choi, Hoon Sung; Moon, Shinje; Moon, Jae Hoon; Kim, Kyung Won; Park, Do Joon; Yi, Ka Hee; Park, Young Joo; Cho, Bo Youn

2017-04-01

Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients. Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal. During 11.1 years (range 4.0-23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2-1.7], p < 0.001), higher number of relapses (OR = 4.7 [CI 2.3-9.8], p < 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1-15.2], p = 0.032) were associated with persistent disease status. A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

Antithyroid Drug Side Effects in the Population and in Pregnancy.

PubMed

Andersen, Stine Linding; Olsen, Jørn; Laurberg, Peter

2016-04-01

Methimazole (MMI) and propylthiouracil (PTU) are both associated with birth defects and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATDs) are used in the population in general or in pregnancy remains to be elucidated. All individuals registered as the parent of a live-born child in Denmark, 1973–2008, were identified (n = 2 299 952) and studied from 1995 through 2010 for the use of ATDs. Outcomes were agranulocytosis, liver failure, and birth defects in their offspring. To evaluate the frequency of these side effects associated with the use of ATDs in pregnancy, all live-born pregnancies (n = 830 680), 1996–2008, were identified in a subanalysis. In the population studied, 28 998 individuals redeemed prescriptions of ATDs (exposure in 2115 pregnancies), which was associated with 45 cases of agranulocytosis (one in pregnancy) and 10 cases of liver failure (one in pregnancy). This corresponded to 41 and 11 cases of agranulocytosis and liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATDs exposed [MMI: 0.11% vs PTU: 0.27%, P = .02]; liver failure: 0.03% of ATDs exposed [MMI: 0.03% vs PTU: 0.05%, P = .4]). The majority (83%) developed the side effect within 3 months of ATD treatment and 25% during hyperthyroidism relapse. The use of ATDs in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases per 5 million inhabitants per 10 y), and the frequency of birth defects after ATD exposure was 75 times higher than both maternal agranulocytosis and liver failure in pregnancy. In the Danish population in general, ATDs associated birth defects and agranulocytosis had similar frequencies and were more common than liver failure, whereas for the use of ATDs in pregnancy, birth defects were dominant. The burden of side effects to the use of ATDs can be reduced by restricting the use of ATDs in early pregnancy.

Antithyroid drugs in Graves’ disease: Are we stretching it too far?

PubMed Central

Jayaraman, Muthukrishnan; Pawah, Anil Kumar; Narayanan, C. S.

2016-01-01

Introduction: Early and durable achievement of euthyroid or hypothyroid status with low likelihood of relapse is the key to effective treatment of Graves’ disease (GD). Although antithyroid drugs (ATDs) are commonly used first-line agents, likelihood of remission remains highest with radioactive iodine (RAI) therapy and surgery. Data regarding efficacy and economical superiority of RAI therapy over ATDs are lacking from India. This study was designed to study the response to long-term (>12 months) use of ATDs in GD with respect to attainment of remission and to compare the cost of treatment with ATDs versus RAI therapy beyond 12 months. Settings: The study was conducted in a tertiary care center. Study Design: This was a retrospective analysis. Materials and Methods: Patients of GD in our follow-up from February 2009 to March 2016 who had received ATDs for a duration exceeding 12 months were retrospectively analyzed. Patients who underwent radioablation after a period of at least 12 months on ATDs were analyzed and their status was recorded after a minimum of 6 months after radioablation. Patients who remained hyperthyroid beyond 12 months and received RAI therapy were further compared with those who continued on ATDs, for achievement of euthyroid or hypothyroid status. Cost analysis was done for follow-ups and treatment and compared. Statistical Analysis Used: All analyses were done using Fisher's exact test for categorical and descriptive statistics for numerical data. Results: Use of ATDs leading to euthyroid and hypothyroid status in GD patients was only significant beyond 24 years when compared to those at <12–18 months therapy (P = 0.0262 and P = 0.0217, respectively). The patients who ended up with hypothyroid status were significantly greater in RAI group compared to ATD group (P = 0.0003). Cost of therapy per patient beyond 12 months was lower in the RAI group compared to the ATD group (cost difference Rs. 5435.00). Conclusions: Within limitations, our study demonstrates that RAI is effective and economical option in GD. PMID:27730067

Impact of smoking on the course of Graves' disease after withdrawal of antithyroid drugs.

PubMed

Quadbeck, B; Roggenbuck, U; Janssen, O E; Hahn, S; Mann, K; Hoermann, R

2006-09-01

Cigarette smoking has been reported to alter relapse rate in patients with Graves' disease (GD). However, the predictive effect of smoking in GD patients after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A prospective multicenter trial has previously identified smoking as an independent risk factor for relapse. Based on this study, the present paper gives a more detailed analysis of the impact of smoking on the long-term course of GD after ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later (visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs. 6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis showed a significantly higher relapse rate in smokers than non-smokers. A subset of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse during follow-up. Among them, smokers more often relapsed than non-smokers irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10 IU/L the predictive values of a positive and negative test for relapse was 68% and 73%, respectively (specificity 95%). In conclusion, we identified two effects by which smoking alters the course of GD. First, smoking is implicated to elevate TRAb levels and therefore increase the risk for relapse during follow-up. Second, smoking is an independent risk factor to worsen the clinical course of both, GD patients with low and high immunological risk to experience relapse after a successful outcome of ATDT. Thus, our data suggest that smoking has modifying immunological consequences and an adverse impact on the course of GD after withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.

Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China.

PubMed

Yang, Jun; Li, Lin-Fa; Xu, Qin; Zhang, Jun; Weng, Wan-Wen; Zhu, Yang-Jun; Dong, Meng-Jie

2015-03-01

Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study.

PubMed

Andersen, Stine Linding; Lönn, Stefan; Vestergaard, Peter; Törring, Ove

2017-10-01

Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Swedish nationwide register-based cohort study. The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI ( n  = 162); PTU ( n  = 218); MMI and PTU ( n  = 66); ATD before or after, but not in pregnancy ( n  = 1551) and non-exposed (never ATD ( n  = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P  = 0.6) or PTU (6.4%, P  = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects ( P  = 0.02). PTU was associated with ear ( P  = 0.005) and obstructive urinary system malformations ( P  = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed ( P  = 0.3), MMI exposed ( P  = 0.4) or PTU exposed ( P  = 0.2). MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed. © 2017 European Society of Endocrinology.

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.

PubMed

Ross, Douglas S; Burch, Henry B; Cooper, David S; Greenlee, M Carol; Laurberg, Peter; Maia, Ana Luiza; Rivkees, Scott A; Samuels, Mary; Sosa, Julie Ann; Stan, Marius N; Walter, Martin A

2016-10-01

Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Steroid-Responsive Chronic Schizophreniform Syndrome in the Context of Mildly Increased Antithyroid Peroxidase Antibodies.

PubMed

Endres, Dominique; Perlov, Evgeniy; Riering, Anne Nicole; Maier, Viktoria; Stich, Oliver; Dersch, Rick; Venhoff, Nils; Erny, Daniel; Mader, Irina; Tebartz van Elst, Ludger

2017-01-01

Schizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a secondary immunological form associated with increased thyroid antibodies, such as antithyroid peroxidase antibodies and shows a good response to corticosteroids. We present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exacerbations with formal thought disorder, acoustic hallucinations, cenesthopathic experiences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic medication. Her levels of antithyroid peroxidase antibodies were slightly increased, and the blood-brain barrier was disturbed. An electroencephalogram (EEG) showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI) depicted mild temporolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations. SREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of antithyroid peroxidase antibodies in combination with the EEG slowing, blood-brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive deficits were successfully treated with corticosteroids. The occurrence of secondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options.

Risk factors for neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.

PubMed

Uenaka, Mizuki; Tanimura, Kenji; Tairaku, Shinya; Morioka, Ichiro; Ebina, Yasuhiko; Yamada, Hideto

2014-06-01

To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension. The 31 pregnancies resulting in live births were also divided into two groups: neonatal thyroid dysfunction (n=9) and normal neonatal thyroid function (n=22). Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH-receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of antithyroid medication, and the duration of maternal antithyroid medication throughout pregnancy were compared. There were no significant differences in these factors between pregnancies with an adverse pregnancy outcome and those with no adverse pregnancy outcome. However, serum levels of FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose of antithyroid medication, and the total dose of antithyroid medication were significantly different between pregnancies with neonatal thyroid dysfunction and those with normal neonatal thyroid function. Multivariate logistic regression analysis showed that the FT4 level in mothers was a significant factor related to the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence interval 1.65-503.62, p<0.05). Graves' disease activity in women of childbearing age should be well controlled prior to conception. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2014-12-01

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

A case of methimazole-induced chronic arthritis masquerading as seronegative rheumatoid arthritis.

PubMed

Gruber, Conor N; Finzel, Kathleen; Gruber, Barry L

2014-06-01

We report a 40-year-old woman with onset of oligoarthritis shortly after initiating treatment with methimazole for Graves disease. Over the course of 7 years, her arthritis became progressively severe, leading to a diagnosis of seronegative rheumatoid arthritis. Treatment with disease-modifying antirheumatic agents and surgical intervention was contemplated. Ultrasound and magnetic resonance imaging revealed exuberant synovitis, involving right elbow and knees. Upon withdrawal of methimazole, prompt resolution of all signs and symptoms of arthritis was observed within several weeks. Following a MEDLINE search of available literature concerning antithyroid drug-induced arthritis, it is evident that this case represents the lengthiest duration of inflammatory arthropathy ever described in a patient that nonetheless was rapidly reversible with discontinuation of methimazole.

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone: A case report.

PubMed

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-07-01

Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Relative hypothyroidism-induced myopathy. Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases.

Autoimmune thyroid disease in pregnancy: a review.

PubMed

Galofre, Juan C; Davies, Terry F

2009-11-01

The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%-15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T(4)) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L.

Autoimmune Thyroid Disease in Pregnancy: A Review

PubMed Central

Galofre, Juan C.

2009-01-01

Abstract The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%–15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T4) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L. PMID:19951221

Red cell changes in hyperthyroidism.

PubMed

How, J; Davidson, R J; Bewsher, P D

1979-10-01

The Coulter 'S' red cell profile was studied prospectively in 100 untreated non-anaemic hyperthyroid patients and followed up in 52 of them until they had become euthyroid with radio-iodine or carbimazole treatment. Serial haematological data were also obtained in 23 hyperthyroid patients during treatment with beta-adrenoreceptor blocking drug alone. The most significant finding was a low mean corpuscular volume (MCV) which was invariably present throughout the hyperthyroid state. Treatment with beta-adrenoreceptor blocking drugs did not significantly alter any of the red cell parameters. On the other hand, the MCV increased and was restored to normal with radio-iodine or carbimazole treatment although there was a lag period of about 6--8 weeks between achieving the euthyroid state and the normalisation of this red cell index. While none of the patients were aneaemic, the haemoglobin level rose significantly following effective anti-thyroid treatment. It is suggested that measurement of the MCV may have a useful role in the diagnosis of hyperthyroidism. 2 possible mechanisms leading to the observed red cell changes in hyperthyroidism are postulated.

Thyroid storm. A review of cases at University of California, San Francisco.

PubMed

Roizen, M; Becker, C E

1971-10-01

Retrospective study of the diagnosis and management of the 8 cases of thyroid storm in a series of 400 hyperthyroid patients led to conclusion that thyroid storm is a clinical diagnosis based on a life-endangering illness in a hyperthyroid patient whose hyperthyroidism has been severely exacerbated by a serious precipitating illness, and that storm is manifest by the symptoms of hyperpyrexia, tachycardia and striking alterations in consciousness. No laboratory tests were diagnostic of storm, and the underlying precipitating cause of thyroid storm was the major determinant of survival. Vigorous therapy must include blocking synthesis of thyroid hormones with antithyroid drugs, blocking release of preformed hormone with iodine, meticulous attention to hydration and supportive therapy, as well as correction of precipitating cause of storm. The blocking of the sympathetic nervous system with reserpine or guanethidine or with alpha and beta blocking drugs may be exceedingly hazardous and requires skillful management and constant monitoring in a critically ill patient.

Serum immunoglobulin G4 levels and Graves' disease phenotype.

PubMed

Martin, Carmen Sorina; Sirbu, Anca Elena; Betivoiu, Minodora Andreea; Florea, Suzana; Barbu, Carmen Gabriela; Fica, Simona Vasilica

2017-02-01

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

Delayed recovery of left ventricular function after antithyroid treatment. Further evidence for reversible abnormalities of contractility in hyperthyroidism.

PubMed Central

Forfar, J C; Matthews, D M; Toft, A D

1984-01-01

Sequential measurements of systolic time intervals, left ventricular dimensions, and the derived indices of contractility were undertaken at rest and during isometric exercise in 15 hyperthyroid patients before, during, and after antithyroid treatment. At rest hyperthyroidism was characterised by a shortened pre-ejection period and increased velocity of circumferential shortening of the left ventricle. During isometric exercise, however, the pre-ejection period increased significantly beyond that predicted for normal subjects, and the velocity of circumferential fibre shortening fell by 30%. In contrast, both the pre-ejection period and the velocity of circumferential fibre shortening were unchanged during exercise after a stable euthyroid state had been achieved for at least three months. Comparison between exercise responses and thyroid status during antithyroid treatment showed that a biochemical euthyroid state may be achieved many weeks before normalisation of contractile response to exercise. These findings support the hypothesis of reversible depression of left ventricular function in hyperthyroidism. Responses at rest principally reflect the peripheral actions of thyroid hormone excess. PMID:6743439

Gestational Thyrotoxicosis, Antithyroid Drug Use and Neonatal Outcomes Within an Integrated Healthcare Delivery System

PubMed Central

Rivkees, Scott A.; Chandra, Malini; Gonzalez, Joel R.; Korelitz, James J.; Kuzniewicz, Michael W.

2015-01-01

Background: Increasing attention has focused on the prevalence and outcomes of hyperthyroidism in pregnancy, given concerns for hepatotoxicity and embryopathy associated with antithyroid drugs (ATDs). Methods: In an integrated health care delivery system, we examined the prevalence of thyrotoxicosis and gestational ATD use (propylthiouracil [PTU] or methimazole [MMI]) in women with delivered pregnancies from 1996 to 2010. Birth outcomes were compared among all infants and those born to mothers with diagnosed thyrotoxicosis or ATD therapy during gestation, with examination of ATD-associated hepatotoxicity and congenital malformations in the latter subgroups. Results: Among 453,586 mother–infant pairs (maternal age 29.7±6.0 years, 57.1% nonwhite), 3.77 per 1000 women had diagnosed thyrotoxicosis and 1.29 per 1000 had gestational ATD exposure (86.5% PTU, 5.1% MMI, 8.4% both). Maternal PTU-associated hepatotoxicity occurred with a frequency of 1.80 per 1000 pregnancies. Infants of mothers with diagnosed thyrotoxicosis (odds ratio [OR] 1.28, 95% confidence interval [CI 1.05–1.55]) or gestational ATD use (OR 1.31 [1.00–1.72]) had an increased risk of preterm birth compared to those born to mothers without thyrotoxicosis or ATD. The risk of neonatal intensive care unit (NICU) admission was also higher with maternal thyrotoxicosis (OR 1.30 [1.07–1.59]) and ATD exposure (OR 1.64 [CI 1.26–2.13]), adjusting for prematurity. Congenital malformation rates were low and similar among infants born to mothers with thyrotoxicosis or ATD exposure (30–44 per 1000 infants). Conclusions: Gestational ATD exposure occurred in 1.29 per 1000 mother–infant pairs while a much larger number had maternal diagnosed thyrotoxicosis but no drug exposure during pregnancy. Infants of mothers with gestational ATD use or diagnosed thyrotoxicosis were more likely to be preterm and admitted to the NICU. The rates of congenital malformation were low for mothers diagnosed with thyrotoxicosis and did not differ by ATD use. Among women with gestational PTU therapy, the frequency of PTU-associated hepatotoxicity was 1.8 per 1000 delivered pregnancies. These findings from a large, population-based cohort provide generalizable estimates of maternal and infant risks associated with maternal thyrotoxicosis and related pharmacotherapy. PMID:25747892

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

Ogawa, E.; Suzuki, S.; Tsuzuki, H.

Mice were subcutaneoulsy injected with Sr/sup 90/ or Sr/sup 85/, and effects of various drugs on their 3-day excretion and retention on the 4th day were investigated. Among chelating agents, NaCa citrate, NaMg citrate, NaSr citrate, Achromycin (or tetracycline), and aspartic MgK (alone or in combination with NH/sub 4/Cl) displayed Sr-eliminating effects. ATP increased only the excretion without diminishing the retention in bone. EDTA, DTPA, BADE, tricarballylate, Na citrate and NaPb citrate were not effective. Among salts, Mg salt, sulfite, and thiosulfate were effective in eliminating Sr. The last exerted a greater effect when given concurrently with Mg, Ca, ormore » Sr salt. Ca and Sr salt exerted no effect, and ammonium chloride promoted only urinary secretion, not extending to local or total excretion. Such salts as induce alkalosis conversely exerted inhibitory effects. Among hormones, glucocorticoids had Sreliminating effects. TSH was effective, and antithyroidal drugs conversely seemed to have excretion-diminishing effects. Among vitamins, cocarboxylase increased Sr excretion, but did not decrease the retention in bone. Also metabolic inhibitors were ineffective, and NaF conversely increased bone deposition of Sr. Among diuretics, SHdrugs, and weak chelating agents, there were no effective drugs. (JAIF)« less

Graves' disease in 2.5 years old girl - 6-years-long observation.

PubMed

Jonak, Olimpia; Połubok, Joanna; Barg, Ewa

2016-01-01

Pediatric Graves' disease is rare in young children, more frequent in children with other autoimmune diseases or with family history of autoimmune thyroid disease. The 2.5 year old girl was admitted to the hospital with tachycardia and subfebrile temperature. The girl presented symptoms of atopic dermatitis. Child's mother was diagnosed with Hashimoto disease two months after the child's diagnosis. In physical examination of the child, enlarged thyroid was found. At the admission, the laboratory tests revealed decreased TSH (0.001 uIU/ml), increased both FT3 (>30 pg/ml) and FT4 (3.43 ng/dl), but normal levels of anti-thyreoglobulin antibodies (ATG - 0.64 IU/ml) and anti-thyroid peroxidase antibodies (ATPO - 0 IU/ml); thyrotropin receptor antibodies (TRAb) were not identified. The Graves' disease was diagnosed. The girl started treatment with methimazole (2x5mg) and propranolol (due to tachycardia, 2x5mg). The thyroid function (TSH, FT4 and FT3) normalized 1 year after diagnosis and hormone levels remained within normal reference values, but she received methimazole for 18 months. At presen, the patient is 8 years old. She is not receiving any treatment and her thyroid function is correct. The girl still presents symptoms of atopy. In case of symptoms of tachycardia in children, the hyperthyroidism should be taken into consideration. Numerous methods of treatment provide a therapy appropriate to the age and condition of patients. Long remission after treatment with antithyroid drugs could also be achieved in younger (prepubertal) children. © Polish Society for Pediatric Endocrinology and Diabetology.

Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters

PubMed Central

Anila, KR; Nayak, Nileena; Jayasree, K

2016-01-01

Introduction: Chronic lymphocytic thyroiditis [Hashimoto thyroiditis (HT)] is a common thyroid lesion diagnosed on fine-needle aspiration cytology (FNAC). Apart from FNAC, various other parameters, such as clinical features, ultrasonographic findings, antithyroid antibody levels, hormone profiles, and radionuclide thyroid scan, are also taken into consideration in making a diagnosis of HT. Aims: To grade lymphocytic thyroiditis based on the cytomorphology and to correlate the cytological grades with the levels of antithyroid peroxidase antibody (ATPO), antithyroglobulin antibody (ATG), and thyroid stimulating hormone (TSH). Materials and Methods: During a period of one and half years, 1,667 cases underwent FNAC of thyroid at our tertiary care center. Of these, 128 cases had cytological evidence of lymphocytic thyroiditis. Out of these, in 60 cases the levels of ATPO, ATG, and TSH were known. The cytological grades of lymphocytic thyroiditis in these cases were correlated with these parameters. Results: Out of the 60 cases, 55 were females. Age ranged from 5 years to 70 years, with majority of patients in third decade. Diffuse enlargement of thyroid was the commonest presentation. However, 14 cases presented with nodular disease. Majority of the patients had grade 1 thyroiditis (27 cases), followed by grade 2 thyroiditis (22 cases). Cytomorphology was diagnostic of thyroiditis in all 60 cases. ATPO was elevated in 57 cases and ATG was elevated in 40 cases. Elevated level of TSH was seen in only 18 cases. In 39 cases, TSH value was normal. There was no correlation between the cytological grades of thyroiditis and the levels of antithyroid antibodies and TSH. Conclusion: Lymphocytic infiltration of thyroid follicles is pathognomonic of lymphocytic thyroiditis. Positivity for antithyroid antibodies is strongly associated with HT but no correlation was observed between the grades of thyroiditis and the levels of ATPO, ATG, and TSH. PMID:27756987

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone

PubMed Central

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-01-01

Abstract Rationale: Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. Patient concerns: We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Diagnoses: Relative hypothyroidism-induced myopathy. Interventions: Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. Outcomes: The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Lessons: Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases. PMID:28746208

A report of three cases of untreated Graves' disease associated with pancytopenia in Malaysia.

PubMed

Rafhati, Abdullah Noor; See, Chee Keong; Hoo, Fan Kee; Badrulnizam, Long Bidin Mohamed

2014-01-01

Generally, clinical presentations of Graves' disease range from asymptomatic disease to overt symptomatic hyperthyroidism with heat intolerance, tremor, palpitation, weight loss, and increased appetite. However, atypical presentation of Graves' disease with hematological system involvement, notably pancytopenia, is distinctly uncommon. Hereby, we present and discuss a series of three untreated cases of Graves' disease clinically presented with pancytopenia and the hematological abnormalities that responded well to anti-thyroid treatment. With resolution of the thyrotoxic state, the hematological parameters improved simultaneously. Thus, it is crucial that anti-thyroid treatment be considered in patients with Graves' disease and pancytopenia after a thorough hematological evaluation.

Characteristics of Antithyroid Drug-Induced Agranulocytosis in Patients with Hyperthyroidism: A Retrospective Analysis of 114 Cases in a Single Institution in China Involving 9690 Patients Referred for Radioiodine Treatment Over 15 Years.

PubMed

Yang, Jun; Zhu, Yang-Jun; Zhong, Ji-Jun; Zhang, Jun; Weng, Wan-Wen; Liu, Zhen-Feng; Xu, Qin; Dong, Meng-Jie

2016-05-01

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood. Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed. The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 ± 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 ± 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 ± 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13). This largest single-institution study in China shows that ATD-induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach.

Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China.

PubMed

He, Yayi; Zheng, Jie; Zhang, Qian; Hou, Peng; Zhu, Feng; Yang, Jian; Li, Wenhao; Chen, Pu; Liu, Shu; Zhang, Bao; Shi, Bingyin

2017-09-20

Antithyroid drug (ATD)-induced agranulocytosis is associated with human leukocyte antigen (HLA) and nearby genes in Southeast Asian and European populations. The susceptibility of the Han population from northern China to ATD-induced agranulocytosis has not been reported. We evaluated the associations of genetic variants at the HLA-B and HLA-DRB1 loci and 32 candidate single nucleotide polymorphisms (SNPs) with agranulocytosis in 29 patients with ATD-induced agranulocytosis and in 140 patients with Graves' disease (GD) as controls. All subjects were of Han descent from northern China. HLA-B*27:05 (P = 1.10 × 10 -4 ), HLA-B*38:02 (P = 2.41 × 10 -4 ) and HLA-DRB1*08:03 (P = 1.57 × 10 -3 ) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying the HLA-B*27:05 allele had agranulocytosis. The odds ratios (ORs) comparing allele carriers to non-carriers were 66.24 (95% confidence interval (CI): 3.54-1239.66) for HLA-B*27:05, 7.525 (95% CI: 2.294-24.68) for HLA-B*38:02 and 4.316 (95% CI: 1.56-11.93) for HLA-DRB1*08:03. Two SNPs, rs2596487 (OR = 4.196, 95% CI = 2.086-8.441, P = 2.08 × 10 -5 ) and rs2228391 (OR = 3.621, 95% CI = 1.596-8.217, P = 1.2 × 10 -3 ), were independently associated with ATD-induced agranulocytosis. Subjects carrying the 'A' allele of rs1811197 or HLA-B*38:02 showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10 -4 and P = 7.39 × 10 -4 , respectively). Our findings support the association between genetic variations of HLA-B and HLA-DRB1 with ATD-induced agranulocytosis in a Han population from northern China.

A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves' patients undergoing antithyroid drug (ATD) treatment.

PubMed

Giuliani, Cesidio; Cerrone, Dominique; Harii, Norikazu; Thornton, Mark; Kohn, Leonard D; Dagia, Nilesh M; Bucci, Ines; Carpentieri, Maria; Di Nenno, Barbara; Di Blasio, Andrea; Vitti, Paolo; Monaco, Fabrizio; Napolitano, Giorgio

2012-07-01

A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD). The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD. An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period. GD patients from the Chieti University participated in this study. Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay. The Mc4 assay, a sensitive index of remission and recurrence, was used in this study. The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively. The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.

The efficacy of immunosuppressive treatment of Graves' orbitopathy is not affected by previous anti-thyroid drugs or by radioiodine therapy of Graves' disease.

PubMed

Jagiełło-Korzeniowska, Agnieszka; Sokołowski, Andrzej; Krzentowska-Korek, Anna; Miklaszewska, Grażyna; Bałdys-Waligórska, Agata

2016-01-01

We studied the efficacy of immunosuppressive treatment of GO in a group of patients who had been treated with antithyroid drugs (the ATD group) and in another group that had undergone radioiodine therapy (the 131-I group). A total of 214 patients with exacerbation of GO were studied; the ATD group consisting of 168 patients, and the 131-I group consisting of 46 patients. All patients were treated with methylprednisolone IV pulses (total dose 8.0 g) followed by orbital irradiation (20 Gy in 10 fractions). CAS and IO indices, TSH, fT4, and TRAb levels were evaluated prior to, and 1, 6, and 12 months after treatment. One month after treatment the CAS index decreased significantly in both groups, against values before treatment, p < 0.05. In the ATD group the median level of TRAb-0 before treatment was 5.6 IU/L (min = 0.1; max = 114.0), and 12 months later (TRAb-12) it was 1.4 IU/L (min = 0.1; max = 75.3) (p < 0.05). In the 131-I group the median level of TRAb-0 was 14.3 IU/L (min = 0.6; max = 90.0) vs. TRAb-12 of 3.65 IU/L (min = 0.1; max = 41.0) (p < 0.05). In the ATD group the median value of IO-0 before treatment was 5.0 (min = 1.0; max = 12.0) vs. IO-12 of 2.0 (min = 0.0; max = 8.0) (p < 0.05). In the 131-I group the median value of IO-0 was 5.0 (min = 2.0; max = 9.0) vs. IO-12 of 2.0 (min = 0.0; max = 6.0) (p < 0.05). The severity of GO in the ATD and 131-I groups did not differ significantly over the course of observation despite differences noted in their TRAb levels. The efficacy of GO treatment did not differ between these groups. (Endokrynol Pol 2016; 67 (6): 554-561).

Structural characterization of selenium and selenium-diiodine analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives.

PubMed

Antoniadis, Constantinos D; Blake, Alexander J; Hadjikakou, Sotiris K; Hadjiliadis, Nick; Hubberstey, Peter; Schröder, Martin; Wilson, Claire

2006-08-01

The structures of four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil [systematic name: 2,3-dihydro-6-n-propyl-2-thioxopyrimidin-4(1H)-one], namely 6-methyl-2-selenouracil, C(5)H(6)N(2)OSe (1), 6-ethyl-2-selenouracil, C(6)H(8)N(2)OSe (2), 6-n-propyl-2-selenouracil, C(7)H(10)N(2)OSe (3), and 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe (4), are described, along with that of the dichloromethane monosolvate of 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe.CH(2)Cl(2) (4.CH(2)Cl(2)). The extended structure of (1) is a two-dimensional sheet of topology 6(3) with a brick-wall architecture. The extended structures of (2) and (4) are analogous, being based on a chain of eight-membered R(8)(6)(32) hydrogen-bonded rings. In (3) and (4.CH(2)Cl(2)), R(2)(2)(8) hydrogen bonding links molecules into chains. 6-n-Propyl-2-selenouracil.I(2), C(7)H(10)N(2)OSe.I(2) (7), is a charge-transfer complex with a ;spoke' structure, the extended structure of which is based on a linear chain formed principally by intermolecular N-H...O hydrogen bonds. Re-crystallization of 6-ethyl-2-selenouracil or (7) from acetone gave crystals of the diselenides [N-(6'-ethyl-4'-pyrimidone)(6-ethyl-2-selenouracil)(2)(Se-Se)].2H(2)O (9.2H(2)O) or [N-(6'-n-propyl-4'-pyrimidone)(6-n-propyl-2-selenouracil)(2)(Se-Se)] (10), respectively: these have similar extended chain structures formed via N-H...O and C-H...O hydrogen bonds, stacked to give two-dimensional sheets. Re-crystallization of (7) from methanol/acetonitrile led via deselenation to the formation of crystals of 6-n-propyl-2-uracil (11), in which six symmetry-related molecules combine to form a six-membered R(6)(6)(24) hydrogen-bonded ring, with each pair of molecules linked by an R(2)(2)(8) motif.

Pharmacologic treatment of hyperthyroidism during pregnancy.

PubMed

Cassina, Matteo; Donà, Marta; Di Gianantonio, Elena; Clementi, Maurizio

2012-08-01

Clinical hyperthyroidism has been associated with an increased risk of maternal, fetal, and neonatal complications. The available antithyroid drugs are methimazole/carbimazole and propylthiouracil. Several case reports and some epidemiologic studies suggest that methimazole/carbimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele. However, the absolute risk appears to be very small, and it remains unclear whether the association is driven by the maternal disease, the medication, or the combination of both factors. Propylthiouracil exposure has not been associated with an increased risk of congenital malformations and is the recommended drug during the first trimester of pregnancy. Since propylthiouracil-induced hepatotoxicity has been reported in approximately 0.1% of exposed adults and the number of case-reports of severe liver injury is increasing, treatment with low dose methimazole during the second and third trimesters should be considered. Until now, there has been no evidence that children prenatally exposed to methimazole/carbimazole or propylthiouracil have an increased risk of neurodevelopmental delay. Copyright © 2012 Wiley Periodicals, Inc.

Wenxin Keli versus Sotalol for Paroxysmal Atrial Fibrillation Caused by Hyperthyroidism: A Prospective, Open Label, and Randomized Study

PubMed Central

Meng, Zhaowei; Tan, Jian; He, Qing; Zhu, Mei; Li, Xue; Zhang, Jianping; Jia, Qiang; Wang, Shen; Zhang, Guizhi; Zheng, Wei

2015-01-01

We aimed to compare effectiveness of Wenxin Keli (WK) and sotalol in assisting sinus rhythm (SR) restoration from paroxysmal atrial fibrillation (PAF) caused by hyperthyroidism, as well as in maintaining SR. We randomly prescribed WK (18 g tid) or sotalol (80 mg bid) to 91 or 89 patients. Since it was not ethical not to give patients antiarrhythmia drugs, no control group was set. Antithyroid drugs were given to 90 patients (45 in WK group, 45 in sotalol group); 131I was given to 90 patients (46 in WK group, 44 in sotalol group). Three months later, SR was obtained in 83/91 or 80/89 cases from WK or sotalol groups (P = 0.762). By another analysis, SR was obtained in 86/90 or 77/90 cases from 131I or ATD groups (P = 0.022). Then, we randomly assigned the successfully SR-reverted patients into three groups: WK, sotalol, and control (no antiarrhythmia drug was given) groups. After twelve-month follow-up, PAF recurrence happened in 1/54, 2/54, and 9/55 cases, respectively. Log-Rank test showed significant higher PAF recurrent rate in control patients than either treatment (P = 0.06). We demonstrated the same efficacies of WK and sotalol to assist SR reversion from hyperthyroidism-caused PAF. We also showed that either drug could maintain SR in such patients. PMID:26074982

Mental health status and factors that influence the course of Graves' disease and antithyroid treatments.

PubMed

Chen, D Y; Schneider, P F; Zhang, X S; He, Z M; Jing, J; Chen, T H

2012-10-01

Biological, psychological and social factors may interact with the mental health status of Graves' disease (GD) patients before and after antithyroid drug (ATD) treatment. Our aim was to quantify the impact of supportive and risk factors after recovery from GD which may enhance cure rates. 300 patients were recruited for a 6-year prospective cohort study. Before and after treatment, we assessed the impact of biopsychosocial factors on the success of ATD treatment and mental health using the Symptom Checklist 90, the Eysenck Personality Questionnaire, the Life Event Scale, Simplified Coping Styles and the Perceived Social Support Scale. The patients routinely received ATD at least over 18 months. End-point was defined as cured (at least 2 years without a relapse after the withdrawal of ATD), otherwise as not cured. Regression analysis explained 80.5% of the influences affecting mental health. The odds ratios (OR) revealed positive coping styles (OR: 2.90, 95% CI, 1.09-7.68), negative events (OR: 1.04, 95% CI, 1.01-1.07) and social support (OR: 5.10, 95% CI, 2.77-9.40) as protective factors, predicting a cure for GD patients. These variables explained 61.7% of the influences leading to a cure or no cure. Large thyroid volume was a risk factor, predicting failure (OR: 0.865, 95% CI, 0.83-0.90, P<0.000). Enhancing positive coping strategies and social support is important to improve mental health in GD patients, to avoid compromising work-related performance and endangering a patient's social status. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels.

PubMed

Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

2014-05-01

There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels

PubMed Central

Uduak, Okon Akpan; Ani, Elemi John; Etoh, Emmauel Columba Inyang; Macstephen, Adienbo Ologbagno

2014-01-01

Background: There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels. Objective: To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH. Materials and Methods: Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. Results: The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control. Conclusion: These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB. PMID:25013255

Effects of an iodine-restricted food on client-owned cats with hyperthyroidism.

PubMed

van der Kooij, Marieke; Bečvářová, Iveta; Meyer, Hein P; Teske, Erik; Kooistra, Hans S

2014-06-01

The objective of this prospective, multicentre, non-controlled, open-label study was to evaluate the effects of an iodine-restricted food on circulating total thyroxine (TT4) concentrations and clinical parameters in client-owned cats with hyperthyroidism. Two hundred and twenty-five cats were enrolled in the study and adapted to the iodine-restricted food. Data from physical examinations, questionnaires completed by veterinarians and owners, and circulating concentrations of TT4, urea and creatinine were recorded at weeks 0, 4 and 8. The study group included 136 female and 89 male cats (median age 15 years, range 4-21 years). Group 1 (n = 113) had been on previous anti-thyroid medication, while group 2 (n = 112) consisted of newly diagnosed cats. No differences were found between the two groups at any time point. Circulating TT4 concentrations had decreased (P <0.0001) at week 4 and did not change significantly from week 4 to week 8. Circulating TT4 concentration was within the reference range in 56/88 cats at week 4 and in 51/68 cats at week 8. Clinical parameters (vomiting, polyuria, polydipsia, hyperactivity, polyphagia, weight loss, hair coat quality, and quality of life) had improved (P <0.0001) by week 4. Circulating creatinine concentration decreased (P = 0.001) from week 0 to week 4. Side effects associated with feeding the iodine-restricted food were not observed. In conclusion, in client-owned cats with hyperthyroidism an iodine-restricted food is a valuable management option to normalise circulating TT4 concentrations, and improve clinical signs of hyperthyroidism within 4 weeks. This applies to newly diagnosed cats, as well as to previously diagnosed cats receiving anti-thyroid drugs. © ISFM and AAFP 2013.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

Marrow hypoplasia: a rare complication of untreated Grave's disease.

PubMed

Garcia, Juliana; França, Larissa de; Ellinger, Vivian; Wolff, Mônica

2014-12-01

Atypical presentation forms of hyperthyroidism are always a challenge to the clinician. We present a female patient with the typical symptoms of thyrotoxicosis, without any thionamides treatment before, associated with pancytopenia, which recovered after euthyroidism state was achieved. Although the major cases of pancytopenia in Grave's disease are seen as a complication of antithyroid drugs (thioamides), in this case report the alteration in blood tests was associated with untreated hyperthyroidism. In the literature review, we found 19 case reports between 1981 to 2012, but it has been related to a hypercellular bone marrow with periferic destruction. Our case, however, is about a hypocellular bone marrow without fibrosis or fat tissue replacement, which proceeded with a periferic improvement following thyroid treatment. Although rare, pancytopenia, when present, may develop as an unusual and severe manifestation in untreated subjects.

[Iodine 131 joint radio frequency ablation treatment for child with hyperthyroidism goiter: one case report].

PubMed

Chen, Yonghua; Liang, Li; Fang, Yanlan; Wang, Chunlin; Li, Linfa; Jiang, Tian'an

2017-01-25

A 12-year-old girl presented with a history of cervical mass, and one week of throat discomfort and dyspnea. Five years ago, the patient was diagnosed as Hashimoto's thyroiditis and hyperthyroidism; she received antithyroid drug treatment, but the result was not satisfactory. B-ultrasonic showed that the size of thyroid gland was 8.1 cm×3.2 cm in the left and 8.2 cm×4.8 cm in the right. After iodine 131 combined with radiofrequency ablation (RFA) treatment, throat discomfort and recumbent breathing difficulties disappeared, and B-ultrasonic showed that the size of thyroid reduced to 2.3 cm×1.7 cm (left) and 2.8 cm×2.0 cm (right). No recurrence was observed during the two and a half years of follow-up.

[Radioiodine treatment of Graves' disease --for its wider indication and application in Japan].

PubMed

Konishi, Junji

2006-12-01

Radioiodine treatment has been well established as an effective and safe therapeutic modality for Graves' disease. To promote more efficient use of this treatment in Japan, a working group has been organized in the Japan Thyroid Association and preparation of guidelines for its clinical use is under way. The treatment using upto 13.5 mCi of I-131 is feasible on out-patient basis. In comparison to the antithyroid drug treatment, the treatment has no side effects, brings in good control of hyperthyroidism and decrease the size of goiter. It is contraindicated in pregnant and lactating women. Patients treated should be carefully monitored for the possible worsening of ophthalmopathy and neonatal Graves' disease. Recent studies revealed the cost-effectiveness of the treatment. Its application to autonomously functioning thyroid nodules and toxic multinodular goiters is also discussed.

Iodine-Induced Thyrotoxicosis After Ingestion of Kelp-Containing Tea

PubMed Central

Müssig, Karsten; Thamer, Claus; Bares, Roland; Lipp, Hans-Peter; Häring, Hans-Ulrich; Gallwitz, Baptist

2006-01-01

Complementary medication is en vogue and an increasing number of patients consume herbal medicine without reporting their use to physicians. We report a case of iodine-induced hyperthyroidism due to the ingestion of a kelp-containing tea. A 39-year-old woman with multinodular goiter presented with typical signs of hyperthyroidism, which was confirmed by endocrine tests. She was not exposed to iodinated radiocontrast media and did not take medications containing iodine, such as amiodarone. However, a detailed medical history revealed that she had been treated for a period of 4 weeks by a Chinese alternative practitioner with a herbal tea containing kelp because of her enlarged thyroid. The consumption of the tea was discontinued and an antithyroid drug therapy was initiated. Physicians should advise patients with underlying thyroid disease to avoid all complementary or alternative medications containing iodine. PMID:16808731

Experimental hypo/hyperthyroidism in rats and the perinatal development of the hypothalamo-neurohypophysial system in comparison with the thyroid gland state and external features.

PubMed

Kiessig, R; Wolf, G; Dietzmann, K

1983-05-01

Neurophysin was detected immunohistochemically in the hypothalamo-neurohypophysial system of Wistar rats not before fetal day 18. Formerly, neurophysin was identified on day 16 of intrauterine life using another breeding stock of Wistar rats, but the same immunohistochemical reagents. In pregnant rats, experimentally induced hypo/hyperthyroidism beginning with day 13 of gestation failed to show any evident influence on the first appearance of immunohistochemically detectable neurophysin during the fetal development. Otherwise, significant effects on fetal body growth and other external features as well as the fetal thyroid state and histochemically demonstrable thyroid peroxidase activity were shown. The influence of thiamazol on the fetal thyroid peroxidase points out a primary effect and indicates the permeability of the placenta to this antithyroid drug.

A 27-year-old woman diagnosed as polycystic ovary syndrome associated with Graves' disease.

PubMed

Jung, Jung Hwa; Hahm, Jong Ryeal; Jung, Tae Sik; Kim, Hee Jin; Kim, Ho Soo; Kim, Sungsu; Kim, Soo Kyoung; Lee, Sang Min; Kim, Deok Ryong; Choi, Won Jun; Seo, Yeong Mi; Chung, Soon Il

2011-01-01

Polycystic ovary syndrome (PCOS) and Graves' disease are the common causes of menstrual irregularity leading to infertility in women of child-bearing age. A 21-year-old female patient visited us with complaints of oligomenorrhea and hand tremor. She was diagnosed as having PCOS and hyperthyroid Graves' disease, simultaneously. She had low body weight (BMI: 16.4 kg/m(2)), mild hirsutism, and thyrotoxicosis. The patient was treated with anti-thyroid drug and beta-blocker for about two years, and then recovered to normal thyroid function. Although some studies have suggested a connection between PCOS and autoimmune thyroiditis, no study indicated that PCOS is associated with Graves' disease until now. Here, we describe the first case report of a lean woman with normal insulin sensitivity presenting PCOS and Graves' disease simultaneously.

Causes of anorexia in untreated hyperthyroidism: a prospective study

PubMed Central

Dai, W.; Meng, X.

2000-01-01

Seventeen consecutive patients (mean (SD) 46 (11) years) with untreated hyperthyroidism and anorexia and 29 patients (35 (9) years) with untreated hyperthyroidism without anorexia were studied. The study was conducted at the thyroid clinic of the PUMC Hospital, Beijing, China from March to August 1997. The patients' ages, serum free calcium, liver function and emotional state, specifically the level of anxiety (using the self anxiety scale, Chinese version), were compared before and/or after antithyroid drug treatment in the two groups. This prospective study suggested that the causes of anorexia in untreated hyperthyroidism are complicated. Older age, abnormal liver function, and the level of anxiety are significantly related to anorexia in untreated hyperthyroidism, but hypercalcaemia was not confirmed to be related to anorexia in the study.


Keywords: hypercalcaemia; hyperthyroidism; anorexia; anxiety PMID:10775283

[Neonatal hyperthyroidism and maternal Graves disease].

PubMed

Ben Ameur, K; Chioukh, F Z; Marmouch, H; Ben Hamida, H; Bizid, M; Monastiri, K

2015-04-01

The onset of Graves disease during pregnancy exposes the neonate to the risk of hyperthyroidism. The newborn must be monitored and treatment modalities known to ensure early treatment of the newborn. We report on the case of an infant born at term of a mother with Graves disease discovered during pregnancy. He was asymptomatic during the first days of life, before declaring the disease. Neonatal hyperthyroidism was confirmed by hormonal assays. Hyperthyroidism was treated with antithyroid drugs and propranolol with a satisfactory clinical and biological course. Neonatal hyperthyroidism should be systematically sought in infants born to a mother with Graves disease. The absence of clinical signs during the first days of life does not exclude the diagnosis. The duration of monitoring should be decided according to the results of the first hormonal balance tests. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases

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

Hawthorne, G.C.; Campbell, N.P.; Geddes, J.S.

1985-06-01

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. The authors conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop inmore » the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.« less

Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs.

PubMed

Daminet, S; Kooistra, H S; Fracassi, F; Graham, P A; Hibbert, A; Lloret, A; Mooney, C T; Neiger, R; Rosenberg, D; Syme, H M; Villard, I; Williams, G

2014-01-01

Pharmacological management of feline hyperthyroidism offers a practical treatment option for many hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its pro-drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of 2·5 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases should be monitored for side-effects, especially during the first months of treatment. Some side-effects may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life should also be evaluated, with special attention to possible development of azotaemia, hypertension and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre-existing azotaemia have shorter survival times. However, development of mild azotaemia during the initial course of treatment, unless associated with hypothyroidism, does not appear to decrease survival time. The long-term effects of chronic medical management require further study. © 2013 British Small Animal Veterinary Association.

Hypothyroidism during antithyroid drug treatment with methimazole is a favorable prognostic indicator in patients with Graves' disease.

PubMed

Choo, Young Kwang; Yoo, Won Sang; Kim, Dong Woo; Chung, Hyun-Kyung

2010-09-01

A major problem with antithyroid drug (ATD) therapy in Graves' disease is the high relapse rate. Therefore, clinicians have sought prognostic indicators of permanent remission. Suppression of serum thyrotropin (TSH) when ATD therapy is stopped carries a poor prognosis, but little is known regarding the significance of elevated serum TSH concentrations in the course of ATD therapy. The objective of this study was to determine if elevated serum TSH concentrations during methimazole (MMI) therapy is associated with a favorable long-term prognosis. We retrospectively studied patients with Graves' disease who were initially on MMI, in whom this drug was stopped because they had undetectable thyroid-stimulating antibodies (TSAbs) or were euthyroid after at least 24 months on MMI treatment. A strategy of high MMI doses plus T4 was not used in these patients. We identified 40 patients with elevated serum TSH concentration (>10 microIU/mL) during MMI therapy (H-TSH group). Eighty-five percent of the H-TSH group had negative tests for TSAb. The H-TSH group was sex- and age-matched with 37 patients who had similar selection criteria, but did not have elevated serum TSH concentration during MMI therapy (N-TSH group). The H-TSH and N-TSH groups were similar in gross thyroid size, percentage of patients with exophthalmos, serum free thyroxine, duration of MMI treatment, TSAb status, duration that their TSAb tests remained negative, and thyroid peroxidase antibody titers. The patients were followed for 24 months after stopping MMI. In the H-TSH group, MMI-associated hypothyroidism typically occurred after 7-8 months of treatment with daily doses of 10-15 mg MMI. No patient had severe symptoms of hypothyroidism. The percentage of patients in remission at 6, 12, and 24 months after discontinuation of MMI was 90.0, 87.5, and 85.0, respectively, in the H-TSH group and 70.3, 67.6, and 54.1, respectively, in the N-TSH group (p  <  0.05 for the comparison of groups at 6 and 12 months and p  <  0.001 for comparison of the groups at 24 months). In patients with Graves' disease who are treated with MMI for at least 2 years and become euthyroid, the occurrence of elevated serum TSH concentrations during MMI treatment is a favorable indicator for long-term remission and is independent of multiple other factors including TSAb status, duration of MMI treatment, and gross parameters of goiter size.

The selective beta 1-blocking agent metoprolol compared with antithyroid drug and thyroxine as preoperative treatment of patients with hyperthyroidism. Results from a prospective, randomized study.

PubMed Central

Adlerberth, A; Stenström, G; Hasselgren, P O

1987-01-01

Despite the increasing use of beta-blocking agents alone as preoperative treatment of patients with hyperthyroidism, there are no controlled clinical studies in which this regimen has been compared with a more conventional preoperative treatment. Thirty patients with newly diagnosed and untreated hyperthyroidism were randomized to preoperative treatment with methimazole in combination with thyroxine (Group I) or the beta 1-blocking agent metoprolol (Group II). Metoprolol was used since it has been demonstrated that the beneficial effect of beta-blockade in hyperthyroidism is mainly due to beta 1-blockade. The preoperative, intraoperative, and postoperative courses in the two groups were compared, and patients were followed up for 1 year after thyroidectomy. At the time of diagnosis, serum concentration of triiodothyronine (T3) was 6.1 +/- 0.59 nmol/L in Group I and 5.7 +/- 0.66 nmol/L in Group II (reference interval 1.5-3.0 nmol/L). Clinical improvement during preoperative treatment was similar in the two groups of patients, but serum T3 was normalized only in Group I. The median length of preoperative treatment was 12 weeks in Group I and 5 weeks in Group II (p less than 0.01). There were no serious adverse effects of the drugs during preoperative preparation in either treatment group. Operating time, consistency and vascularity of the thyroid gland, and intraoperative blood loss were similar in the two groups. No anesthesiologic or cardiovascular complications occurred during operation in either group. One patient in Group I (7%) and three patients in Group II (20%) had clinical signs of hyperthyroid function during the first postoperative day. These symptoms were abolished by the administration of small doses of metoprolol, and no case of thyroid storm occurred. Postoperative hypocalcemia or recurrent laryngeal nerve paralysis did not occur in either group. During the first postoperative year, hypothyroidism developed in two patients in Group I (13%) and in six patients in Group II (40%). No patient had recurrent hyperthyroidism. The results suggest that metoprolol can be used as sole preoperative treatment of patients with hyperthyroidism without serious intra- or postoperative complications. Although the data indicate that the risk of postoperative hypothyroidism is higher after preoperative treatment with metoprolol than with an antithyroid drug, a longer follow-up period than 1 year is needed to draw conclusions regarding late results. PMID:3545108

Thyroiditis

MedlinePlus

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

[Prevalence of non-thyroid autoantibodies in autoimmune dysthyroidies].

PubMed

Guerin, V; Prestat, F; Bene, M C; Faure, G; Hartemann, P; Leclere, J

1989-01-01

Organ- and non organ-specific autoantibodies can be detected in patients with AITD but large comparative studies have seldom been performed. This study evaluated the prevalence of anti-thyroid, -smooth muscle, -mitochondria, -parietal gastric cells, -salivary duct, -nuclear and -ds DNA autoantibodies assayed by indirect immunofluorescence in 224 patients with Graves' disease or Hashimoto's thyroiditis. Results evidenced a high prevalence of antinuclear antibodies, mostly of non homogenous fluorescence in Graves' (63.1%) and Hashimoto's patients (65.5%), as well as for antisalivary duct antibodies (55.2 and 75%). No positive anti-ds DNA were noticed. No correlation was found between antithyroid antibodies and the others. Different hypothesis could explain this observation which favours a general dysregulation of the autoimmune system.

Outcome of treating thyrotoxic patients with a standard dose of radioactive iodine.

PubMed

Johnson, J K

1993-10-01

This is a report of an audit exercise that was designed to study the effectiveness of treating thyrotoxic patients with a standard dose--370 MBq--of radioactive iodine (131l). This treatment was received by 183 patients in one centre between 1977 and 1989. The results were assessed from the answers to 114 questionnaires that had been completed by the patients' general practitioners. The patients were aged between 28 and 85 years; 86% were female; 42% had been treated previously with anti-thyroid drugs. Ninety-five of the patients (83%) became euthyroid after a single dose of 131l; 18 required one further dose; and one required two further doses. At the time of the survey, 32 (28%) were euthyroid, while 82 patients (72%) had become hypothyroid and required treatment with thyroxine. Within five years of treatment, 85% of the patients had become hypothyroid. These results are compared with those from two other centres.

Important considerations in the management of Graves' disease in pregnant women.

PubMed

Okosieme, Onyebuchi E; Lazarus, John H

2015-01-01

Graves' disease is an autoimmune disorder in which autoantibodies to the thyroid-stimulating hormone receptor cause hyperthyroidism through unregulated stimulation of the thyroid-stimulating hormone receptor. Effective management of Graves' disease in pregnancy must address the competing fetal and maternal priorities of controlling hyperthyroidism in the mother on the one hand, and on the other, minimizing the impact of maternal disease and antithyroid drugs on the well-being of the fetus. Optimal strategies for achieving this intricate balance are currently a source of continued debate among thyroid experts and studies in recent decades are now providing greater clarity into the risk posed to the unborn baby by the combination of biochemical, immunological and pharmacological hazards arising from Graves' disease and its therapy. This review summarizes the current best practice and highlights important considerations and areas of uncertainty in the management of Graves' disease in pregnant women.

Antiphospholipid Antibody Syndrome Associated with Graves’ Disease Presenting As Inferior Vena Cava Thrombosis with Bilateral Lower Limb DVT

PubMed Central

Jain, Ankur

2014-01-01

We report a case of a 60-year-old lady who presented with bilateral lower limb swelling and a thyroid swelling with clinical features consistent with thyrotoxicosis. Investigations revealed the presence of a thrombus in bilateral external, internal iliac veins, and inferior vena cava extending up to its infrahepatic part. Hormone profile and radioiodine uptake scan confirmed the diagnosis of Graves’ disease. Further workup revealed the presence of antiphospholipid antibodies (confirmed after a repeat test at 12 weeks). The patient was treated with antithyroid drugs and anticoagulants. The patient improved with normalization of thyroid function and partial recanalization of the infrahepatic part of inferior vena cava. Hyperthyroidism has been implicated as a potential hypercoagulable state; however, the association of Graves’ disease with antiphospholipid antibody syndrome is limited to isolated case reports. This case highlights a new mechanism underlying hypercoagulability associated with Graves’ disease. PMID:24812529

Hyperthyroidism: an unusual case presentation.

PubMed

Scripture, D L

1998-02-01

Hyperthyroidism is the most common disorder of the thyroid. Patients typically present with complaints consistent with a hypermetabolic state, including nervousness, weight loss, heat intolerance, palpitations, irritability, and tremor. This case report reviews a 34-year-old woman who presented with unilateral upper extremity weakness, weight gain, and an episode of atrial fibrillation, the latter coinciding with a 36-hour lack of sleep and excess alcohol and caffeine intake. Although an extensive neurologic evaluation failed to identify any abnormality, the patient's laboratory analysis revealed elevations in thyroxine (T4) and triiodothyronine (T3) levels with unsuppressed thyroid-stimulating hormone levels. Subsequent treatment with the antithyroid drug methimazole (Tapazole) provided complete relief of symptoms. This case report illustrates how health care providers can be diverted to pursue a neurologic etiology when muscle weakness presents as a unilateral symptom. Plausible alternative causes for muscle weakness and other symptoms are presented.

[Anesthetic management using esmolol for arthroscopic synovectomy in a patient with thyroid storm].

PubMed

Torigoe, Kei; Suzuki, Hiroto; Nakajima, Waka; Takahashi, Minori; Aoyagi, Mitsuo

2010-02-01

We report a case of a 47-year-old woman with past medical history of Graves disease who presented with thyroid storm, a state of physiologic decompensation due to severe thyrotoxicosis, and arthritis purulenta. Antithyroid therapy ameliorated thyrotoxicosis in 4 days, and arthroscopic synovectomy of the right knee was performed. Anesthesia was induced with intravenous propofol. Esmolol, an ultra-short-acting beta blocker listed in national drug tariff of Japan for intraoperative continuous iv infusion in March 2008, was also administered to control heart rate. Then, laryngeal mask airway was inserted and echo-guided femoral nerve block was done with ropivacaine. Anesthesia was maintained with i.v. infusion of propofol and fentanyl. Short episode of supraventricular tachycardia occurred twice, but each tachycardia disappered in about a half minute. The postoperative course was uneventful. Esmolol probably acted to prevent intraoperative tachycardia due to increased beta-adrenergic tone.

Is autoimmune thyroid dysfunction a risk factor for gestational diabetes?

PubMed

Pascual Corrales, Eider; Andrada, Patricia; Aubá, María; Ruiz Zambrana, Alvaro; Guillén Grima, Francisco; Salvador, Javier; Escalada, Javier; Galofré, Juan C

2014-01-01

Some recent studies have related autoimmune thyroid dysfunction and gestational diabetes (GD). The common factor for both conditions could be the existence of pro-inflammatory homeostasis. The study objective was therefore to assess whether the presence of antithyroid antibodies is related to the occurrence of GD. Fifty-six pregnant women with serum TSH levels ≥ 2.5 mU/mL during the first trimester were retrospectively studied. Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD was diagnosed based on the criteria of the Spanish Group on Diabetes and Pregnancy. Positive antithyroid antibodies were found in 21 (37.50%) women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using exact logistic regression by LogXact-8 Cytel; no statistically significant differences were found between GD patients with positive and negative autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ≥ 2.5 mU/mL. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Autoantibodies and their clinical significance in a black vitiligo population.

PubMed

Grimes, P E; Halder, R M; Jones, C; Chakrabarti, S G; Enterline, J; Minus, H R; Kenney, J A

1983-04-01

The frequency of autoantibodies was determined in 70 black vitiligo patients and controls. Both groups were screened for antithyroid, antinuclear, antigastric parietal cell, anti-smooth muscle cell, and antimitochondrial autoantibodies. The significance of autoantibodies was determined in vitiligo patients by correlating their presence or absence with various clinical features of the patients. The overall frequencies of autoimmune and endocrine diseases were also assessed in vitiligo patients, controls, and their respective families. Vitiligo patients had an increased frequency of antithyroid antibodies and an increased frequency of autoimmune and/or endocrine diseases. These diseases included, especially, hyperthyroidism, hypothyroidism, and alopecia areata. Autoantibody-positive vitiligo patients had an increased frequency of first- and second-degree relatives having autoimmune and/or endocrine diseases. These findings tend to support an autoimmune cause of vitiligo in black patients.

[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.

Current trends in antithyroid drug treatment of Graves' disease.

PubMed

Okosieme, Onyebuchi E; Lazarus, John H

2016-10-01

Graves' hyperthyroidism is associated with significant morbidity and mortality risk. The thionamides, methimazole, its pro-drug derivative carbimazole, and propylthiouracil, remain a cornerstone of management. Yet despite decades of use, optimal strategies for maximising treatment response and curtailing adverse effect risk remains uncertain. We reviewed the current literature on the evidence based medical management of Graves' disease. Specifically, we evaluated current approaches to the use of thionamides, adjunctive therapies, and potential novel agents for controlling Graves' hyperthyroidism. Primary medical therapy is successful in less than 50% of cases and so careful selection of patients for medical treatment based on a combination of pathological and pragmatic considerations is essential. Carbimazole or methimazole is the treatment of choice in the non-pregnant population driven by its more favourable pharmacokinetic and adverse effect profile over propylthiouracil. In pregnancy the choice of treatment is less straightforward and an approach that minimises undue fetal exposure to all thionamides should be adopted. Additional data is needed on the value of adjunctive therapies including potassium perchlorate, iodides, glucocorticoids, lithium, and cholestyramine. Novel agents directed against pathogenetic targets including TSH receptor blocking monoclonal antibodies and small molecule antagonists may hold promise for the future.

A rare case of methimazole-induced cholestatic jaundice in an elderly man of Asian ethnicity with hyperthyroidism: A case report.

PubMed

Ji, Hongjian; Yue, Feng; Song, Jianxiang; Zhou, Xiaohua

2017-12-01

Methimazole is an antithyroid drug that is widely used for the treatment of hyperthyroidism. As an inhibitor of the enzyme thyroperoxidase, methimazole is generally well-tolerated. However, there have been increasing reports of methimazole-induced liver damage, although this effect of methimazole has been limited by the absence of objective diagnosis of the liver condition or the inappropriate use of the Naranjo scale. We present the case of an elderly man with hyperthyroidism, gastritis, and epilepsy who developed liver damage after administration of multiple drugs. Considering the low sensitivity of the Naranjo scale in detecting rare reactions associated with liver damage, we used the Roussel-Uclaf Causality Assessment Method scale, with a finding of cholestatic jaundice hepatitis induced by methimazole. The patient's liver enzyme levels improved after discontinuation of methimazole. Our case underlines the possible hepatoxicity associated with the use of methimazole. A review of the literature confirmed a selective hepatoxicity risk in individuals of Asian ethnicity, which has not been identified in Caucasian or Black populations. Physicians should be aware of the risk of hepatoxicity when prescribing oral methimazole to patients of Asian ethnicity.

[Reversible first-degree atrioventricular block due to hyperthyroidism].

PubMed

Çelebi, Aksüyek Savaş; Amasyalı, Basri

2017-04-01

Hyperthyroidism often causes tachyarrhythmia. Reversible atrioventricular block caused by hyperthyroidism is rare occurrence. Presently described is a case of atrioventricular block due to hyperthyroidism and recovery after antithyroid treatment.

Antithyroid drug treatment for graves' disease in children: a long-term retrospective study at a single institution.

PubMed

Ohye, Hidemi; Minagawa, Akinobu; Noh, Jaeduk Yoshimura; Mukasa, Koji; Kunii, Yo; Watanabe, Natsuko; Matsumoto, Masako; Suzuki, Miho; Yoshihara, Ai; Ito, Koichi; Ito, Kunihiko

2014-02-01

The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation. The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients. We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3-18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period. Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3-24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil. Long-term ATD treatment is a useful treatment option for GD in children.

Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine.

PubMed

Boelaert, Kristien; Maisonneuve, Patrick; Torlinska, Barbara; Franklyn, Jayne A

2013-05-01

Hyperthyroidism is common, but opinions regarding optimal therapy with antithyroid drugs or radioiodine (131-I) differ. There are no randomized trials comparing these options in terms of mortality. The aim of the study was to determine whether mortality associated with hyperthyroidism varies with treatment administered or other factors. We conducted a prospective observational population-based study of 1036 subjects aged ≥ 40 years presenting to a single specialist clinic from 1989-2003 with a first episode of hyperthyroidism who were followed until June 2012. Antithyroid drugs or radioiodine (131-I) were administered. We compared causes of death with age-, sex-, and period-specific mortality in England and Wales and used within-cohort analysis of influence of treatment modality, outcome, disease etiology, severity and control, and comorbidities. In 12 868 person-years of follow-up, 334 died vs 290.6 expected (standardized mortality ratio [SMR], 1.15 [95% confidence interval (CI),1.03-1.28]; P = .01). Increased all-cause mortality largely reflected increased circulatory deaths (SMR, 1.20 [95% CI, 1.01-1.43]; P = .04). All-cause mortality was increased for the person-years accumulated during thionamide treatment (SMR, 1.30 [95% CI, 1.05-1.61]; P = .02) and after 131-I not associated with hypothyroidism (SMR, 1.24 [95% CI, 1.04-1.46]; P = .01) but not during T₄ replacement for 131-I-induced hypothyroidism (SMR, 0.98 [95% CI, 0.82-1.18]; P = .85). Within-cohort analysis comparing mortality during thionamide treatment showed a similar hazard ratio (HR) for all-cause mortality when 131-I did not result in hypothyroidism (HR, 0.95 [95% CI, 0.70-1.29]), but reduced mortality with 131-I-induced hypothyroidism (HR, 0.70 [95% CI, 0.51-0.96]). Reduced mortality associated with hypothyroidism was seen only in those without significant comorbidities and not in those with other serious diseases. Atrial fibrillation at presentation (P = .02) and an increment of 10 pmol/L in serial free T₄ concentration during follow-up (P = .009) were independently associated with mortality. Among hyperthyroid subjects aged 40 years or older, mortality was increased during periods of thionamide treatment and after radioiodine not resulting in hypothyroidism, but not during follow-up after radioiodine-induced hypothyroidism. Independent associations of mortality with atrial fibrillation and incomplete biochemical control during treatment indicate potential causative links with poor outcome.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

Antithyroid microsomal antibody

MedlinePlus

... Larsen PR, et al, eds. Williams Textbook of Endocrinology . 12th ed. Philadelphia, PA: Elsevier; 2016:chap 11. ... testing. In: Jameson JL, De Groot LJ, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier ...

Thyroid disorders and the prevalence of antithyroid antibodies in Shiraz population.

PubMed

Karimi, Fariba; Kalantarhormozi, Mohammad Reza; Dabbaghmanesh, Mohammad Hossein; Ranjbar Omrani, Gholamhossein

2014-05-01

Thyroid dysfunction is a common health problem affecting millions of patients worldwide. Autoimmune thyroid disorders are among the most common autoimmune disorders. In this population-based study, we assessed the prevalence of abnormal thyroid function, antithyroid antibodies and the probable relationship between them in Shiraz, southern Iran. Serum thyrotropin (TSH) was determined in 981 subjects (66.8% female and 33.2% male; mean age: 39.1 ± 14.3 years), who were selected with stratified random sampling. Because of the preponderance of females over males, we performed the statistical analyses using sex-weighted data (50% for each sex). Also, antithyroid peroxidase antibodies (TPOAb), and antithyroglobulin antibodies (TgAb) were measured in two random subgroups of 376 and 537 patients respectively). Thyromegaly detected on physical examination. In this cross-sectional study, 8.1% of participants had elevated serum TSH level and 3.4% had low serum TSH level. A statistically significant relationship was found between gender and thyromegaly and TSH values. Positive TPOAb and positive TgAb were detected in 17% and 5.1% of participants respectively. In addition, a significant relationship was observed between elevated TSH levels and positive results for both antibodies. Detectable levels of thyroid antibodies correlated with female sex, while no correlation was observed between detectable levels of thyroid antibodies and thyromegaly. Thyroid disorders, especially elevated TSH level, are common. It seems that autoimmune mechanisms are strongly involved in the etiology of hypothyroidism in this area.

Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

PubMed

Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

2011-01-01

Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

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

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

PubMed

Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

2018-03-09

Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

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.

A follow-up ¹⁸F-FDG brain PET study in a case of Hashimoto's encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis.

PubMed

Pari, Elisa; Rinaldi, Fabrizio; Premi, Enrico; Codella, Maria; Rao, Renata; Paghera, Barbara; Panarotto, Maria Beatrice; De Maria, Giovanni; Padovani, Alessandro

2014-04-01

Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with antithyroid antibodies. It may have an acute onset (episodes of cerebral ischemia, seizure, and psychosis) or it may present as an indolent form (depression, cognitive decline, myoclonus, tremors, and fluctuations in level of consciousness). We here describe a case of encephalopathy presenting as non-convulsive status epilepticus associated with Hashimoto's thyroiditis (HT), unresponsive to corticosteroid therapy, with improvement after plasma exchange treatment. A previously healthy 19-year-old woman, presented generalized tonic-clonic seizures. About a month later, she manifested a speech disorder characterized by difficulties in the production and comprehension of language. Within a few days she also developed confusion and difficulties in recognizing familiar places, with gradual worsening over time. EEG revealed a non-convulsive status epilepticus (NCSE). CSF examination showed slightly elevated cell count and four oligoclonal bands. MRI was unremarkable, and (18)F-FDG brain PET showed widespread hypometabolism, mostly in posterior regions bilaterally. Laboratory and ultrasound findings showed signs of HT. Treatment with steroid was introduced without any improvement. After five sessions of plasma exchange there was a decrease of antithyroid antibodies, as well as EEG and clinical improvement. Three months after discharge (18)F-FDG brain PET showed a complete normalization of the picture, and the patient was asymptomatic. This report emphasizes the successful treatment of HE with plasma exchange in a patient who presented with NCSE. Based on the actual evidence, the term "Encephalopathy associated with Hashimoto's thyroiditis" may be the most proper. Furthermore, to our knowledge, this is the first case of an adult patient studied twice with an (18)F-FDG brain PET: prior to treatment with plasma exchange, and at 3 months follow-up when the patient was clinically completely asymptomatic. Studies in more patients are needed to clarify the relevance of (18)F-FDG brain PET as a possible diagnostic tool for HE.

Comparison of Early Total Thyroidectomy with Antithyroid Treatment in Patients with Moderate-Severe Graves' Orbitopathy: A Randomized Prospective Trial

PubMed Central

Erdoğan, Murat Faik; Demir, Özgür; Ersoy, Reyhan Ünlü; Gül, Kamile; Aydoğan, Berna İmge; Üç, Ziynet Alphan; Mete, Türkan; Ertek, Sibel; Ünlütürk, Uğur; Çakır, Bekir; Aral, Yalçın; Güler, Serdar; Güllü, Sevim; Çorapçıoğlu, Demet; Dağdelen, Selçuk; Erdoğan, Gürbüz

2016-01-01

Background The optimal therapeutic choice for Graves' hyperthyroidism in the presence of moderate-severe Graves' orbitopathy (GO) remains controversial. Objectives We aimed to compare GO course in patients with moderate-severe GO treated with early total thyroidectomy (TTx) versus antithyroid drug (ATD) regimens, in a prospective, randomized manner. Methods Forty-two patients with moderate-severe GO were enrolled. A total of 4.5 g of pulse corticosteroids were given intravenously to all patients before randomization. Patients in the first group were given TTx, whereas patients in the second group were treated with ATDs. TSH was kept between 0.4 and 1 mIU/l. The clinical course of GO was evaluated with proptosis, lid aperture, clinical activity score (CAS), and diplopia. Results Eighteen and 24 patients were randomized to the TTx and ATD groups, respectively. Thyroid autoantibodies decreased significantly, and there were significant improvements in proptosis, lid aperture, and CAS in the TTx group. While in the ATD group the decrement in thyroid autoantibodies was not significant, there were significant improvements in proptosis and CAS. When the TTx group was compared with the ATD group, anti-TPO, anti-Tg, and TSH-receptor antibodies were significantly decreased in the TTx group (p < 0.01), but there was no significant difference with respect to proptosis, lid aperture, CAS, and diplopia between the two groups during a median (min.-max.) follow-up period of 60 months (36-72). Conclusion Although no definitive conclusions could be drawn from the study, mainly due to limited power, early TTx and the ATD treatment regimens, followed by intravenous pulse corticosteroid therapy, seemed to be equally effective on the course of GO in this relatively small group of patients with moderate-severe GO during a median (min.-max.) follow-up period of 60 months (36-72). PMID:27493884

Comparison of Early Total Thyroidectomy with Antithyroid Treatment in Patients with Moderate-Severe Graves' Orbitopathy: A Randomized Prospective Trial.

PubMed

Erdoğan, Murat Faik; Demir, Özgür; Ersoy, Reyhan Ünlü; Gül, Kamile; Aydoğan, Berna İmge; Üç, Ziynet Alphan; Mete, Türkan; Ertek, Sibel; Ünlütürk, Uğur; Çakır, Bekir; Aral, Yalçın; Güler, Serdar; Güllü, Sevim; Çorapçıoğlu, Demet; Dağdelen, Selçuk; Erdoğan, Gürbüz

2016-07-01

The optimal therapeutic choice for Graves' hyperthyroidism in the presence of moderate-severe Graves' orbitopathy (GO) remains controversial. We aimed to compare GO course in patients with moderate-severe GO treated with early total thyroidectomy (TTx) versus antithyroid drug (ATD) regimens, in a prospective, randomized manner. Forty-two patients with moderate-severe GO were enrolled. A total of 4.5 g of pulse corticosteroids were given intravenously to all patients before randomization. Patients in the first group were given TTx, whereas patients in the second group were treated with ATDs. TSH was kept between 0.4 and 1 mIU/l. The clinical course of GO was evaluated with proptosis, lid aperture, clinical activity score (CAS), and diplopia. Eighteen and 24 patients were randomized to the TTx and ATD groups, respectively. Thyroid autoantibodies decreased significantly, and there were significant improvements in proptosis, lid aperture, and CAS in the TTx group. While in the ATD group the decrement in thyroid autoantibodies was not significant, there were significant improvements in proptosis and CAS. When the TTx group was compared with the ATD group, anti-TPO, anti-Tg, and TSH-receptor antibodies were significantly decreased in the TTx group (p < 0.01), but there was no significant difference with respect to proptosis, lid aperture, CAS, and diplopia between the two groups during a median (min.-max.) follow-up period of 60 months (36-72). Although no definitive conclusions could be drawn from the study, mainly due to limited power, early TTx and the ATD treatment regimens, followed by intravenous pulse corticosteroid therapy, seemed to be equally effective on the course of GO in this relatively small group of patients with moderate-severe GO during a median (min.-max.) follow-up period of 60 months (36-72).

The insulin-like growth axis in patients with autoimmune thyrotoxicosis: effect of antithyroid drug treatment.

PubMed

Zimmermann-Belsing, T; Juul, A; Juul Holst, J; Feldt-Rasmussen, U

2004-06-01

Hyperthyroidism is associated with altered growth hormone (GH) secretion. Many patients with thyroid dysfunction experience several poorly described complications such as symptoms and signs also seen in patients with growth hormone deficiency (GHD). We have therefore prospectively evaluated a possible relationship between the thyroid function, body composition, leptin levels and insulin-like growth factor (IGF) related peptides in patients with Graves' disease. DESIGN, PATIENTS, AND MEASUREMENTS: In a prospective group of 24 fasting female patients with Graves' disease (mean age (CI 95%): 40 years (33-47)), we measured serum thyroxine, triiodothyronine, thyrotropine (TSH), TSH receptor antibodies, anti-thyroid peroxidase, leptin, body composition, body mass index (BMI) and IGF-related peptides at diagnosis and after 12 months of treatment with thiamazol (ATD). In thyrotoxic patients IGF-I plus IGF-II correlated positively with IGFBP-3 at baseline (r = 0.90, p < 0.1 x 10(16)) and after 12 months follow-up (r = 0.87, p < 0.1 x 10(-16)). In the thyrotoxic state total IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and acid-labile subunit (ALS) but not free IGF-I decreased significantly from 223 microg/L (189-260) (mean (CI 95%), 877 microg/L (801-953), 4165 microg/L (3772-4577) and 22 mg/L (18-26)) to 198 microg/L (172-226), 788 microg/L (711-865), 3431 microg/L (3135-3741) and 19 mg/L (16-26) (p <0.006), respectively, after 12 months of ATD despite an increase in BMI from 22 (21-23) to 23 kg/m(2) (22-25) (p < 0.0004) but no significant changes in leptin. The complex IGF systems seemed intact in thyrotoxic patients but change in body composition and the regulation of leptin and insulin secretion during treatment of autoimmune thyroid disease influence IGF-related peptides leaving the patient in a state somewhat similar to partial GHD, but the mechanism behind these alterations remains unclear.

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

PubMed

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

2018-02-01

Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction. Here, we compared relationships of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) with various measures of kidney function in euthyroid subjects. Relationships of eGFR, based on creatinine (eGFRcrea), cystatin C (eGFRcysC), creatinine+cystatin C combined (eGFRcrea-cysC) and creatinine clearance (CrCl) with TSH, FT4 and FT3 were determined in 2180 euthyroid subjects (TSH, FT4 and FT3 all within the reference range; anti-thyroid peroxidase autoantibodies negative) who did not use thyroid hormones, anti-thyroid drugs, amiodarone or lithium carbonate. In multivariable models including TSH, FT3 and FT4 together, eGFRcrea, eGFRcysC and eGFRcrea-cysC and CrCl were all positively related to FT3 (P≤0.001), translating into a 2.61 to 2.83mL/min/1.73m 2 increase in eGFR measures and a 3.92mL/min increase in CrCl per 1pmol/L increment in FT3. These relationships with FT3 remained taking account of relevant covariates. In euthyroid subjects renal function is associated with thyroid function status, especially by serum FT3, irrespective of the eGFR equation applied. In the euthyroid state, cystatin C-based eGFR equations are appropriate to assess the relationship of renal function with variation in thyroid function status. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Serum TNF-α in psoriasis after treatment with propylthiouracil, an antithyroid thioureylene

PubMed Central

Elias, Alan N; Nanda, Vanda S; Pandian, Raj

2004-01-01

Background Tumor necrosis factor-α (TNF-α) and its receptors play important roles in the development and persistence of psoriatic plaques. The antithyroid thioureylenes, propylthiouracil and methimazole, are effective in the treatment of patients with psoriasis with a significant number of patients showing clearing or near clearing of their lesions after a several weeks of treatment. Methods The present study examined the effect of treatment with propylthiouracil, given in a dose of 100 mg every 8 hours for 3 months, on the serum levels of TNF-α in 9 patients with plaque psoriasis. Results Propylthiouracil therapy did not result in a significant decline in serum TNF-α concentrations. Conclusions The findings suggest that the therapeutic effect of propylthiouracil in psoriasis appears not to be related to any change in the concentration of TNF-α but occurs via an anti-proliferative mechanism as we have previously speculated. PMID:15119959

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

PubMed

Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma.

PubMed

Yano, Seiichi; Ashida, Kenji; Nagata, Hiromi; Ohe, Kenji; Wada, Naoko; Takeichi, Yukina; Hanada, Yuki; Ibayashi, Yuta; Wang, Lixiang; Sakamoto, Shohei; Sakamoto, Ryuichi; Uchi, Hiroshi; Shiratsuchi, Motoaki; Furue, Masutaka; Nomura, Masatoshi; Ogawa, Yoshihiro

2018-06-08

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85 years; 54% female) were retrospectively analyzed. Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

Prevalence of echocardiographic criteria for the diagnosis of pulmonary hypertension in patients with Graves' disease: before and after antithyroid treatment.

PubMed

Suk, J H; Cho, K I; Lee, S H; Lee, H G; Kim, S M; Kim, T I; Kim, M K; Shong, Y K

2011-09-01

Right-sided heart failure with clinical manifestation is only occasionally seen in patients with Graves' disease (GD). Recent studies revealed that pulmonary hypertension (PHT) detected by echocardiography was not rare in patients with GD. We performed this study to investigate the prevalence of PHT in patients with GD before and after antithyroid treatment, and to assess potential mechanisms from the relationship with clinical and echocardiographic features. Serial echocardiographic examinations were performed in 64 patients with newly diagnosed GD before and after antithyroid treatment to measure cardiac factors, such as pulmonary artery systolic pressure (PAPs), cardiac output, total vascular resistance, left ventricular filling pressure and right ventricular (RV) function. PHT was defined as PAPs of at least 35 mmHg. The prevalence of PHT in untreated GD patients was 44% (28 out of 64 patients). The presence of systemic hypertension was associated with PHT, especially with pulmonary venous hypertension. GD patients with PHT showed reduced RV function represented by higher RV myocardial performance index without difference of pulmonary vascular resistance, RV wall thickness and peak systolic velocity of free wall side of tricuspid annulus. Follow-up echocardiography was performed in 20 out of 28 GD patients with PHT, and PHT disappeared in all except one patient. PHT is a frequent and reversible complication in patients with GD. Our study suggests that PHT in GD may not be related to underlying autoimmune process and increased pulmonary blood flow from thyrotoxicosis might contributes to the pathogenesis of PHT related to GD.

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study.

PubMed

Kobayashi, Tomoko; Iwama, Shintaro; Yasuda, Yoshinori; Okada, Norio; Tsunekawa, Taku; Onoue, Takeshi; Takagi, Hiroshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Goto, Motomitsu; Suga, Hidetaka; Banno, Ryoichi; Yokota, Kenji; Hase, Tetsunari; Morise, Masahiro; Hashimoto, Naozumi; Ando, Masahiko; Kiyoi, Hitoshi; Gotoh, Momokazu; Ando, Yuichi; Akiyama, Masashi; Hasegawa, Yoshinori; Arima, Hiroshi

2018-03-01

Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. This study examined the incidence of endocrine irAEs induced by nivolumab. Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti-thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

Targeting thyroid diseases with TSH receptor analogs.

PubMed

Galofré, Juan C; Chacón, Ana M; Latif, Rauf

2013-12-01

The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Generation of Functional Thyroid Tissue Using 3D-Based Culture of Embryonic Stem Cells.

PubMed

Antonica, Francesco; Kasprzyk, Dominika Figini; Schiavo, Andrea Alex; Romitti, Mírian; Costagliola, Sabine

2017-01-01

During the last decade three-dimensional (3D) cultures of pluripotent stem cells have been intensively used to understand morphogenesis and molecular signaling important for the embryonic development of many tissues. In addition, pluripotent stem cells have been shown to be a valid tool for the in vitro modeling of several congenital or chronic human diseases, opening new possibilities to study their physiopathology without using animal models. Even more interestingly, 3D culture has proved to be a powerful and versatile tool to successfully generate functional tissues ex vivo. Using similar approaches, we here describe a protocol for the generation of functional thyroid tissue using mouse embryonic stem cells and give all the details and references for its characterization and analysis both in vitro and in vivo. This model is a valid approach to study the expression and the function of genes involved in the correct morphogenesis of thyroid gland, to elucidate the mechanisms of production and secretion of thyroid hormones and to test anti-thyroid drugs.

Prevention of Graves' ophthalmopathy.

PubMed

Bartalena, Luigi

2012-06-01

Smoking is the most important risk factor for the occurrence/progression of Graves' ophthalmopathy (GO), as well as for its lower/slower response to immunosuppression. Accordingly, refrain from smoking should be urged, both as primary prevention (removal of risk factors in Graves' patients without GO), secondary prevention (early detection and treatment of asymptomatic/very mild GO) and tertiary prevention (reduction of complications/disability of overt GO). A 6-month course of 200 μg/day sodium selenite can prevent progression of mild GO to more severe GO and is, therefore, a form of secondary prevention and, probably, primary prevention. Correction of thyroid dysfunction and stable maintenance of euthyroidism are important preventive measures. The optimal treatment for hyperthyroidism in patients with GO is uncertain, because evidence demonstrating the superiority of antithyroid drugs over thyroid ablation (radioiodine, thyroidectomy, or both) is lacking. If radioiodine is used, low-dose steroid prophylaxis is recommended, particularly in smokers, to prevent radioiodine-associated GO progression. Copyright © 2011 Elsevier Ltd. All rights reserved.

HASHIMOTO THYROIDITIS AND VESTIBULAR DYSFUNCTION.

PubMed

Chiarella, Giuseppe; Russo, Diego; Monzani, Fabio; Petrolo, Claudio; Fattori, Bruno; Pasqualetti, Giuseppe; Cassandro, Ettore; Costante, Giuseppe

2017-07-01

The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction. We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders. Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV. The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated. AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T 4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

Is antithyroid treatment really relevant for young patients with subclinical hyperthyroidism?

PubMed

Yönem, Ozlem; Dökmetaş, Hatice Sebila; Aslan, Süleyman Murat; Erselcan, Taner

2002-06-01

This study investigated whether symptoms and findings of hyperthyroidism exist in patients with subclinical hyperthyroidism (SCH) and sought to determine whether hyperthyroidism treatment improves them. Twenty patients (mean age: 36.10 +/- 1.41 years) and 20 healthy controls [mean age: 36.35 +/- 1.50 years) were included in the study. The SCH duration of patients was at least 6 months. Bone mineral density (BMD) was measured in both patients and controls. The patients were randomly divided into 2 groups of 10 patients each. Symptoms and findings of hyperthyroidism were evaluated and BMD, 24 hour ambulatory blood pressure, holter measurements and serum lipids were determined initially in both groups and 6 months after the attainment of euthyroidism in the treatment group (Group 1) and after a 6 months follow-up in the observation group (Group 2). In the patient group, BMD showed a decrease of 1.3% and 3.9% in femur neck and L1-4 vertebra compared with controls, respectively. But there was no difference in BMD between patients and controls. Fatigue, nervousness, over sweating, tachycardia and tremor improved with treatment. The number of patients with fatigue, nervousness, over sweating and tachycardia increased in Group 2 after the observation. There was no difference between initial values and after a 6 month period from observation or on attainment of euthyroidism in the values of BMD, lipids, minimal and maximal heart rate, total number of ventricular and supraventricular beats and heart rate variability. As a result symptoms of hyperthyroidism were found to be increased in SCH but they partly decreased after antithyroid treatment. But no favourable effects of antithyroid treatment on BMD, heart rate and arrhythmia incidence were found in young, premenopausal patients with SCH during the 6 month period.

The effect of antithyroid treatment on atrial conduction times in patients with subclinical hyperthyroidism.

PubMed

Nacar, Alper Buğra; Acar, Gürkan; Yorgun, Hikmet; Akçay, Ahmet; Özkaya, Mesut; Canpolat, Uğur; Akkoyun, Murat; Tuncer, Cemal

2012-09-01

Prolonged atrial conduction time measured by tissue Doppler imaging (TDI) has been associated with increased risk of atrial fibrillation. We aimed to evaluate the effect of subclinical hyperthyroidism (SH) and antithyroid treatment on atrial conduction time. A total of 30 patients with SH (26 females; mean age 34.8 ± 8.5 years) and 30 age- and gender-matched controls were included. Using TDI, atrial conduction time was measured from the lateral mitral annulus, septal mitral annulus, and lateral tricuspid annulus. Intra- and interatrial conduction delay were calculated. TDI and thyroid hormone levels were studied at the time of enrollment and after achievement of euthyroid state with propylthiouracil treatment. Patients were followed for 14 ± 3 weeks. Atrial conduction time at the lateral and septal mitral annulus were significantly higher in patients with SH compared to controls. Both inter-, right, and left intraatrial electromechanical delay were prolonged in patients with SH compared to control subjects (21.3 ± 6.1 vs. 13.9 ± 4.3, P < 0.001 and 4.2 ± 3.5 vs. 2.3 ± 1.9, P = 0.014 and 17.1 ± 6.0 vs. 11.6 ± 3.8, P < 0.001, respectively). After achievement of euthyroid state, inter- and left intraatrial electromechanical delay were significantly decreased compared to baseline values and approximated to the values of the control group (P < 0.001). SH is associated with prolonged atrial conduction time. After achievement of euthyroid state, decrement in atrial conduction time may reveal how the antithyroid treatment may prevent the development of atrial fibrillation in these patients. © 2012, Wiley Periodicals, Inc.

Bipolar disorder and antithyroid antibodies: review and case series.

PubMed

Bocchetta, Alberto; Traccis, Francesco; Mosca, Enrica; Serra, Alessandra; Tamburini, Giorgio; Loviselli, Andrea

2016-12-01

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms.

[Conservative treatment of hyperthyroidism (author's transl)].

PubMed

Schumm, P M; Usadel, K H; Schulz, F; Schumann, J; Schöffling, K

1981-01-09

Antithyroid medication was given to 158 patients with hyperthyroidism over a period of 3 to 60 months. After cessation of therapy patients were followed up for 18 to 90 months. Permanent euthyroidism was seen in 70 patients (44.3%) after stopping treatment, however, 88 patients (55.7%) showed recurrence of hyperthyroidism occurring 1 to 56 months after ceasing treatment. In more than 50% recurrence of hyperthyroidism was within the first 3 months and in almost 80% within the first year after end of treatment. There was no connection either between the length of thyrostatic treatment and the recurrence rate or between the length of treatment and recurrence time. Comparison of patients with and without recurrence according to various parameters prior, during and after thyrostatic treatment indicates that there is a high risk of recurrence in patients with 1) nodular and (or) large goitres, 2) marked clinical symptomatology and delayed attainment of a euthyroid state after starting conservative treatment, and 3) the symptom of sweating remaining uninfluenced by antithyroid treatment.

SUBTOTAL THYROIDECTOMY IN THE MANAGEMENT OF GRAVE'S DISEASE.

PubMed

Vincent, P J; Garg, M K; Singh, Y; Bhalla, V P; Datta, S

2001-07-01

Treatment options for Grave's disease include radio-iodine ablation, which is the standard treatment in the USA, antithyroid drug therapy, which is popular in Japan, and surgery, which is commonly employed in Europe and India. There are very few reports about the outcome of surgery in Grave's disease in the Indian setting. Surgery for Grave's disease is an attractive option in under developed countries to cut short prolonged drug treatment, costly follow up and avoid the need for radio-isotope facilities for 1311 ablation. Aim of the present study was to assess the result of subtotal thyroidectomy in 32 cases of Grave's Disease referred for surgery by the endocrinologist in a teaching hospital. Patients were prepared for surgery with Lugol's iodine and propranalol. Subtotal thyroidectomy was performed by a standard technique, which included dissection and exposure of recurrent laryngeal nerves and parathyroid glands. Actual estimation of weight of the remnant gland was not part of the study. Duration of follow up ranged from 6 months to 4 years. 13 of 32 cases were males. Age ranged from 20 to 57 years. There was 1 death in the immediate post-operative period. There were no cases of permanent hypoparathyroidism or recurrent laryngeal nerve palsy. 1 patient developed temporary hypoparathyroidism. 1 patient developed recurrence of hyperthyroidism and 3 cases developed hypothyroidism all within 2 years of surgery. The study has demonstrated the safety and effectiveness of surgery for Grave's Disease in comparison to the reported high incidence of hypothyroidism following radio-iodine therapy and high recurrence rate after anti thyroid drug therapy.

Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options.

PubMed

Bunevicius, Robertas; Prange, Arthur J

2006-01-01

Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.

A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

PubMed

Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

2009-01-01

The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

Prevalence of Thyrotoxicosis, Antithyroid Medication Use, and Complications Among Pregnant Women in the United States

PubMed Central

McNally, Diane L.; Masters, Mary N.; Li, Sue X.; Xu, Yiling; Rivkees, Scott A.

2013-01-01

Background Population-based estimates of the prevalence of thyrotoxicosis (TTX), the frequency of antithyroid drug (ATD) use, and risk of adverse events in pregnant women and their infants are lacking. Therefore, our objective was to obtain epidemiologic estimates of these parameters within a large population-based sample of pregnant women with TTX. Methods A retrospective claims analysis was performed from the MarketScan Commercial Claims and Encounters health insurance database for the period 2005–2009. Women aged 15–44 years, enrolled for at least 2 years, and who had a pregnancy during the study period were included. Diagnosis of TTX was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes using narrow (TTX-1=ICD 242.0) and broad (TTX-2=ICD 242.0 or 242.9) definitions. ATD use was based on prescriptions filled for propylthiouracil (PTU) or methimazole (MMI). Adverse events in mothers and infants were determined from the ICD-9-CM diagnosis codes recorded on submitted claims. Results The database contained 904,497 eligible women. The average yearly prevalence per 1000 pregnant women was 2.46 for TTX-1 and 5.88 for TTX-2. Thirty-nine percent used ATD at any time during the study period. Compared to women without a TTX diagnosis, there was more than a twofold increase for liver disease among women with TTX (odds ratio [OR]=2.08, p<0.001) and a 13% increased risk for congenital anomalies (OR=1.13, p=0.014), but no association was observed with ATD use. The rates of congenital defects (per 1000 infants) associated with ATD use were 55.6 for MMI, 72.1 for PTU, and 65.8 for untreated women with TTX, compared to 58.8 among women without TTX. Conclusions There was some indication of an elevated risk of liver disease and congenital anomalies in women with TTX, but the risk did not appear to be related to the ATD use. There seems to be a higher pregnancy termination rate for women with TTX on MMI, which likely reflects elective pregnancy terminations. PMID:23194469

Radioiodine treatment for pediatric hyperthyroid Grave's disease.

PubMed

Chao, Ma; Jiawei, Xie; Guoming, Wang; Jianbin, Liu; Wanxia, Liu; Driedger, Al; Shuyao, Zuo; Qin, Zhang

2009-10-01

Grave's disease (GD) is an autoimmune disease in which excessive amounts of thyroid hormones circulate in the blood. Treatment for pediatric GD includes (1) antithyroid drugs (ATD), (2) radioiodine, and (3) thyroidectomy. Yet, the optimal therapy remains controversial. We collected studies from all electronically available sources as well as from conferences held in China. All studies using radioiodine and/or ATD and/or thyroidectomy were included. Information was found on 1,874 pediatric GD patients treated with radioiodine, 1,279 patients treated with ATD and 1,362 patients treated surgically. The cure rate for radioiodine was 49.8%; the incidence of hypothyroidism, 37.8%; of relapse, 6.3%; of adverse effects, 1.55%; and of drop outs, 0.6%. These data show that radioiodine treatment is safe and effective in pediatric GD with significant lower incidence of relapse and adverse effects but significantly higher incidence of hypothyroidism as compared with both ATD and thyroidectomy. For the time being, radioiodine treatment for pediatric GD remains an excellent first-line therapy and a good second-line therapy for patients with ATD failure, severe complications, or poor compliance.

Pediatric Graves’ disease: management in the post-propylthiouracil Era

PubMed Central

2014-01-01

The most prevalent cause of thyrotoxicosis in children is Graves’ disease (GD), and remission occurs only in a modest proportion of patients. Thus most pediatric patients with GD will need treatment with radioactive iodine (RAI; 131I) or surgical thyroidectomy. When antithyroid drugs (ATDs) are prescribed, only methimazole (MMI) should be administered, as PTU is associated with an unacceptable risk of severe liver injury. If remission does not occur following ATD therapy, 131I or surgery should be contemplated. When 131I is administered, dosages should be greater than 150 uCi/gm of thyroid tissue, with higher dosages needed for large glands. Considering that there will be low-level whole body radiation exposure associated with 131I, this treatment should be avoided in young children. When surgery is performed near total or total-thyroidectomy is the recommended procedure. Complications for thyroidectomy in children are considerably higher than in adults, thus an experienced thyroid surgeon is needed when children are operated on. Most importantly, the care of children with GD can be complicated and requires physicians with expertise in the area. PMID:25089127

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer.

PubMed

Yu, Hea Min; Park, Soon Hyun; Lee, Jae Min; Park, Kang Seo

2013-09-01

Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.

PubMed

Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp

2017-09-25

Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

Is Traditional Chinese medicine effective for reducing hyperthyroidism?

PubMed

Chang, Cheng-Chieh; Huang, Sheng-Teng

2010-11-01

Graves' disease is an autoimmune disease that can affect a few patients with hyperthyroidism. In this case report, we demonstrated that Traditional Chinese Medicine (TCM) was effective for the patient with hyperthyroidism induced by Graves' disease. The patient also remained in the euthyroid state for several years after the treatment. SUBJECT AND SETTING: A 33-year-old woman had palpitations, fatigability, and weight loss and was diagnosed as having Graves' disease. Urticaria and itching skin appeared after she took an antithyroid drug. Therefore, she sought treatment with TCM. After regular therapy with Jia Wei Xiao Yao San in addition to Xia Ku Cao, Bei Mu, and oyster shell, her symptoms subsided and the thyroid function level returned to normal range with 3 years' treatment. She still remained in the euthyroid state for 3 years after discontinuing the TCM treatment up to the present. Neither complications nor side-effects were noted during the TCM treatment. This case demonstrates that TCM is an effective and alternative option for hyperthyroidism induced by Graves' disease, especially for patients who have an allergic reaction caused by thioamides.

Hyperthyroidism: diagnosis and treatment.

PubMed

Reid, Jeri R; Wheeler, Stephen F

2005-08-15

The proper treatment of hyperthyroidism depends on recognition of the signs and symptoms of the disease and determination of the etiology. The most common cause of hyperthyroidism is Graves' disease. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications. The diagnostic workup begins with a thyroid-stimulating hormone level test. When test results are uncertain, measuring radionuclide uptake helps distinguish among possible causes. When thyroiditis is the cause, symptomatic treatment usually is sufficient because the associated hyperthyroidism is transient. Graves' disease, toxic multinodular goiter, and toxic adenoma can be treated with radioactive iodine, antithyroid drugs, or surgery, but in the United States, radioactive iodine is the treatment of choice in patients without contraindications. Thyroidectomy is an option when other treatments fail or are contraindicated, or when a goiter is causing compressive symptoms. Some new therapies are under investigation. Special treatment consideration must be given to patients who are pregnant or breastfeeding, as well as those with Graves' ophthalmopathy or amiodarone-induced hyperthyroidism. Patients' desires must be considered when deciding on appropriate therapy, and dose monitoring is essential.

[Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case].

PubMed

Hurtado, Claudia; Báez, María Soledad; Bate, Anabel; Opazo, Claudio; Troncoso, Mauricio

2017-05-01

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Radioiodine therapy in elderly patients with subclinical hyperthyroidism due to non-voluminous nodular goiter and its effect on bone metabolism.

PubMed

Rosario, Pedro Weslley

2013-03-01

To evaluate 131I therapy in elderly patients with subclinical hyperthyroidism (SCH) due to nodular disease and who did not receive antithyroid drugs (ATDs), and the effect of the treatment on bone metabolism. Thirty-six patients with TSH ≤ 0.1 mIU/L and non-voluminous goiter (< 60 cm³) were studied. Bone mineral density (BMD) was assessed in 17 women with osteopenia. Mean 24-h 131I uptake was 17.5%. Symptoms of thyrotoxicosis were reported by two (5.5%) patients in the first week after therapy. One year after radioiodine treatment, SCH was resolved in 30 (83.3%) patients, and hypothyroidism was detected in one (2.7%). In the patients in whom TSH returned to normal, femoral and lumbar spine BMD increased by 1.9% and 1.6%, respectively, in average. In elderly patients with SCH and non-voluminous goiter, radioiodine not preceded by ATDs is a safe and effective therapeutic alternative. Resolution of SCH has beneficial effects on BMD in postmenopausal women with osteopenia.

Endocrinology Update: Thyroid Disorders.

PubMed

Kelley, Scott

2016-12-01

Thyroid disease affects nearly every organ system in the body. Hypothyroidism is a state of thyroid hormone insufficiency that results in decreased metabolism and secondary effects including fatigue and weight gain. Primary hypothyroidism typically is a result of autoimmune thyroiditis or iodine deficiency and is assessed by measurement of the thyroid-stimulating hormone (TSH) level. This level usually is elevated in patients with hypothyroidism and low in patients with hyperthyroidism. Levothyroxine is the treatment of choice for hypothyroidism. Hyperthyroidism is a state of thyroid hormone excess, which increases the metabolic rate and causes symptoms including anxiety and tremor. Graves disease is the most common etiology in developed countries. Patients with hyperthyroidism are evaluated with measurement of TSH and free thyroxine levels. Management options include antithyroid drugs, radioactive iodine, and surgery. Thyroid nodules are detected commonly in family medicine, and may or may not be associated with thyroid hormone abnormalities. Patients with thyroid nodules should be evaluated with TSH level measurement and thyroid ultrasonography to guide further testing. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Transient hypothyroidism in the newborn: to treat or not to treat

PubMed Central

Kanike, Neelakanta; Davis, Ajuah

2017-01-01

Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation. PMID:29184815

[Alpha interferon induced hyperthyroidism: a case report and review of the literature].

PubMed

Maiga, I; Valdes-Socin, H; Thiry, A; Delwaide, J; Sidibe, A T; Beckers, A

2015-01-01

Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon.

Maternal hypothyroidism: An overview of current experimental models.

PubMed

Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-10-15

Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

[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.

Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

PubMed

Cesareo, R; Tarabuso, A; Di Benedetto, M; Lacerna, F; Reda, G

2000-03-01

The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

Efficiency analysis of using tailored individual doses of radioiodine and fine tuning using a low-dose antithyroid drug in the treatment of Graves' disease.

PubMed

Liu, Chang-Jiang; Dong, Yan-Yu; Wang, Yi-Wei; Wang, Kai-Hua; Zeng, Qun-Yan

2011-03-01

To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up. In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study. Individual doses of radioiodine, adjusted according to the patient's age, thyroid size, and duration of hyperthyroidism, combined with low-dose ATD for some patients, 1 month or more after radioiodine therapy, was an effective method for treating Graves' disease. Our data showed that using tailored individual doses of radioiodine and fine tuning using low-dose ATD may well be a way to keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine should be decreased a little for small goiter and increased a little for large goiter on the basis of our treatment protocol in future study.

The Prevalence of Antithyroid Autoantibodies in Normal Korean Population*

PubMed Central

Lee, Myung Shik; Lee, Dong Soo; Han, Jin Suk; Cho, Bo Youn; Koh, Chang Soon; Lee, Munho

1986-01-01

The prevalence of antithyroid autoantibodies and the relationship between the presence of autoantibodies and thyroid functions were studied in 848 apparently normal Korean adults with tanned red cell agglutination technique. Results are summarized as follows: 1) The prevalence of antimicrosimal antibody (MCHA) and antithyroglobulin antibody (TGHA) were 4.4% and 1.9% in 458 males, and 12.4% and 5.0% in 390 females, respectively. Both autoantibodies were more prevalent in female (p<0.001, p<0.01). 2) The age-specific prevalence of MCHA was 4.0% in their twenties, 10.1% in their thirties, 12.5% in their forties, 12.0% in their fifties, 8.3% over sixty, and those of TGHA were 2.0% in their twenties, 3.0% in their thirties, 7.0% in their forties, 4.2% in their fifties, 2.5% in subjects over sixty, respectively. Both showed maximal values around forty and fifty and tended to be lower thereafter. 3) Mean T3, T4 and TSH values of high titer group (⩾1:1002) (n=32) were 125 ± 20.6 ng/dl, 9.1 ± 1.7μg/dl and 4.0 ± 1.8 uU/ml, and those of low titer group (<1:1002) (n=44) were 134 ± 24.3 ng/dl, 9.6 ± 1.7 ug/dl and 3.2 ± 1.2 νU/ml. T3 was lower and TSH, higher in high titer group than in low titer group (p<0.05, p<0.05), and no significant difference was observed in T4 level (p<0.1). In conclusion, the prevalence of MCHA and TGHA were higher in apparently normal females than in males with their peaks around forty and fifty, being lower thereafter, and antithyroid autoantibody of high titer (⩾1:1002) was related to alteration of thyroid functions suggesting the existence of “subclinical autoimmune thyroiditis” state. PMID:15759373

The progestin norethisterone affects thyroid hormone-dependent metamorphosis of Xenopus laevis tadpoles at environmentally relevant concentrations.

PubMed

Lorenz, Claudia; Krüger, Angela; Schöning, Viola; Lutz, Ilka

2018-04-15

Previously, levonorgestrel (LNG) has been shown to be an endocrine disruptor of the amphibian thyroid system. In the present study, we investigated whether anti-thyroidal effects are a common property of progestins other than LNG. Premetamorphic Xenopus laevis tadpoles were exposed to norethisterone (NET) and dienogest DIE (each at 0.1-10nM) and LNG (10nM) until completion of metamorphosis. LNG and NET at all concentrations caused a significant developmental retardation whereas DIE did not impair time to metamorphosis. In LNG and 10nM NET exposed animals, tsh mRNA levels increased considerably later than the developmental delay occurred and thyroid histopathology showed no signs of TSH-hyperstimulation. Instead, thyroid glands from these treatments appeared inactive in producing thyroid hormones. Thyroidal transcript levels of dio2 and dio3 were increased by treatments with LNG and NET at 1nM and 10nM, whereas iyd mRNA was reduced by LNG and 10nM NET. Expression of slc5α5 was not changed by any treatment. Effects of DIE differed from those induced by LNG and NET. No developmental delay was measurable; however, tshβ and dio2 mRNAs were increased in pituitary glands of tadpoles exposed to 1.0nM and 10nM DIE. Thyroid histopathology displayed no abnormalities and thyroidal mRNA expression of the genes analyzed (slc5α5, iyd, dio2, dio3) was not changed by DIE. Overall, our results provide evidence that the anti-thyroidal effects already known from LNG are also present in another progestin, namely NET, even at environmentally relevant concentrations. In conclusion we suggest that progestins do not only pose an environmental risk in terms of their impact on reproductive success of aquatic vertebrates, but also with respect to their anti-thyroidal properties affecting amphibian metamorphosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

PubMed Central

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up. PMID:22012048

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin.

PubMed

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.

Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats.

PubMed

Saitoh, M; Umemura, T; Kawasaki, Y; Momma, J; Matsushima, Y; Sakemi, K; Isama, K; Kitajima, S; Ogawa, Y; Hasegawa, R; Suzuki, T; Hayashi, M; Inoue, T; Ohno, Y; Sofuni, T; Kurokawa, Y; Tsuda, M

1999-07-01

2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs in Wistar rats were conducted. The clinical signs of acute oral toxicity were observed including decreased spontaneous movement, a paralytic gait, salivation and lacrimation, and adoption of prone and lateral positions. The LD50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney but not thyroid weights, and serum cholesterol level. The antithyroid toxicity of MMBIs in rats was estimated to be one-tenth that of 2-MBI. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study.

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2010-01-01

sympathomimetic agents, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, COX-2 inhibitors, other non - steroidal anti - inflammatory ...other non - steroidal anti - inflammatory agents, opiate agonists, miscellaneous analgesics and antipyretics, thyroid agents and antithyroid agents. ⁎ p...fold from peak values during occupational PCB use but remain elevated (two-fold) compared to a similar-aged non -occupationally exposed population

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.

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review.

PubMed

Alswat, Khaled A

2015-07-24

Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine.

Hyperthyroidism in pregnancy.

PubMed

Mestman, Jorge H

2012-10-01

Successful outcome in pregnancy hyperthyroidism depends on the cause, interpretation of laboratory tests, and careful use of antithyroid drug (ATD) therapy. Planning of a pregnancy in a woman with active or past history of Graves' hyperthyroidism is mandatory in order to avoid complications. Fetal health may be affected by three factors: poor control of maternal hyperthyroidism, titer of maternal TRAb, and inappropriate use of ATD. Careful assessment of thyroid function through pregnancy and evaluation of fetal development by ultrasonography is the cornerstone for a successful outcome. In a subgroup of women previously treated with ablation therapy, those whose serum TSRAb titers remained elevated, are at risk of having a fetus/neonate with Graves' hyperthyroidism. Use of ATD during lactation is well tolerated, if recommended guidelines are followed. Women during their childbearing age with active Graves' hyperthyroidism should plan their pregnancy. Causes of hyperthyroidism in pregnancy include Graves' disease or autonomous adenoma, and transient gestational thyrotoxicosis as a consequence of excessive production of human chroionic gonadotropin by the placenta. Careful interpretation of thyroid function tests and frequent adjustment of ATD is of utmost importance in the outcome of pregnancy. Graves' hyperthyroidism may relapse early in pregnancy or at the end of the first year postpartum.

Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves' disease.

PubMed

Pichler, R; Maschek, W; Hatzl-Griesenhofer, M; Huber, H; Crespillo-Gómez, C; Berg, J

2003-07-01

Autoimmune thyroid diseases are thought to be mediated by pro-inflammatory cytokines such as TNFalpha and IL-6. Serum levels of cytokines may indicate activity levels of immune functions. We investigated serum levels of IL-6 and of the soluble receptor of TNFalpha in patients with newly diagnosed onset of Graves' hyperthyroidism. The predominantly female group consisted of 39 patients, mean fT4 was 47.6 pg/ml (normal values 7.5=19.0 pg/ml). After diagnosis, all patients were treated with anti-thyroid drugs. Soluble Tumour Necrosis Factor Receptor I (TNF-RI) serum levels were found significantly increased (mean 3.7+/-1.3 ng/ml; p<0,01) compared to a matched group of apparent healthy individuals (mean sTNF-RI 1.8+/-0.5 ng/ml) and to a matched group of patients with treated Graves' disease (mean sTNF-RI 1.9+/-0.6 ng/ml). When IL-6 was assessed only 4 of the 39 patients exhibited increased serum levels. Our finding may indicate that sTNF-RI and possibly its ligand, TNFalpha, could play an important role in the onset of the acute stage of Graves' disease.

[Perioperative and postoperative management of two patients with uncontrolled hyperthyroidism using short acting beta blocker, landiolol].

PubMed

Fujita, Yasuki; Shimizu, Tomoaki; Matsumoto, Atsuhiro; Aoki, Motoaki

2008-09-01

Thyroid storm, sudden onset of life-threatening manifestations of hyperthyroidism, often appears during and after surgery in patients with uncontrolled hyperthyroidism. We report perioperative and postoperative management of two such cases with uncontrolled hyperthyroidism. The first patient is a 41-year-old man with a past history of uncontrolled Graves disease, and was scheduled for emergency video-assisted thoracoscopic surgery for spontaneous pneumothorax. The second patient is a 25-year-old man with a past history of hypertension, and was scheduled for open reduction and internal fixation for mandibular fracture. In both patients, tachycardia and hypertension were observed at admission to the operating room. Therapy included the use of landiolol infusion, a short acting beta blocker, for control of tachycardia. Heart rate was controlled around 90 beats x min(-1) using landiolol during surgery. In each case, landiolol was administered until they can take long acting beta blocker and antithyroid drug orally. In the postoperative period, delirium appeared for a few hours in the first case, but no severe complications were observed in each case. Short acting beta blocker was useful for control of tachycardia in the perioperative and postoperative management of the patient with uncontrolled hyperthyroidism.

Relapse prediction in Graves´ disease: Towards mathematical modeling of clinical, immune and genetic markers.

PubMed

Langenstein, Christoph; Schork, Diana; Badenhoop, Klaus; Herrmann, Eva

2016-12-01

Graves' disease (GD) is an important and prevalent thyroid autoimmune disorder. Standard therapy for GD consists of antithyroid drugs (ATD) with treatment periods of around 12 months but relapse is frequent. Since predictors for relapse are difficult to identify the individual decision making for optimal treatment is often arbitrary. After reviewing the literature on this topic we summarize important factors involved in GD and with respect to their potential for relapse prediction from markers before and after treatment. This information was used to design a mathematical model integrating thyroid hormone parameters, thyroid size, antibody titers and a complex algorithm encompassing genetic predisposition, environmental exposures and current immune activity in order to arrive at a prognostic index for relapse risk after treatment. In the search for a tool to analyze and predict relapse in GD mathematical modeling is a promising approach. In analogy to mathematical modeling approaches in other diseases such as viral infections, we developed a differential equation model on the basis of published clinical trials in patients with GD. Although our model needs further evaluation to be applicable in a clinical context, it provides a perspective for an important contribution to a final statistical prediction model.

Central nervous system vasculitis after starting methimazole in a woman with Graves' disease.

PubMed

Tripodi, Pier Francesco; Ruggeri, Rosaria M; Campennì, Alfredo; Cucinotta, Mariapaola; Mirto, Angela; Lo Gullo, Renato; Baldari, Sergio; Trimarchi, Francesco; Cucinotta, Domenico; Russo, Giuseppina T

2008-09-01

Graves' disease (GD), a prototypical autoimmune disorder, is associated with other autoimmune diseases, including vasculitis. Antithyroid drugs, despite their postulated immunosuppressive effects, may cause several autoimmune disorders. Here we describe the first patient with central nervous system (CNS) vasculitis that developed shortly after the start of methimazole (MMI) treatment for GD. CNS vasculitis was suspected on the basis of the clinical features and neurologic examination, showing a reinforcement of deep reflexes, especially of the left knee and Achilles reflexes. The diagnosis was confirmed by a brain magnetic resonance imaging (MRI), which showed some hyperintensive spots in the subcortical substantia alba and in the parietal area bilaterally, and by a single-photon emission computed tomography (SPECT) imaging, which showed a nonhomogenous distribution of the blood flow in the brain, with a reduced perfusion on the left side of the frontotemporal and parietal regions, and on the right side of the frontotemporal area. MMI was stopped before total thyroidectomy, and symptoms resolved in the next 5 weeks. Six months after MMI was stopped, the brain MRI and SPECT had become normal. To our knowledge, this is the first report of CNS vasculitis related to MMI therapy.

Clinical experience with radioactive iodine in the treatment of childhood and adolescent Graves' disease

PubMed Central

Cury, Adriano N; Meira, Verônica T; Monte, Osmar; Marone, Marília; Scalissi, Nilza M; Kochi, Cristiane; Calliari, Luís E P; Longui, Carlos A

2012-01-01

Background/aims Treatments for Graves' disease (GD) in children and adolescents include oral antithyroid drugs (ATDs), near total thyroidectomy, and radioactive iodine (RAI). ATDs remain the preferred choice in this age group, but because persistent remission occurs in 30% of cases, RAI is becoming a common option for definitive therapy. Methods We performed a review of 65 medical records of GD patients under age 19 years who were followed between 1985 and 2005. Results The prevalence of GD was higher in females (3:1) and during puberty (for both genders). If no remission was detected during ATD treatment, RAI was indicated when the following criteria were present: non-compliance, relapse, or side effects that were related to ATDs, large goiter, and long-term use of ATDs. The majority of patients developed hypothyroidism within 6 months after RAI. A progressive higher dose regimen was implemented in the last 10 years of the study period. A second RAI dose was necessary in eight cases. During the follow-up period, three pregnancies occurred. One patient with a thyroid nodule and benign cytology was detected. Conclusions RAI therapy is effective and safe in the treatment of GD in children and adolescents. PMID:23781316

Reversible dementia with psychosis: Hashimoto's encephalopathy.

PubMed

Mocellin, Ramon; Lubman, Dan I; Lloyd, John; Tomlinson, E Bruce; Velakoulis, Dennis

2006-12-01

A case of presumed Hashimoto's encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.

Serum Levels of Follistatin Are Positively Associated With Serum-Free Thyroxine Levels in Patients With Hyperthyroidism or Euthyroidism

PubMed Central

Tseng, Fen-Yu; Chen, Yen-Ting; Chi, Yu-Chao; Chen, Pei-Lung; Yang, Wei-Shiung

2016-01-01

Abstract Follistatin is a glycoprotein with various biologic functions that plays a role in adipocyte differentiation, muscle stimulation, anti-inflammation, and energy homeostasis. Thyroid hormones influence energy expenditure, glucose, and lipid metabolism. The association between serum follistatin level and thyroid function statuses has seldom been evaluated. The objectives of this study were to compare serum follistatin concentrations in different thyroid function statuses and to evaluate the associations between serum follistatin and free thyroxine (fT4) levels. In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid individuals (EU group) were recruited. The patients of HY group were treated with antithyroid regimens as clinically indicated, whereas no medication was given to EU group. The demographic and anthropometric characteristics, biochemical data, serum levels of follistatin, and thyroid function of both groups at baseline and at the 6th month were compared. Data of all patients were pooled for the analysis of the associations between the levels of follistatin and fT4. At baseline, the HY group had significantly higher serum follistatin levels than the EU group (median [Q1, Q3]: 1.81 [1.33, 2.78] vs 1.13 [0.39, 1.45] ng/mL, P < 0.001). When treated with antithyroid regimens, the follistatin serum levels in HY group decreased to 1.54 [1.00, 1.88] ng/mL at the 6th month. In all patients, the serum levels of follistatin were positively associated with fT4 levels at baseline (β = 0.54, P = 0.005) and at the 6th month (β = 0.59, P < 0.001). The association between follistatin and fT4 levels remained significant in the stepwise multivariate regression analysis, both initially and at the 6th month. In comparison to the EU group, patients with hyperthyroidism had higher serum follistatin levels, which decreased after receiving antithyroid treatment. In addition, the serum follistatin concentrations were positively associated with serum fT4 levels in patients with hyperthyroidism or euthyroidism. PMID:26844494

History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs

PubMed Central

Andrès, Emmanuel; Mourot-Cottet, Rachel; Maloisel, Frédéric; Keller, Olivier; Vogel, Thomas; Séverac, François; Tebacher, Martine; Gottenberg, Jacques-Eric; Weber, Jean-Christophe; Kaltenbach, Georges; Goichot, Bernard; Sibilia, Jean; Korganow, Anne-Sophie; Herbrecht, Raoul

2017-01-01

Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. Patients and methods: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). Results: Mean patient age was 52.2 years old (range: 18–93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0–0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2–21), which was reduced to 0.7 days (range: 2–16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. Conclusions: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of “daily medication” exposure. PMID:28954408

Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study.

PubMed

Dey, D; Kenu, E; Isenberg, D A

2013-08-01

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified.

Managing hyperthyroidism in pregnancy: current perspectives

PubMed Central

Andersen, Stine Linding; Laurberg, Peter

2016-01-01

Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves’ disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6–10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy. PMID:27698567

Managing hyperthyroidism in pregnancy: current perspectives.

PubMed

Andersen, Stine Linding; Laurberg, Peter

2016-01-01

Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves' disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6-10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy.

A stepwise approach to the evaluation and treatment of subclinical hyperthyroidism.

PubMed

Mai, Vinh Q; Burch, Henry B

2012-01-01

To review a stepwise approach to the evaluation and treatment of subclinical hyperthyroidism. English-language articles regarding clinical management of subclinical hyperthyroidism published between 2007 and 2012 were reviewed. Subclinical hyperthyroidism is encountered on a daily basis in clinical practice. When evaluating patients with a suppressed serum thyrotropin value, it is important to exclude other potential etiologies such as overt triiodothyronine toxicosis, drug effect, nonthyroidal illness, and central hypothyroidism. In younger patients with mild thyrotropin suppression, it is acceptable to perform testing again in 3 to 6 months to assess for persistence before performing further diagnostic testing. In older patients or patients with thyrotropin values less than 0.1 mIU/L, diagnostic testing should proceed without delay. Persistence of thyrotropin suppression is more typical of nodular thyroid autonomy, whereas thyroiditis and mild Graves disease frequently resolve spontaneously. The clinical consequences of subclinical hyperthyroidism, such as atrial dysrhythmia, accelerated bone loss, increased fracture rate, and higher rates of cardiovascular mortality, are dependent on age and severity. The decision to treat subclinical hyperthyroidism is directly tied to an assessment of the potential for clinical consequences in untreated disease. Definitive therapy is generally selected for patients with nodular autonomous function, whereas antithyroid drug therapy is more appropriate for mild, persistent Graves disease. The presented stepwise approach to the care of patients presenting with an isolated suppression of serum thyrotropin focuses on the differential diagnosis, a prediction of the likelihood of persistence, an assessment of potential risks posed to the patient, and, finally, a personalized choice of therapy.

Anti-inflammatory effects of methylthiouracil in vitro and in vivo

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

Ku, Sae-Kwang; Baek, Moon-Chang, E-mail: mcbaek@knu.ac.kr; Bae, Jong-Sup, E-mail: baejs@knu.ac.kr

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Here, methylthiouracil (MTU), an antithyroid drug, was examined for its effects on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, human neutrophil adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells and mice. We found that post-treatment with MTU inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. MTU induced potent inhibition of LPS-inducedmore » endothelial cell protein C receptor (EPCR) shedding. It also suppressed LPS-induced hyperpermeability and neutrophil migration in vivo. Furthermore, MTU suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post-treatment with MTU resulted in reduced LPS-induced lethal endotoxemia. These results suggest that MTU exerts anti-inflammatory effects by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. - Highlights: • MTU reduced LPS-mediated hyperpermeability in vitro and in vivo. • MTU inhibited LPS-mediated leukocyte adhesion and migration. • MTU inhibited LPS-mediated production of IL-6 and TNF-α. • MTU reduced LPS-mediated mortality and lung injury.« less

The Effects of Perchlorate on Developing and Adult Birds

DTIC Science & Technology

2003-06-01

Veterinary Medicine at Virginia Tech. Experimental treatment and 3 maintenance during the experiment were done in our animal facilities in the Dept. of...experiments. We have not completed our analysis of these experiments [6]. Reversibility of Perchlorate Effects: In human clinical medicine , where...Ingbar’s The Thyroid, 7th ed., Lippincott-Raven, Philadelphia, PA, USA, pp 296-316. Green WL. 1996. Antithyroid compounds. In Braverman LE, Utiger RD

Comparative study of thyroid hormone and antithyroid antibody levels in patients with gestational diabetes mellitus and pregnant patients with diabetes.

PubMed

Xu, Chengkai; Zhang, Zhenjian

2018-06-01

The aim of this study was to investigate the levels of thyroid hormone and antithyroid antibodies and their relationship with pregnancy outcome in patients with gestational diabetes mellitus (GDM) and diabetic patients. Fifty patients with GDM and 50 pregnant patients with diabetes were selected. Their levels of fasting blood glucose (FBG), glycosylated hemoglobin, FT3, FT4, TGab, TSH, TPOab were measured until parturition. There were no statistically significant differences in the age, gestational age, weight, FBG and glycosylated hemoglobin between the two groups (P>0.05). The levels of FT3 and FT4 in patients with GDM were significantly lower than those in diabetic pregnant patients, while the levels of TSH, TGab, TPOab of GDM patients were significantly higher than in diabetic pregnant patients (P<0.05). The total incidence rates of premature delivery, post-term birth and cesarean section in patients with GDM were significantly higher than those in diabetic pregnant patients. At six-month follow-up, the intellectual levels of infants delivered by patients with GDM were significantly lower than those of diabetic pregnant patients (P<0.05). The levels of thyroid hormones and related antibodies in patients with GDM were abnormal, which may have affected outcome of pregnancy and the intellectual level of their infants.

Hypocalcaemia following thyroidectomy for treatment of Graves' disease: implications for patient management and cost-effectiveness.

PubMed

Hughes, O R; Scott-Coombes, D M

2011-08-01

No consensus exists on optimal treatment for Graves' disease once anti-thyroid medication fails to induce remission. Total thyroidectomy is a more cost-effective treatment than radioactive iodine or life-long anti-thyroid medication, but hypocalcaemia is an important complication, leading to longer hospital admissions and increased prescription costs. This study aimed to compare the relative risk of hypocalcaemia requiring medical treatment for patients with Graves' disease. Prospective cohort study of patients undergoing total thyroidectomy for Graves' disease and for multinodular goitre, calculating serum calcium levels 24-hours post-operatively and prescription rates. Mean corrected calcium concentrations 24 hours post-operatively were 2.05 mmol/l for Graves' disease patients and 2.14 mmol/l for multinodular goitre patients (p = 0.003). Biochemical hypocalcaemia developed in 92 per cent (n = 34) of Graves' disease patients and 71 per cent (n = 43) of multinodular goitre patients (p = 0.012). Graves' disease patients were more likely to be prescribed calcium supplementation pre-discharge (p = 0.037). Total thyroidectomy for Graves' disease carries an increased risk of hypocalcaemia at 24 hours, and of calcium supplementation pre-discharge. Graves' disease patients should be informed of the increased risk of hypocalcaemia associated with total thyroidectomy, and this risk must be factored into future cost-effectiveness analysis.

Amiodarone-induced thyrotoxicosis: A review

PubMed Central

Tsang, Wendy; Houlden, Robyn L

2009-01-01

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) develops in 3% of amiodarone-treated patients in North America. AIT is classified as type 1 or type 2. Type 1 AIT occurs in patients with underlying thyroid pathology such as autonomous nodular goiter or Graves’ disease. Type 2 AIT is a result of amiodarone causing a subacute thyroiditis with release of preformed thyroid hormones into the circulation. OBJECTIVES: To review the literature and present an overview of the differentiation between and management of type 1 and type 2 AIT. METHODS: PubMed, the Cumulative Index to Nursing and Allied Health Literature and Medscape searches of all available English language articles from 1983 to 2006 were performed. Search terms included ‘amiodarone-induced thyrotoxicosis’, ‘complications’, ‘management’, ‘treatment’ and ‘colour flow Dopper sonography’. RESULTS: There is evidence to suggest that to differentiate between type 1 and type 2 AIT, a careful history and physical examination should be performed to identify pre-existing thyroid disease. An iodine-131 uptake test and colour flow Doppler sonography should be performed. Patients with type 2 AIT should receive a trial of glucocorticoids, whereas those with type 1 should receive antithyroid therapy. For patients in whom the mechanism of the thyrotoxicosis is unclear, a combination of prednisone and antithyroid therapy may be considered. PMID:19584973

Investigation on aetiological factors in patients with hyperhidrosis.

PubMed

Akbaş, Ayşe; Kilinç, Fadime

2018-05-07

Hyperhidrosis is a condition where the amount of sweat released to skin surface increases due to the over-active eccrine sweat glands. Hyperhidrosis causes considerable psychosocial distress in affected people. It affects the quality of life and leads to social anxiety disorders. No study has been conducted in our country to investigate the epidemiological, clinical, and laboratory data of patients with hyperhidrosis. In this study, we aimed to retrospectively investigate the clinical and demographic characteristics, causes of sweating and laboratory findings in patients treated for hyperhidrosis at our outpatient clinic and to compare these data with the literature data. A retrospective review was conducted on medical records of patients diagnosed with and treated for hyperhidrosis at outpatient clinic between 2014 and 2017. Adults aged over 18 years were included in study. Age and gender of patients, type and localization of sweating, duration of disease, age of onset of sweating, presence of stress, fever, joint pain and comorbidity, family history, medication use, and examination results were recorded. Records of a total of 70 patients consisting of 30 men and 40 women with hyperhidrosis were examined. Overall mean age was 37.1 years. Mean age was 41 years in women and 32 years in men. Most frequent forms were palmoplantar and axillary hyperhidrosis for primary hyperhidrosis (primary HH), and head-neck and generalized hyperhidrosis for secondary hyperhidrosis (secondary HH). Most common comorbidities were diabetes mellitus, thyroid disease, non-specific joint and bone pain, cardiovascular disease, and neuropsychiatric disease. Cases with secondary HH had a history of drug use (antithyroid drugs, nonsteroidal anti-inflammatory drugs, antidiabetic agents, antidepressants, and antihypertensives). This is the first study that investigated the characteristics of patients with primary and secondary HH in our country. These characteristics can help determine the cause and apply treatment for hyperhidrosis by an appropriate examination and approach.

[Aneurysm of the ascending aorta, hyperthyroidism and pregnancy. Case report].

PubMed

Zavala-Barrios, Berenice; García-Castanedo, Carla; Viruez-Soto, José Antonio; Briones-Garduño, Jesús Carlos; Coronel-Cruz, Fausto

2015-10-01

Aortic aneurysms are a rare condition in childhood and youth, etiology, evolution, natural progression and prognosis in pregnancy unknown. Hyperthyroidism occurs when there is a synthesis and/or excessive secretion of thyroid hormones during pregnancy poses difficulty for diagnosis. The new monitoring hemodynamics in pregnancy by transthoracic bioimpedance is a feasible alternative, noninvasive and real-time hemodynamic monitoring pregnant women. Primiparity 18, is referred to present tachycardia, hyperthyroidism is diagnosed and drug treatment is initiated with antithyroid from week 14.1 echocardiogram reports bivalve aortic aneurysm in the sinus of Valsalva is performed. He was determined to continue the same under strict hemodynamic and fetal monitoring. Pregnancy concludes at the end obtained through the abdomen, at 40.4 weeks, with male product, weight 2250 g, Apgar 9/9, with growth restriction type I. The mother and baby were discharged simultaneously without complications. The hyperdynamic state of pregnant patients in hyperthyroidism and aneurysms is complex and potentially complicable is why the hemodynamic patient monitoring is essential to detect changes in it that endanger the life of the binomial to this condition. Heart disease and hyperthyroidism, in this case, consistent with a fetal complications level is described as intrauterine growth restriction, however narrow and multidisciplinary monitoring and timely interventions binomial lead to satisfactory results in this case.

Preoperative thyroid function and weight loss after bariatric surgery.

PubMed

Neves, João Sérgio; Souteiro, Pedro; Oliveira, Sofia Castro; Pedro, Jorge; Magalhães, Daniela; Guerreiro, Vanessa; Costa, Maria Manuel; Bettencourt-Silva, Rita; Santos, Ana Cristina; Queirós, Joana; Varela, Ana; Freitas, Paula; Carvalho, Davide

2018-05-16

Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded. The preoperative levels of TSH and FT4 were not associated with weight loss after bariatric surgery. The variation of FT3 within the reference range was also not associated with weight loss. In contrast, the subgroup with FT3 above the reference range (12.3% of patients) had a significantly higher excess weight loss than patients with normal FT3. This difference remained significant after adjustment for age, sex, BMI, type of surgery, TSH and FT4. In conclusion, we observed an association between high FT3 and a greater weight loss after bariatric surgery, highlighting a group of patients with an increased benefit from this intervention. Our results also suggest a novel hypothesis: the pharmacological modulation of thyroid function may be a potential therapeutic target in patients undergoing bariatric surgery.

Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves' disease.

PubMed

Dierickx, I; Decallonne, B; Billen, J; Vanhole, C; Lewi, L; De Catte, L; Verhaeghe, J

2014-02-01

Fetal/neonatal hyperthyroidism is a well-known complication of maternal Graves' disease with high concentrations of TSH-receptor antibodies (TRAb). Few data are available on the management of fetal hyperthyroidism in surgically treated Graves' disease. Clinical, ultrasound and biochemical data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10 years before and whose sibling was thin and hyperthyroid at birth. Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was treated through maternal antithyroid drug (ATD) administration; the dose was reduced gradually once fetal tachycardia and valve dysfunction disappeared and normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was maintained. The neonate showed normal growth for GA and T4 concentration at birth but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained strongly suppressed throughout the pre- and postnatal course. Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the severity or duration of the neonatal hyperthyroid flare.

The management of Graves' disease in New Zealand 2014.

PubMed

Cox, Stephanie C; Tamatea, Jade Au; Conaglen, John V; Elston, Marianne S

2016-06-10

Treatment options for Graves' disease (GD), namely anti-thyroid drugs (ATD), surgery or radioiodine (RAI), have not changed over the past two decades. There is no 'gold-standard' treatment for GD. To assess whether the management of GD in New Zealand has changed since the previous 1991 New Zealand survey and compare current management with that of contemporary international studies. We conducted an online survey of New Zealand physicians currently practising internal medicine, diabetes and/or endocrinology, using the cases and questions from the original European and 1991 New Zealand studies. The first-line use of RAI was 5.5%, compared to 41% in the 1991 New Zealand survey. This corresponded to an increase in ATD use, while the rates of surgery as a first-line treatment have remained static over time. New Zealand physicians use technetium scanning for diagnosis, whereas ultrasound and radioiodine uptake were the most commonly selected investigations by European and North American physicians, respectively. The pattern of ATD use in pregnancy was similar to international practice. Treatment of GD in New Zealand has shifted away from the use of RAI as first line treatment. There are significant differences in the investigation and treatment of Grave's disease between New Zealand, Europe and North America.

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

[Thyroid echogeneity as a useful tool for the differential diagnosis of hyperthyroidism in the course of Graves disease and Hashimoto thyroiditis].

PubMed

Niedziela, M; Warzywoda, M; Korman, E

2000-01-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) constitute a spectrum of autoimmune thyroid diseases (AITD). They share an autoimmune pathogenesis, with a cellular and a humoral response to the thyroid gland. As a consequence, dysfunction of the gland itself may develop, characterized by hyperfunction in the case of GD and hypofunction in the case of HT, however at the onset of HT the hyperthyroidism might be observed as a result of a rapid destruction of thyrocytes. An abnormal thyroid echographic pattern characterized by a diffuse low echogeneity has been described in both AITD. This hypoechogeneity is due to three components: increase of intrathyroidal flow, functional changes in thyroid follicles with increased cellularity and decrease of the colloid content, resulting in the reduction of the cell/colloid interface, variable degree of lymphocytic infiltration. The first two components may be reversible during medical treatment and seem to be characteristic for GD, whereas lymphocytic infiltration may rather represent mostly HT. Here we present a 17-year-old girl with typical clinical signs of hyperthyroidism [firm goiter (II degrees), tachycardia, palpitations, nervousness, excessive sweating and tremor]. Laboratory tests were the following: fT3 - 6.59 pg/ml(increasing), fT4 - 1.99 ng/dl(increasing), TSH - 0.02 micro IU/ml(decreasing); anti-Tg-Ab - 840 IU/ml(increasing), anti-TPO-Ab - 190 IU/ml(increasing) (4 months later antithyroid antibodies were 2200 and 70, respectively). Ultrasound examination showed hypoechogeneity of the whole gland and enhanced vascular flow based on power Doppler analysis. Thyroid scan visualized the generally increased uptake of technetium. The girl was put on beta-blocker (propranolol) and later an antithyroid drug (thiamazole) was added. A course of disease was unstable, therefore the fine-needle aspiration biopsy was performed and showed the presence of single groups of normal thyrocytes and scanty colloid with no features of HT. Power Doppler analysis showed still enhanced blood flow within a gland inspite of euthyroid state. After a very unsteady period of the disease, the euthyroid state is maintained although the medical treatment was given up. The full recovery of normal blood flow and normal echogeneity of the thyroid was documented. The latter supports the diagnosis of GD. Follow-up of the thyroid echogeneity is of great diagnostic and prognostic value if the assay of TSHR-Ab is not available. On the other side, it has to be remembered that TSHR-Ab do not have to be positive in patients with GD and can be positive in patients with HT.

Cancer complicating systemic lupus erythematosus – a dichotomy emerging from a nested case-control study

PubMed Central

Kenu, E; Isenberg, DA

2013-01-01

Objectives We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. Methods We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Results Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52–1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). Conclusion We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified. PMID:23857987

Metabolic Profiling Provides a System Understanding of Hypothyroidism in Rats and Its Application

PubMed Central

Dong, Xin; Zhu, Zhenyu; Li, Wuhong; Lou, Ziyang; Chai, Yifeng

2013-01-01

Background Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components. Methodology/Principal Findings A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism) were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways. Conclusions/Significance Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on hypothyroidism. PMID:23409005

Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

PubMed Central

Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio

2017-01-01

Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal function. PMID:28713331

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

PubMed

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

1993-01-20

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

[Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].

PubMed

Ivović, Miomira; Radiojković, Biljena; Penezić, Zorana; Stojković, Mirjana; Tancić, Milina; Vujović, Svetlana; Bogdanović, Andrija; Drezgić, Milka

2003-01-01

Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyroidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyroid state is established [3]. Three treatment modalities are available in hyperthyroidism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranulocytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase, lactic dehydrogenase and mildly elevated aspartate transminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1-1% patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after session of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1-5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6, 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Erosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications, life-threatening agranulocytosis and acute coronary syndrome.

Propylthiouracil, independent of its antithyroid effect, promotes vascular smooth muscle cells differentiation via PTEN induction.

PubMed

Chen, Wei-Jan; Pang, Jong-Hwei S; Lin, Kwang-Huei; Lee, Dany-Young; Hsu, Lung-An; Kuo, Chi-Tai

2010-01-01

Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have an antiatherosclerotic effect. The aim of this study is to determine the impact of PTU on phenotypic modulation of vascular smooth muscle cells (VSMCs), as phenotypic modulation may contribute to the growth of atherosclerotic lesions and neointimal formation after arterial injury. Propylthiouracil reduced neointimal formation in balloon-injured rat carotid arteries. In vitro, PTU may convert VSMCs from a serum-induced dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morphology and an increase in the expression of SMC differentiation marker contractile proteins, including calponin and smooth muscle (SM)-myosin heavy chain (SM-MHC). Transient transfection studies in VSMCs demonstrated that PTU induced the activity of SMC marker genes (calponin and SM-MHC) promoters, indicating that PTU up-regulates these genes expression predominantly at the transcriptional level. Furthermore, PTU enhanced the expression of PTEN and inhibition of PTEN by siRNA knockdown blocked PTU-induced activation of contractile proteins expression and promoter activity. In the rat carotid injury model, PTU reversed the down-regulation of contractile proteins and up-regulated PTEN in the neointima induced by balloon injury. Propylthiouracil promotes VSMC differentiation, at lest in part, via induction of the PTEN-mediated pathway. These findings suggest a possible mechanism by which PTU may contribute to its beneficial effects on atherogenesis and neointimal formation after arterial injury.

Is dietary nitrate/nitrite exposure a risk factor for development of thyroid abnormality? A systematic review and meta-analysis.

PubMed

Bahadoran, Zahra; Mirmiran, Parvin; Ghasemi, Asghar; Kabir, Ali; Azizi, Fereidoun; Hadaegh, Farzad

2015-05-01

The potential effects of inorganic nitrate/nitrite on global health are a much debated issue. In addition to possible methemoglobinemia and carcinogenic properties, anti-thyroid effects of nitrate/nitrite have been suggested. Considering the growing significance of nitrate/nitrite and since there is no comprehensive review in data available, clarifying the effect of nitrate/nitrite on thyroid disorder outcomes is essential. Therefore, we conducted this systematic review of experimental and clinical studies, and a meta-analysis of relevant cohort and cross-sectional studies investigating the association of nitrate/nitrite exposure and thyroid function. Most animal studies show that high exposure (~10-600 times of acceptable daily intake) to nitrate/nitrite induces anti-thyroid effects, including decreased serum level of thyroid hormones and histomorphological changes in thyroid gland; however no similar observations have been documented in humans. Based on our meta-analysis, no significant association was observed between nitrate exposure and the risk of thyroid cancer, hyper- and hypothyroidism; findings from three cohort studies however showed a significant association between higher exposure to nitrite and the risk of thyroid cancer (risk = 1.48, 95% confidence interval = 1.09-2.02, P = 0.012). Additional research is needed to clarify the association between nitrate/nitrite exposures and both thyroid function and cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

The relationship between procalcitonin and thyroid autoantibodies in patients with autoimmune thyroiditis.

PubMed

Oncul, Ali; Ates, Ihsan; Arikan, Mehmet Fettah; Yilmaz, Nisbet; Topcuoglu, Canan; Yilmaz, Fatma Meric; Altay, Mustafa

2017-11-01

The aim of this study is to investigate the serum levels of procalcitonin and its association with autoantibodies in patients with euthyroid Hashimoto's thyroiditis. A total of 80 participants were included in the study; 40 of which were newly diagnosed with Hashimoto's thyroiditis, aged over 18, and 40 of which were healthy volunteers. The serum levels of procalcitonin were measured by enzyme-linked immunosorbent assay kit. Thyroid function tests were analyzed in hormone laboratory with Electro-chemiluminescence immunoassay. Hashimoto's thyroiditis patients had higher median procalcitonin levels than those of the control group (34.3 pg/mL vs 27.8 pg/mL respectively; P=.037). Also, male patients had higher median procalcitonin levels as compared to female patients (37 pg/mL vs 27 pg/mL respectively; P=.013). In the Hashimoto's thyroiditis group, procalcitonin level was positively correlated with anti-thyroglobulin and anti-thyroid peroxidase levels (r=.559, P<.001; r=634, P<.001, respectively). The procalcitonin and anti-thyroid peroxidase levels were identified to be an independent predictor in diagnosis of Hashimoto's thyroiditis. The fact that procalcitonin was found to be correlated with thyroid autoantibodies and found to be an independent risk factor for Hashimoto's thyroiditis in the regression analysis in the framework of this study urges us to think that procalcitonin may be associated with the autoimmunity. © 2017 Wiley Periodicals, Inc.

Serum levels of IgG and IgG4 in Hashimoto thyroiditis.

PubMed

Kawashima, Sachiko-Tsukamoto; Tagami, Tetsuya; Nakao, Kanako; Nanba, Kazutaka; Tamanaha, Tamiko; Usui, Takeshi; Naruse, Mitsuhide; Minamiguchi, Sachiko; Mori, Yusuke; Tsuji, Jun; Tanaka, Issei; Shimatsu, Akira

2014-03-01

Although IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and lymphocytes of various organs, the details of this systemic disease are still unclear. We screened serum total IgG levels in the patients with Hashimoto thyroiditis (HT) to illustrate the prevalence of IgG4-related thyroiditis in HT. Twenty-four of 94 patients with HT (25.5%) had elevated serum IgG levels and their serum IgG4 was measured. Five of the 24 cases had more than 135 mg/dL of IgG4, which is the serum criterion of IgG4-related disease. One was a female patient who was initially treated as Graves' disease and rapidly developed a firm goiter and hypothyroidism. The biopsy of her thyroid gland revealed that follicular cells were atrophic with squamous metaplasia, replaced with fibrosis, which was compatible with the fibrous variant of HT. Immunohistochemical examination revealed diffuse infiltration of IgG4-positive plasma cells, and the serum IgG4 level was 179 mg/dL. The levels of IgG and IgG4 were positively correlated with the titers of anti-thyroglobulin antibody or anti-thyroid peroxidase antibody. In conclusion, at least a small portion of patients with HT with high titers of anti-thyroid antibodies may overlap the IgG4-related thyroiditis.

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review

PubMed Central

Alswat, Khaled A.

2015-01-01

Patient: Female, 52 Final Diagnosis: Refractory iodine induced hyperthyroidism Symptoms: Neck swelling • shortness of breath Medication: Cholestyramine Clinical Procedure: Total thyroidectomy Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. Case Report: A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Conclusions: Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine. PMID:26207323

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.

Neonatal thyrotoxicosis presenting as persistent pulmonary hypertension

PubMed Central

Obeid, Rawad; Kalra, Vaneet Kumar; Arora, Prem; Quist, Felix; Moltz, Kathleen C; Chouthai, Nitin Shashikant

2012-01-01

Neonatal hyperthyroidism is a rare condition caused either by transplacental passage of thyroid-stimulating immunoglobulins from a mother with Graves’ disease or by activating mutations of the thyrotropin receptors and α-subunit of G-protein. The clinical features may vary. We report a case of neonatal thyrotoxicosis in an infant born to a mother with Graves’ disease, who presented with cardiorespiratory failure and persistent pulmonary hypertension (PPHN). PPHN resolved with specific antithyroid treatment and extracorporeal membrane oxygenation was not required. PMID:22669869

[Congenital hyperthyroidism in maternal Basedow disease].

PubMed

Meden, H; Rath, W

1989-09-01

A case of congenital hyperthyroidism, after pregnancy complicated by Graves' disease is presented. Fetal tachycardia was the cardial symptom. Caesarean section was performed in the 29 years old patient with normal thyroid function in the 29th week of pregnancy. The neonate showed symptoms of a congenital hyperthyroidism with goitre. Antithyroid antibodies were found in the serum of both mother and child. At the age of ten weeks, after a short course of thyrostatic treatment, the infant was discharged with normal thyroid function following complicationfree progress.

Incidence of hypothyroidism occurring long after iodine-131 therapy for hyperthyroidism

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

Holm, L.E.; Lundell, G.; Israelsson, A.

1982-02-01

We have studied the long-term incidence of hypothyroidism in 4,473 formerly hyperthyroid patients given I-131 therapy between 1951 and 1975. The mean age at the first I-131 treatment was 56 yr. Six percent developed hypothyroidism within one year of therapy, and 72% within 26 yr. Prior antithyroid medication did not affect the incidence of hypothyroidism. Patients cured with one dose of I-131 had a lower cumulative long-term incidence of hypothyroidism than those requiring more than one dose.

Male sex, African American race or ethnicity, and triiodothyronine levels at diagnosis predict weight gain after antithyroid medication and radioiodine therapy for hyperthyroidism.

PubMed

Ariza, Miguel A; Loken, Won Mee J; Pearce, Elizabeth N; Safer, Joshua D

2010-01-01

To determine whether racial or ethnic differences affect weight gain after treatment of hyperthyroidism and to reassess established risk factors such as sex, age, and cause of hyperthyroidism. We conducted a retrospective review of medical records of 111 patients treated with radioiodine (RAI) for hyperthyroidism, with or without preceding antithyroid medication, during 2002 to 2005. We ascertained age, sex, race or ethnicity, insurance status, compliance with visits, serum triiodothyronine (T3) level at diagnosis, and cause of hyperthyroidism. Weights and serum thyroidstimulating hormone levels were obtained at diagnosis, at time of RAI therapy, and at 0 to 4 months, 4 to 8 months, 8 to 12 months, and 24 months after RAI treatment. There was a significant weight increase after treatment of hyperthyroidism. Levels of T3 at initial diagnosis of hyperthyroidism, male sex, and black or Hispanic ethnicity were found to be independent predictors of weight gain after RAI treatment. We found a significant interaction between race or ethnicity and sex in multivariate models. There was no difference in thyroid function across racial or ethnic groups or the sexes. Age, cause of hyperthyroidism, posttreatment thyroid-stimulating hormone level, compliance, and insurance status were not found to be significant predictors of weight gain. The T3 level at the time of diagnosis of hyperthyroidism is a strong predictor of weight gain after treatment of hyperthyroidism. Black race or ethnicity and male sex are also risk factors for weight gain.

Epidemiology of endemic goitre in western Colombia

PubMed Central

Gaitan, E.; Merino, H.; Rodriguez, G.; Medina, P.; Meyer, J. D.; DeRouen, T. A.; MacLennan, R.

1978-01-01

This paper reports on recent epidemiological observations in western Colombia, which further demonstrate the presence of naturally-occurring goitrogens contaminating water supplies in areas where goitre persists despite prolonged and continuous iodine supplementation. 'Prospective' and 'cross-sectional' studies in 41 localities where the populations have been on a uniform and adequate iodine supplementation for the last 10-20 years indicate that, in the endemia of western Colombia, environmental factors other than nutritional iodine deficiency are responsible for differences in goitre prevalence. Further epidemiological studies to determine the causal factors for the persistence of the endemia established a correlation between the sources of drinking water and goitre prevalence rates. Organic compounds containing sulfur with marked thionamide-like antithyroid activity were isolated from water supplying endemic goitre districts, and results are presented supporting the hypothesis that sedimentary rocks rich in organic matter are the main source of water-borne goitrogens. Bacteriological investigations showed that the presence of Klebsiella pneumoniae in drinking water and bacterial concentration were related significantly with goitre prevalence only in the presence of other variables, particularly the presence of sedimentary rocks. In the light of these epidemiological observations and experimental studies it may be concluded that, at present, endemic goitre in western Colombia is not due to nutritional iodine deficiency, but that water supplies are contaminated with sulfur-bearing organic compounds with thionamide-like antithyroid activity most probably deriving from sedimentary rocks rich in organic matter and that these compounds are the main factor underlying the endemia. PMID:80287

Usefulness of thyrogastric immune features as predictors of pernicious anaemia that lacks intrinsic factor antibody.

PubMed

Chan, J; Chan, H Y F

2011-08-01

The study aims to evaluate the diagnostic utility of thyrogastric immune features in the identification of intrinsic factor antibody negative (IFA -ve) pernicious anaemia (PA) patients. Clinico-pathological features of 'intrinsic factor antibody positive (IFA +ve) PA' and 'IFA -ve presumed PA' Chinese patients in a single hospital (2001-2009) were studied. Coefficients of independent variables identified were used as weighted scores. The result was validated by patients (1994-2000) with Schilling test done. Comparison of 127 'IFA +ve PA' and 130 'IFA -ve presumed PA' patients showed four independent variables, namely (+) gastric parietal cell (GPC) antibody (OR, 2.907, 95%; CI, 2.346-3.468; P < 0.001), (+) antithyroid antibodies (OR, 3.098, 95%; CI, 2.496-3.70; P < 0.001), (+) gastric atrophy (OR, 3.827, 95%; CI, 3.041-4.64; P = 0.001), and (-) Helicobacter pylori (HP) organisms (OR, 0.134, 95%; CI, -1.60-1.869; P = 0.023). The respective scores were 1.067, 1.131, 1.342 and -2.012. Total scores for each patient ranged from 3.54 to -2.012. When the cut-off score 1.528 was applied to the validation sample (n = 75), the specificity of identifying IFA -ve PA was 100%, sensitivity 53%, positive predictive value 100%, and negative predictive value 36%. Patients with two out of three features, GPC, antithyroid antibodies, gastric atrophy, but without HP organisms; or three features with HP organisms, can be predicted to have PA. © 2011 Blackwell Publishing Ltd.

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.

Regression of Ophthalmopathic Exophthalmos in Graves' Disease After Total Thyroidectomy: a Prospective Study of a Surgical Series.

PubMed

Bhargav, P R K; Sabaretnam, M; Kumar, S Chandra; Zwalitha, S; Devi, N Vimala

2017-12-01

Autoimmune ophthalmopathy is one of the salient clinical features associated with Graves' disease. Exophthalmos is one of the commonest manifestations of Graves' associated ophthalmopathy. It is reported to regress after thyroidectomy favourably compared to radioiodine or antithyroid drug therapy. In this context, we present our experience based on a surgical series of Graves' disease. This is a prospective study of 15 patients of Graves' disease associated with ophthalmopathic exophthalmos. Preoperative and monthly postoperative evaluation of exophthalmos was done with Hertel's exophthalmometer, apart from documenting lid, extra-ocular muscle and orbital involvement. The minimum follow-up of the cohort was 12 months. The female to male ratio was 12:3 and the mean age of the subjects was 33.4 years (18-55). Exophthalmos was bilateral in 13 and unilateral in 2 patients. All the 15 patients underwent total thyroidectomy without any major morbidity. Exophthalmos regressed in 12 patients at a mean follow-up of 15.6 ± 6.4 months (14-38) and was static in 3. None of the cases had worsened ophthalmopathy at the final follow-up. Mean regression of exophthalmos was 2.1 mm (1-5). The regression was statistically significant at P value = 0.035. Surgery has a positive impact on the regression of ophthalmopathic exophthalmos associated with Graves' disease.

[Hyperthyroidism in the elderly: aspecific signs may cause a delay in diagnosis].

PubMed

Rozendaal, F P

2005-05-01

The clinical manifestations of thyroid diseases in the elderly are often atypical and can easily be attributed to other medical conditions or 'normal aging'. Two nursing home patients with hyperthyroidism are described. Due to the atypical presentation of the thyroid disease their complaints were attributed to other conditions. In both patients there was a significant delay in diagnosis and treatment of hyperthyroidism. In elder patients signs and symptoms of thyreotoxicosis are frequently related to cardiovascular, gastrointestinal and neuropsychiatric disorders. Most often occur atrial fibrillation, worsening of cardiac failure and angina pectoris, weight loss, anorexia, constipation, cognitive impairment and delirium. Delay of diagnosis and treatment of hyperthyroidism may be potentially harmful to the patient. Untreated thyreotoxicosis may lead to serious cardiovasculair complications (particularly cardiac failure and cerebrovascular accidents), mental deterioration and osteoporosis. In elder people with unexplained and vague signs and symptoms thyroid function should always be checked. The TSH assay is a very accurate diagnostic test for screening thyroid function. A normal TSH indicates euthyroidism with an accuracy of almost 100%. The medical treatment for hyperthyreoidism in the elderly are antithyroid drugs. When an euthyroid state is rendered, suppletion with L-thyroxine may be nessecary. Radioactive iodine treatment is preferred in some cases though there may be practical difficulties with the application of this treatment in nursing home patients because temporary isolation is necessary.

Prospective study of the changes in thyrotropin binding inhibitory immunoglobulins in Graves' disease treated by subtotal thyroidectomy or radioactive iodine

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

Teng, C.S.; Yeung, R.T.T.; Khoo, R.K.K.

1980-06-01

The effects of subtotal thyroidectomy and radioactive iodine on thyroid-stimulating immunoglobulins, as measured by a receptor assay, more appropriately termed TSH binding inhibitory immunoglobulins (TBII), were studied in 74 patients with Graves' disease. Fourty-four patients received radioactive iodine therapy, while 30 were subjected to subtotal thyroidectomy. After radioactive iodine, more patients were TBII-positive (90.5% vs 81.8%) than before treatment, and the mean TBII index decreased dramatically, the maximum decrease being 3 months. The mean TBI index subsequently returned gradually to the pretreatment level. Subtotal thyroidectomy had a different effect on TBII activity. TBII indices were positive in 89.3% of thesemore » patients before any treatment but were positive in only 40% (12 patients) after antithyroid drugs had been given before surgery. After surgery, TBII indices remained positive in 7 patients, while the remaining 5 patients became TBII negative. Seventeen patients (56.7%) were TBII negative before operation and remained so after surgery. One patient who was TBII negative before operation became TBII positive 2 months after operation. Interestingly, postoperative relapse of hyperthyroidism occurred in 3 patients who were TIBII positive, while hypothyroidism occurred in patients who were TBII negative. Thus, the TBII activity after subtotal thyroidectomy might be an important factor in determining the outcome of surgery.« less

Which sources of flavonoids: complex diets or dietary supplements?

PubMed

Egert, Sarah; Rimbach, Gerald

2011-01-01

There is increasing interest in the potential health benefits of dietary flavonoids. Fruits and vegetables, tea, and cocoa are rich natural sources of flavonoids. Epidemiological studies have indicated that consumption of these foods is likely to be associated with a reduced risk of cardiovascular disease, but the etiology of this benefit is not yet clearly defined. Furthermore, in some acute interventions, a positive effect of tea and cocoa on vascular function has been reported. An alternative source of flavonoids is dietary supplements, which have become increasingly popular in the recent past. In this context, it needs to be critically evaluated whether vascular health-promoting and other positive properties of flavonoid-rich diets can be replaced by purified flavonoids as dietary supplements. Plant sources of flavonoids contain a complex mixture of secondary plant metabolites and not only flavonoids per se. This complex mixture of secondary plant metabolites cannot be simply exchanged by single purified compounds as dietary supplements. If flavonoids are given as dietary supplements, toxicity issues as well as nutrient drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities. In this review article, the available literature on the safety issues surrounding high dose supplemental flavonoid consumption has been summarized.

[Thyroid emergencies : Thyroid storm and myxedema coma].

PubMed

Spitzweg, C; Reincke, M; Gärtner, R

2017-10-01

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

Radioactive iodine therapy in cats with hyperthyroidism

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

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

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

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.

Unusual Synchronous Methimazole-Induced Agranulocytosis and Severe Hepatotoxicity in Patient with Hyperthyroidism: A Case Report and Review of the Literature

PubMed Central

Yang, Jun; Zhang, Jun; Xu, Qin; Sheng, Guo-ping; Weng, Wan-wen; Dong, Meng-jie

2015-01-01

Context. To report a patient with hyperthyroidism who developed concurrent occurrence of agranulocytosis and severe hepatotoxicity after taking methimazole (MMI). Case. A 51-year-old Chinese male was diagnosed as hyperthyroidism with normal white blood count and liver function. After 4 weeks' treatment with MMI 20 mg/d, it developed to agranulocytosis and severe cholestatic hepatotoxicity. The patient's symptoms and laboratory abnormalities disappeared after the withdrawal of MMI; his white blood count and liver function recover to normal in 2 weeks and 5 weeks, respectively. 296 MBq dose of 131I was given to the patient 3 weeks after the withdrawal of MMI and his thyroid function was back to normal in 6 months. As we know through literature review, only 5 previous cases reported the synchronous ATD-induced agranulocytosis and severe hepatotoxicity in patients with hyperthyroidism. Methods. Review of the patient's clinical course. Literature review of cases of hyperthyroidism with agranulocytosis and severe hepatotoxicity demonstrated that these complications occurred after taking antithyroid drug (ATD). Conclusions. Patient with hyperthyroidism can have synchronous ATD-induced agranulocytosis and severe hepatotoxicity. This case is extremely rare, but the adverse effects with ATDs is clinically significant. The clinicians need to be careful about this and monitor biochemical of patients who take ATDs. PMID:26060496

Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan.

PubMed

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2016-02-01

Thyroid storm is a life-threatening and emergent manifestation of thyrotoxicosis. However, predictive features associated with fatal outcomes in this crisis have not been clearly defined because of its rarity. The objective of this study was to investigate the associations of patient characteristics, treatments, and comorbidities with in-hospital mortality. We conducted a retrospective observational study of patients diagnosed with thyroid storm using a national inpatient database in Japan from April 1, 2011 to March 31, 2014. Of approximately 21 million inpatients in the database, we identified 1324 patients diagnosed with thyroid storm. The mean (standard deviation) age was 47 (18) years, and 943 (71.3%) patients were female. The overall in-hospital mortality was 10.1%. The number of patients was highest in the summer season. The most common comorbidity at admission was cardiovascular diseases (46.6%). Multivariable logistic regression analyses showed that higher mortality was significantly associated with older age (≥60 years), central nervous system dysfunction at admission, nonuse of antithyroid drugs and β-blockade, and requirement for mechanical ventilation and therapeutic plasma exchange combined with hemodialysis. The present study identified clinical features associated with mortality of thyroid storm using large-scale data. Physicians should pay special attention to older patients with thyrotoxicosis and coexisting central nervous system dysfunction. Future prospective studies are needed to clarify treatment options that could improve the survival outcomes of thyroid storm.

Factors Associated With Mortality of Thyroid Storm

PubMed Central

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2016-01-01

Abstract Thyroid storm is a life-threatening and emergent manifestation of thyrotoxicosis. However, predictive features associated with fatal outcomes in this crisis have not been clearly defined because of its rarity. The objective of this study was to investigate the associations of patient characteristics, treatments, and comorbidities with in-hospital mortality. We conducted a retrospective observational study of patients diagnosed with thyroid storm using a national inpatient database in Japan from April 1, 2011 to March 31, 2014. Of approximately 21 million inpatients in the database, we identified 1324 patients diagnosed with thyroid storm. The mean (standard deviation) age was 47 (18) years, and 943 (71.3%) patients were female. The overall in-hospital mortality was 10.1%. The number of patients was highest in the summer season. The most common comorbidity at admission was cardiovascular diseases (46.6%). Multivariable logistic regression analyses showed that higher mortality was significantly associated with older age (≥60 years), central nervous system dysfunction at admission, nonuse of antithyroid drugs and β-blockade, and requirement for mechanical ventilation and therapeutic plasma exchange combined with hemodialysis. The present study identified clinical features associated with mortality of thyroid storm using large-scale data. Physicians should pay special attention to older patients with thyrotoxicosis and coexisting central nervous system dysfunction. Future prospective studies are needed to clarify treatment options that could improve the survival outcomes of thyroid storm. PMID:26886648

Which Sources of Flavonoids: Complex Diets or Dietary Supplements?1

PubMed Central

Egert, Sarah; Rimbach, Gerald

2011-01-01

There is increasing interest in the potential health benefits of dietary flavonoids. Fruits and vegetables, tea, and cocoa are rich natural sources of flavonoids. Epidemiological studies have indicated that consumption of these foods is likely to be associated with a reduced risk of cardiovascular disease, but the etiology of this benefit is not yet clearly defined. Furthermore, in some acute interventions, a positive effect of tea and cocoa on vascular function has been reported. An alternative source of flavonoids is dietary supplements, which have become increasingly popular in the recent past. In this context, it needs to be critically evaluated whether vascular health-promoting and other positive properties of flavonoid-rich diets can be replaced by purified flavonoids as dietary supplements. Plant sources of flavonoids contain a complex mixture of secondary plant metabolites and not only flavonoids per se. This complex mixture of secondary plant metabolites cannot be simply exchanged by single purified compounds as dietary supplements. If flavonoids are given as dietary supplements, toxicity issues as well as nutrient drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities. In this review article, the available literature on the safety issues surrounding high dose supplemental flavonoid consumption has been summarized. PMID:22211185

Guidelines for the use of radioiodine in the management of hyperthyroidism: a summary. Prepared by the Radioiodine Audit Subcommittee of the Royal College of Physicians Committee on Diabetes and Endocrinology, and the Research Unit of the Royal College of Physicians.

PubMed

Lazarus, J H

1995-01-01

Radioiodine (131I) therapy is indicated in patients with nearly all causes of hyperthyroidism. It may safely be given to patients of all age groups but is less often given to children under 10 years old. It is completely contraindicated in pregnancy and while breast feeding, but there is no increased risk of thyroid cancer, leukaemia or solid tumours. Administration of radioiodine must conform to regulations and definitions laid down by ARSAC And POPUMET. Medical staff authorising therapy must hold an ARSAC licence. The recommended strategy is to give an activity sufficient to render the patient rapidly euthyroid and maintain that state or achieve no more than a low rate of hypothyroidism in subsequent years. A range of activity (300-800 MBq) is suggested depending on the clinical state. Antithyroid drugs may be given before or after (or both) radioiodine if necessary. Full written information should be given to the patient and written consent obtained. A structured follow-up should be used ensuring regular measurement of TSH or FT4. Close cooperation with the patient's general practitioner is recommended throughout the assessment, treatment and follow-up. Shared care with a computer based follow-up system is recommended.

Cocrystals of 6-propyl-2-thiouracil: N-H···O versus N-H···S hydrogen bonds.

PubMed

Tutughamiarso, Maya; Egert, Ernst

2011-11-01

In order to investigate the relative stability of N-H···O and N-H···S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2-thiouracil (1/2), C(4)H(5)N(3)·2C(7)H(10)N(2)OS, (I), the `base pair' is connected by one N-H···S and one N-H···N hydrogen bond. Homodimers of 6-propyl-2-thiouracil linked by two N-H···S hydrogen bonds are observed in the cocrystal N-(6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2)·2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2-thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H···O and N-H···S hydrogen bonds. In all three structures, N-H···S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H···O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable.

Clinical update: treatment of hyperthyroidism in Graves' ophthalmopathy.

PubMed

Azzam, Ibrahim; Tordjman, Karen

2010-03-01

The presence of thyroid eye disease (TED) may influence the treatment of hyperthyroidism in patients with Graves' disease. Moreover, treatment of hyperthyroidism may affect the course of Graves' ophthalmopathy (GO). We review the literature and summarise recent knowledge about the impact of treatment modality for hyperthyroidism in GO. Anti-thyroid drugs (ATDs) remain the simplest and safest way to treat hyperthyroidism in patients with GO, but they are associated with a high relapse rate of hyperthyroidism and they have no effect on the course of GO. Radioactive iodine (RAI) treatment may be associated with exacerbation of GO especially in high risk patients, when glucocorticoid prophylaxis may be indicated. Large prospective trials are still lacking to define the exact effect of RAI on the course of GO, particularly in relation to other known risk factors. Likewise, clear guidelines for prophylactic glucocorticoid therapy are needed. RAI should be cautiously used in patients with more severe ophthalmopathy and concomitant I.V glucocorticoids should be considered. Thyroid surgery, whether total or subtotal thyroidectomy, has no effect on the course of ophthalmopathy. However, total thyroid ablation that combines surgery with radioactive iodine, as a means of achieving thyroid antigen disappearance, is increasingly gaining attention for the treatment of patients with GO, especially those undergoing thyroid surgery, but also for those with severe unresponsive ophthalmopathy. Studies supporting this approach are awaited.

Association Between Serum Levels of Adipocyte Fatty Acid-binding Protein and Free Thyroxine

PubMed Central

Tseng, Fen-Yu; Chen, Pei-Lung; Chen, Yen-Ting; Chi, Yu-Chao; Shih, Shyang-Ron; Wang, Chih-Yuan; Chen, Chi-Ling; Yang, Wei-Shiung

2015-01-01

Abstract Adipocyte fatty acid-binding protein (AFABP) has been shown to be a biomarker of body weight change and atherosclerosis. Changes in thyroid function are associated with changes in body weight and risks of cardiovascular diseases. The association between AFABP and thyroid function status has been seldom evaluated. The aim of this study was to compare the serum AFABP concentrations in hyperthyroid patients and those in euthyroid individuals, and to evaluate the associations between serum AFABP and free thyroxine (fT4) levels. For this study, 30 hyperthyroid patients and 30 euthyroid individuals at a referral medical center were recruited. The patients with hyperthyroidism were treated with antithyroid regimens as clinically indicated. No medication was given to the euthyroid individuals. The body weight, body mass index, thyroid function, serum levels of AFABP, and biochemical data of both groups at baseline and at the 6th month were compared. Associations between AFABP and fT4 levels were also analyzed. At the baseline, the hyperthyroid patients had significantly higher serum AFABP levels than the euthyroid individuals (median [Q1, Q3]: 22.8 [19.4, 30.6] ng/mL vs 18.6 [15.3, 23.2] ng/mL; P = 0.038). With the antithyroid regimens, the AFABP serum levels of the hyperthyroid patients decreased to 16.6 (15.0, 23.9) ng/mL at the 6th month. No difference in the AFABP level was found between the hyperthyroid and the euthyroid groups at the 6th month. At baseline, sex (female vs male, ß = 7.65, P = 0.022) and fT4 level (ß = 2.51, P = 0.018) were significantly associated with AFABP levels in the univariate regression analysis. At the 6th month, sex and fT4 level (ß = 8.09, P < 0.001 and ß = 3.61, P = 0.005, respectively) were also significantly associated with AFABP levels. The associations between sex and fT4 level with AFABP levels remained significant in the stepwise multivariate regression analysis, both at baseline and at the 6th month. The patients with hyperthyroidism had higher serum AFABP levels than the individuals with euthyroidism. In the patients with hyperthyroidism, the serum AFABP concentrations decreased after the antithyroid treatment. In this study, the serum AFABP concentrations were positively associated with female sex and the serum fT4 level. PMID:26469926

Urinary iodine in early pregnancy is associated with subclinical hypothyroidism in Tianjin, China: an observational study.

PubMed

Wang, Kunling; Zhang, Jie; Li, Fengao; Zhang, Wanqi; Wang, Hao; Ding, Li; Liu, Yaxin; Lin, Laixiang; Zhang, Shuang; Zhu, Mei

2017-02-17

Subclinical hypothyroidism (SH) is associated with adverse obstetric outcomes and neurodevelopment disorders. Both iodine deficiency and excess are associated with SH; however, few data regarding iodine nutrition status of pregnant women with SH are available. This study aimed to clarify whether iodine deficiency or excess is associated with SH, especially, when test results for anti-thyroid autoantibodies are negative. A total of 115 women with SH and 104 women with euthyroidism (EH) in early pregnancy in Tianjin, China were investigated, and their serum thyroid-stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), anti-thyroid globulin antibody (TGAb), urinary iodine (UIC), and urinary creatinine (UCr) concentrations were measured. Thyroid ultrasonography was performed to determine thyroid echogenicity and volume. The UIC, UIC/UCr ratio, prevalence of TPOAb and TGAb positivity, and thyroid gland volume were compared between the EH and SH groups. UIC and ultrasonographic features were analysed in subjects in the SH group who were negative for TPOAb and TGAb. Median UIC of SH (154.0 μg/L) and EH (150.1 μg/L) met the World Health Organization criterion for iodine sufficiency in pregnant women. Neither UIC nor the UIC/UCr ratio differed significantly between groups. The prevalence of TPOAb and TGAb positivity in the SH group was significantly higher than that in the EH group (P < 0.01). The percentage of subjects with UIC ≥ 250 μg/L in the SH group was significantly higher than that in the EH group (p = 0.004). The percentage of subjects negative for autoantibodies and UIC ≥ 250 μg/L in the SH group tended to be higher than that in subjects in the EH group negative for autoantibodies, but the difference was not statistically significant (p = 0.025, adjusted test level α = 0.0167). Eight of 18 subjects in the SH group with negative results for TPOAb and TGAb were diagnosed with Hashimoto thyroiditis by means of thyroid ultrasonography. Women in early pregnancy with SH in Tianjin were iodine sufficient, but still at risk of iodine deficiency as pregnancy progressed. UIC ≥ 250 μg/L was associated with increased risk of SH. Serological negative autoimmune thyroiditis and UIC ≥ 250 μg/L may play a role in pathogenesis of SH cases with negative results for autoantibodies.

[Severe hyperlipidemia, secondary to hypothyroidism due to atrophic thyroiditis in a girl].

PubMed

Pacín, Mirta

2009-02-01

We present a 5 years 8 months old girl with severe hyperlipidemia (high total cholesterol, and low density lipoprotein values, and also, ectopic fat pericardial deposit). She was treated with diet and cholestyramine, without diagnosis of her disease etiology. Growth detention, weight loss, retarded bone age and clinical signs of hypometabolism were recorded. Thyroid profile confirms hypothyroidism diagnosis. Based on positive anti-thyroid antibodies and clearly reduced thyroid volume, a diagnosis of autoimmune atrophic thyroiditis was made, a very unusual pathology in early infancy. Linear growth was affected by late diagnosis.

Age impact on autoimmune thyroid disease in females

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women.

PubMed

Seungdamrong, Aimee; Steiner, Anne Z; Gracia, Clarisa R; Legro, Richard S; Diamond, Michael P; Coutifaris, Christos; Schlaff, William D; Casson, Peter; Christman, Gregory M; Robinson, Randal D; Huang, Hao; Alvero, Ruben; Hansen, Karl R; Jin, Susan; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

2017-10-25

To study whether preconceptual thyroid-stimulating hormone (TSH) and antithyroid peroxidase (TPO) antibodies are associated with poor reproductive outcomes in infertile women. Secondary analysis of data from two multicenter, randomized, controlled trials conducted by the Reproductive Medicine Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Multivariable logistic regression analyses were performed to assess the association between preconceptual TSH levels and anti-TPO antibodies. Not applicable. Serum samples from 1,468 infertile women were utilized. None. Cumulative conception, clinical pregnancy, miscarriage, and live birth rates were calculated. Conception, clinical pregnancy, miscarriage, and live birth rates did not differ between patients with TSH ≥2.5 mIU/L vs. TSH < 2.5 mIU/L. Women with anti-TPO antibodies had similar conception rates (33.3% vs. 36.3%) but higher miscarriage rates (43.9% vs. 25.3%) and lower live birth rates (17.1% vs. 25.4%) than those without anti-TPO antibodies. Adjusted, multivariable logistic regression models confirmed elevated odds of miscarriage (odds ratio 2.17, 95% confidence interval 1.12-4.22) and lower odds of live birth (oddr ratio 0.58, 95% confidence interval 0.35-0.96) in patients with anti-TPO antibodies. In infertile women, preconceptional TSH ≥2.5 mIU/L is not associated with adverse reproductive outcomes; however, anti-TPO antibodies are associated with increased risk of miscarriage and decreased probability of live birth. PPCOS II NCT00719186; AMIGOS NCT01044862. Copyright © 2017. Published by Elsevier Inc.

GLP-1 and GIP Levels in Patients With Hyperthyroidism: The Effect of Antithyroid Treatment.

PubMed

Cira, Duygu Kalkan; Sari, Ramazan; Ozdem, Sebahat; Yilmaz, Nusret; Bozkurt, Selen

2017-08-01

Incretin hormones (glucagon-like peptide-1 [GLP-1] and gastric inhibitory polypeptide [GIP]) may play a role in the development of glucose intolerance and hyperglycemia in patients with hyperthyroidism. We aimed to assess both incretin levels and treatment-induced changes in incretin levels in those with hyperthyroidism. A total of 24 subjects (12 with hyperthyroidism and 12 healthy) were enrolled in the study. Oral glucose tolerance test was performed and serum glucose, insulin GLP1, and GIP levels were evaluated at 0 (baseline), 30, 60, 90, and 120 minutes using ELISA. Measurements were repeated after euthyroidism was reached in subjects with hyperthyroidism. The baseline glucose level was higher in those with hyperthyroidism compared with controls ( P = 0.03). GLP-1 and GIP responses to oral glucose load did not differ significantly between those with hyperthyroidism and controls. Peak GLP-1 and GIP levels were reached in both groups at 60 and 90 minutes, respectively. Areas under the curve (AUCs) for GLP1 and GIP were similar in those with hyperthyroidism and controls. Although GLP-1 and GIP levels did not change before and after antithyroid treatment in subjects with hyperthyroidism, time to peak GLP-1 and GIP levels were reached at 30 minutes after euthyroid state was achieved. Reversal of hyperthyroid to euthyroid status did not induce significant changes in AUCs for incretins. The findings of the present study suggest that the total incretin response to oral glucose load is preserved in patients with hypertyhroidism, but peak incretin responses may change after achieving euthyroid state.

Association of antithyroid peroxidase antibody with fibromyalgia in rheumatoid arthritis.

PubMed

Ahmad, Jowairiyya; Blumen, Helena; Tagoe, Clement E

2015-08-01

To investigate how autoimmune thyroiditis (ATD) affects the clinical presentation of established rheumatoid arthritis (RA) with particular reference to fibromyalgia and chronic widespread pain (CWP). A cohort of 204 patients with RA for whom the presence or absence of autoimmune thyroid antibodies was documented was examined for the relationships between thyroid autoantibodies and fibromyalgia or CWP. We identified 29 % who tested positive for antithyroid peroxidase antibodies (TPOAb). The anti-thyroglobulin antibody (TgAb) was found in 24 %. Among the thyroid autoantibody-positive patients, 40 % had a diagnosis of fibromyalgia or CWP versus 17 % for antibody negative patients. Logistic regression analyses (adjusted by age, sex, diabetes and BMI) indicated that TPOAb-positive patients were more likely to have fibromyalgia or CWP, with an odds ratio (OR) of 4.641, 95 % confidence interval (CI) (2.110-10.207) P < .001. Adjusting for spinal degenerative disc disease did not change the association with fibromyalgia, OR 4.458, 95 % CI (1.950-10.191), P < .001. The OR between TgAb and fibromyalgia was not significant (P > .05). Additional logistic regression analyses (adjusted by age, sex and BMI) indicated a significant relationship between TPOAb and fibromyalgia or CWP in patients without diabetes and those without hypothyroidism (OR of 4.873, 95 % CI (1.877-12.653), P = .001 and OR of 4.615 95 % CI (1.810-11.770), P = .001, respectively). There may be a positive association between the ATD antibody TPOAb, and fibromyalgia syndrome and CWP in patients with established RA.

Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune thyroiditis based on histopathologic results.

PubMed

Rho, Myung Ho; Kim, Dong Wook; Hong, Hyun Pyo; Park, Young Mi; Kwon, Min Jeong; Jung, Soo Jin; Kim, Young Wook; Kang, Taewoo

2012-12-01

Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the diagnostic accuracy of TPOAb detection using histopathologic reference standards. To fill this research gap, this study assessed the diagnostic accuracy of detection of TPOAb and that of other serological markers in asymptomatic patients who had been diagnosed with AIT by histopathologic analysis after thyroid surgery. After review of patient records, 598 patients who had undergone thyroid nodule surgery were enrolled for examination for thyroid parenchyma by a pathologist and classification into no co-existing lymphocytic thyroiditis, Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT). The correlation between patient serological data and thyroid parenchyma pathology was analyzed. Statistically significant differences (P < 0.05) were found between co-existing lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb titer was significantly associated with the degree of inflammation. An abnormal TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb titer is associated with the degree of thyroid inflammation and that detection of TPOAb is a very specific means of diagnosing AIT. The results also indicate that the incidence of AIT and PTC coexistence is relatively high.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

PubMed

Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2017-07-01

The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study. Copyright © 2017 Endocrine Society

Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1.

PubMed

Velkoska Nakova, V; Krstevska, B; Dimitrovski, Ch; Simeonova, S; Hadzi-Lega, M; Serafimoski, V

2010-01-01

The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during pregnancy in women with diabetes type 1 and gestational diabetes mellitus (GDM). The study group included 83 pregnant women who attended the Outpatient Department of the Endocrinology, Diabetes and Metabolic Disorders Clinic in the period from 05.2009 to 11.2009. The one hundred-g. oral glucose tolerance test (OGTT) was conducted on the pregnant women except for women with diabetes type 1. Thyroid functions were evaluated in all the pregnant women. After routine screening for GDM, thirty of the pregnant women were healthy and GDM was diagnosed in forty of them. The rest, thirteen women, had diabetes type 1. The women who developed GDM showed a mean free thyroxin concentration (fT4) significantly lower than that observed in the healthy pregnant women and women with diabetes type 1. Among the pregnant women with GDM, 10 women or 25% had fT4 concentrations below the lower cut-off with normal thyroid-stimulating hormone concentrations (TSH). A statistically significant difference was found in the prevalence of antithyroid antibodies (anti-TPO) between the (30%) women with diabetes type 1 and (10%) healthy pregnant women (p<0.05). In the women positive for anti-TPO, TSH was significantly higher (p<0.05). The significantly higher prevalence of hypothyroxinemia in GDM pregnancies and anti-TPO titres in pregnancies with diabetes type 1, than in healthy pregnant women warrants routine screening for thyroid abnormalities in these groups of pregnant women.

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.

Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

PubMed Central

Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

2014-01-01

Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions. PMID:24550448

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects

PubMed Central

Singhal, Neha; Praveen, V. P.; Bhavani, Nisha; Menon, Arun S.; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R. V.; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Context: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. Aim: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Subjects and Methods: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Statistical Analysis Used: Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Results: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). Conclusion: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease. PMID:27042408

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

PubMed

Singhal, Neha; Praveen, V P; Bhavani, Nisha; Menon, Arun S; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R V; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

The experience of gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease.

PubMed

Hong, Yun; Yu, Shi-Tong; Cai, Qian; Liang, Fa-Ya; Han, Ping; Huang, Xiao-Ming

2016-10-01

The aim of this study was to evaluate the safety, feasibility, effectiveness, and cosmesis of a gasless endoscopic-assisted thyroidectomy via the anterior chest in patients with Graves' disease. We retrospectively reviewed 38 patients with Graves' disease treated with thyroidectomy from November 2007 to June 2015. We analyzed clinical characteristics of patients, type of operation, operative indications, operative duration, length of postoperative hospital stay, and postoperative complications. The thyroidectomies were classified as total thyroidectomy (n = 12) or near-total thyroidectomy with a remnant of <1 g (n = 26). Surgical indications were recurrence after antithyroid drugs (ATDs) and unwillingness to undergo radioiodine therapy (n = 27), local compressive symptoms (n = 2), adverse drug reactions to ATDs (n = 5), and patient's preference (n = 4). Mean resection weight was 71.7 ± 16.2 g (range 44-109 g), mean operative duration 87.7 ± 17.3 min (range 66-136 min), intraoperative blood loss 70.6 ± 11.3 mL (range 43-92 mL), and drainage was 42.0 ± 8.5 mL (range 20-62 mL). Temporary postoperative recurrent laryngeal nerve palsy and temporary hypoparathyroidism occurred in 3 cases (7.89 %) each. Mean hospital stay was 2.5 ± 0.3 days (range 2-4 days). There was no recurrence of hyperthyroidism over the follow-up period of for 68.1 ± 5.6 months (range 6-89 months). All patients were satisfied with their cosmetic results. Gasless endoscopic-assisted thyroidectomy via the anterior chest approach for Graves' disease is a safe, feasible, and effective and provides an excellent cosmetic outcome procedure. It is a valid option in appropriately selected patients.

Study of the Factors Leading to Fetal and Neonatal Dysthyroidism in Children of Patients With Graves Disease.

PubMed

Banigé, Maïa; Estellat, Candice; Biran, Valerie; Desfrere, Luc; Champion, Valerie; Benachi, Alexandra; Ville, Yves; Dommergues, Marc; Jarreau, Pierre-Henri; Mokhtari, Mostafa; Boithias, Claire; Brioude, Frederic; Mandelbrot, Laurent; Ceccaldi, Pierre-François; Mitanchez, Delphine; Polak, Michel; Luton, Dominique

2017-06-01

Neonatal hyperthyroidism was first described in 1912 and in 1964 was shown to be linked to transplacental passage of maternal antibodies. Few multicenter studies have described the perinatal factors leading to fetal and neonatal dysthyroidism. To show how fetal dysthyroidism (FD) and neonatal dysthyroidism (ND) can be predicted from perinatal variables, in particular, the levels of anti-thyrotropin receptor antibodies (TRAbs) circulating in the mother and child. This was a retrospective multicenter study of data from the medical records of all patients monitored for pregnancy from 2007 to 2014. Among 280,000 births, the medical records of 2288 women with thyroid dysfunction were selected and screened, and 417 women with Graves disease and positive for TRAbs during pregnancy were included. Using the maternal TRAb levels, the cutoff value of 2.5 IU/L best predicted for FD, with a sensitivity of 100% and specificity of 64%. Using the newborn TRAb levels, the cutoff value of 6.8 IU/L best predicted for ND, with a sensitivity of 100% and a specificity of 94%. In our study, 65% of women with a history of Graves disease did not receive antithyroid drugs during pregnancy but still had infants at risk of ND. In pregnant women with TRAb levels ≥2.5 IU/L, fetal ultrasound monitoring is essential until delivery. All newborns with TRAb levels ≥6.8 IU/L should be examined by a pediatrician with special attention for thyroid dysfunction and treated, if necessary.

Predictive factors of outcomes in personalized radioactive iodine ((131)I) treatment for Graves' disease.

PubMed

Liu, Min; Jing, Danqing; Hu, Jingsheng; Yin, Shinan

2014-10-01

Graves' disease (GD) is the most common cause of hyperthyroidism in iodine-sufficient areas. Radioactive iodine I treatment (RIT), as the 1st therapeutic option, is widely accepted by doctors and patients. The aim of this study was to investigate factors influencing the success rate of calculated RIT in GD. Thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was verified retrospectively at least 1 year after RIT and was compared with presenting clinical characteristics and pre-RIT parameters in 167 patients with GD treated with I-iodide in the authors' institute. After RIT, 83 patients (49.7%) became euthyroid, 64 patients (38.3%) became hypothyroid and 20 (12.0%) remained hyperthyroid. Multiple logistic regression analyses demonstrated that there was no statistically significant association between RIT outcomes and sex, age, history of GD, previous antithyroid drug treatment, thyroid hormone levels, thyroid gland mass or radioactive iodine I dosage. The only variables associated with the success rate were the course of disease over 6 months (odds ratio, 3.70; confidence interval, 1.75-7.17; P = 0.014) and 2-hour radioactive iodine uptake (RAIU) >58.5% (odds ratio, 4.08; confidence interval, 2.03-7.83; P = 0.005). Our study has shown that a calculated approach for the treatment of GD was effective, but high failure rates were observed in patients presenting higher 2-hour RAIU, particularly those with 2-hour RAIU of more than 58.5%.

Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review.

PubMed

Bettencourt-Silva, Rita; Pereira, Josué; Belo, Sandra; Magalhães, Daniela; Queirós, Joana; Carvalho, Davide

2018-01-01

The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

Treatment choice, satisfaction and quality of life in patients with Graves' disease.

PubMed

Conaglen, Helen M; Tamatea, Jade A U; Conaglen, John V; Elston, Marianne S

2018-04-06

Thyrotoxicosis, most often caused by Graves' disease (GD), when treated inadequately may result in premature mortality. There is little consensus as to which of the 3 treatment options available - antithyroid drugs (ATD), radioactive iodine (RAI) and surgery, is better. (i) To assess factors involved in treatment choice and treatment satisfaction in patients treated for Graves' disease; (ii) To assess quality of life (QoL) following treatment of Graves' disease. Participants were selected from a prospective study cohort assessing thyrotoxicosis incidence and severity. Of the 172 eligible patients with Graves' disease, 123 treated patients participated (64% had received ATD only, 11% RAI and 25% total thyroidectomy, the latter 2 usually after a period of ATD), along with 18 untreated patients with newly diagnosed Graves' disease (overall participation rate, 73%). Consented patients completed a questionnaire detailing factors involved in treatment choice, QoL and satisfaction with treatment. Participants reported that the most important factors in choosing a treatment were the following: the effects on activities of daily living, concern about use of radioiodine, possibility of depression or anxiety, and doctor's recommendations. Satisfaction levels were high across all 3 treatment types. QoL 1-year following treatment was higher than in untreated patients, and comparable with other international studies. Patient satisfaction with therapy and QoL does not differ by treatment type. Therefore, clinical and social factors, in combination with patient choice and resource availability, should determine which treatment modality patients with Graves' disease should receive. © 2018 John Wiley & Sons Ltd.

Clinical challenges of thyroid eye disease in HIV-positive patients on highly active antiretroviral therapy.

PubMed

Edmunds, Matthew R; Mellington, Faye; Ford, Rebecca L; Torlinska, Barbara; Manavi, Kaveh; Boelaert, Kristien

2015-03-01

Graves' disease (GD) as an immune reconstitution inflammatory syndrome during highly active antiretroviral therapy (HAART) for HIV has previously been reported. However, clinical challenges associated with HIV in the context of thyroid eye disease (TED) are not as well-characterized. To determine the frequency of coexisting HIV and TED, describe TED presentation and course in the context of HIV, and evaluate management difficulties as well as potential solutions. Cross-sectional study of all patients with coexisting GD and HIV at University Hospitals Birmingham (2003-2014). Retrospective case note review to identify TED with particular reference to HAART regimen, CD4+ T-cell count, HIV viral load, and TED activity and severity. Of 783 subjects with GD and 1186 with HIV, 11 were identified with both GD and HIV. Of these, three had clinical features of TED; each was of Afro-Caribbean origin, was in their fourth decade, and initially presented with undetectable CD4 T cells and high HIV viral loads. All went on to develop GD >3 years after commencing HAART, with normal CD4 count and undetectable viral load at the time of GD diagnosis. The full spectrum of TED was represented, with two subjects requiring orbital decompression surgery. TED in the context of HIV is uncommon. Many challenges exist in such patients, particularly HAART drug interactions with antithyroid and immunosuppressant medications. To better understand TED in HIV and to counsel patients with this copathology most effectively, future multicenter surveillance is required.

Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis.

PubMed

Rosario, P W; Santos, J B N; Nunes, N S; da Silva, A L; Calsolari, M R

2014-06-01

The objective of this prospective study was to compare the results of color flow Doppler sonography (CFDS) and radioiodine scintigraphy in patients with thyrotoxicosis. A total of 176 patients, 102 with clinical thyrotoxicosis and 74 with subclinical dysfunction, were included. Pregnant and breast-feeding women, patients using amiodarone or recently exposed to iodinated contrast, and patients treated with antithyroid drugs were excluded. Total T3, free T4, TSH, and anti-TSH receptor antibodies were measured before scintigraphy and CFDS. Excluding one patient whose etiology of thyrotoxicosis remained undefined, CFDS showed 100% specificity. In fact, in all 10 cases in which scintigraphy and CFDS provided discordant results, the diagnosis suggested by the latter was correct. In patients with clinical thyrotoxicosis, the sensitivity of CFDS was 96% for diffuse toxic goiter, 95% for the absence of hyperfunction, and 100% for toxic nodular disease. In patients with subclinical dysfunction, the sensitivity of CFDS was 72.7% for diffuse toxic goiter, 90% for toxic adenoma, and 86.6% for toxic multinodular disease. CFDS was inconclusive in patients with parenchymal blood flow with patchy uneven distribution or with macronodules in which nodule vascularity compared to the remaining parenchyma did not permit to establish the diagnosis with certainty. CFDS can be used instead of scintigraphy not only in situations in which the latter is contraindicated or of limited value to define the etiology of thyrotoxicosis. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of high dose methylprednisolone pulse therapy followed by oral prednisolone administration on the production of anti-TSH receptor antibodies and clinical outcome in Graves' disease.

PubMed

Kubota, Sumihisa; Ohye, Hidemi; Nishihara, Eijun; Kudo, Takumi; Ito, Mitsuru; Fukata, Shuji; Amino, Nobuyuki; Kuma, Kanji; Miyauchi, Akira

2005-12-01

Little is known about the immunosuppressive effect of glucocorticoids on TSH receptor antibodies. We observed the long-term prognosis and serum TSH binding inhibitor immunoglobulin (TBII) levels in patients with Graves' ophthalmopathy who had received intravenous methylprednisolone pulse therapy (pulse therapy) followed by oral prednisolone administration in order to ascertain how long the immunosuppressive effect of glucocorticoids continued. This is the first report on the effect of pulse therapy on Graves' disease outcome. We observed 67 patients who were treated by antithyroid drugs (ATD) alone for 2 years after pulse therapy. TBII was evaluated before and 3, 6, 12, 18, and 24 months after pulse therapy. The mean TBII decreased significantly 3 months after pulse therapy (p<0.001), and was maintained until 24 months. There were 24 patients whose TBII was positive (>15%) at 24 months, in whom the mean TBII decreased significantly 3 to 6 months after pulse therapy (p<0.001), but increased again at 12 to 24 months (p<0.05). Thus, the immunosuppressive effect of glucocorticoids may be lost at 12 months after pulse therapy in these patients. The remission rate in the pulse therapy group was 40.98%, and that of the control patient group was 48.57%. There was no significant difference between the two. These results suggest that the immunosuppressive effect of pulse therapy was temporary, and that pulse therapy did not increase remission rate of Graves' disease.

Hyperthyroidism in Childhood: Causes, When and How to Treat

PubMed Central

Léger, Juliane; Carel, Jean Claude

2013-01-01

Graves’ disease (GD) is the most common cause of hyperthyroidism in children. This review gives an overview and update of management of GD. Antithyroid drugs (ATD) are recommended as the initial treatment, but the major problem is the high relapse rate (30%) as remission is achieved after a first course of ATD. More prolonged medical treatment may increase the remission rate up to 50%. Alternative treatments, such as radioactive iodine or thyroidectomy, are considered in cases of relapse, lack of compliance, or ATD toxicity. Therefore, clinicians have sought prognostic indicators of remission. Relapse risk decreases with longer duration of the first course of ATD treatment, highlighting the positive impact of a long period of primary ATD treatment on outcome. The identification of other predictive factors such as severe biochemical hyperthyroidism at diagnosis, young age, and absence of other autoimmune conditions has made it possible to stratify patients according to the risk of relapse after ATD treatment, leading to improvement in patient management by facilitating the identification of patients requiring long-term ATD or early alternative therapy. Neonatal autoimmune hyperthyroidism is generally transient, occurring in only about 2% of the offspring of mothers with GD. Cardiac insufficiency, intrauterine growth retardation, craniostenosis, microcephaly and psychomotor disabilities are the major risks in these infants and highlight the importance of thyroid hormone receptor antibody determination throughout pregnancy in women with GD, as well as highlighting the need for early diagnosis and treatment of hyperthyroidism. Conflict of interest:None declared. PMID:23154161

Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review.

PubMed

Kyriacou, Angelos; McLaughlin, John; Syed, Akheel A

2015-10-01

Thyroid disorders commonly impact on the gastrointestinal system and may even present with gastrointestinal symptoms in isolation; for example, metastatic medullary thyroid carcinoma typically presents with diarrhoea. Delays in identifying and treating the underlying thyroid dysfunction may lead to unnecessary investigations and treatment, with ongoing morbidity, and can potentially be life-threatening. Similarly, gastrointestinal diseases can impact on thyroid function tests, and an awareness of the concept and management of non-thyroidal illness is necessary to avoid giving unnecessary thyroid therapies that could potentially exacerbate the underlying gastrointestinal disease. Dual thyroid and gastrointestinal pathologies are also common, with presentations occurring concurrently or sequentially, the latter after a variable time lag that can even extend over decades. Such an association aetiologically relates to the autoimmune background of many thyroid disorders (e.g. Graves' disease and Hashimoto's thyroiditis) and gastrointestinal disorders (e.g. coeliac disease and inflammatory bowel disease); such autoimmune conditions can sometimes occur in the context of autoimmune polyglandular syndrome. Emphasis should also be given to the gastrointestinal side effects of some of the medications used for thyroid disease (e.g. anti-thyroid drugs causing hepatotoxicity) and vice versa (e.g. interferon therapy causing autoimmune thyroid dysfunction). In this review, we discuss disorders of the thyroid-gut axis and identify the evidence base behind the management of such disorders. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

[Treatment of Graves Hyperthyroidism by Jiakangling Capsule Combined with Reduction of 131I: an Efficacy Observation].

PubMed

Liu, Guan-xin; Liao, Ning

2016-01-01

To observe the clinical efficacy of Jiakangling Capsule (JC) combined with reduction of 1311 in treatment of Graves hyperthyroidism. Totally 387 Graves hyperthyroidism patients were randomly assigned to the treatment group (200 cases) and the control group (187 cases). Patients in the treatment group took JC combined with reduction of 131I. The 131I dosage per gram of thyroid tissue was 50-80 microCi. They additionally took JC one week after taking 1311 for one consecutive month. Patients in the control group took 131 routinely as one disposable treatment. The 131I dosage per gram of thyroid tissue was 70-120 microCi, without using JC or other anti-thyroid drugs. All patients were reexamined after 24-month treatment. Whether hyperthyroidism was cured, incurred, or permanent was observed. Efficacies of thyroglobulin antibody (TGAb) and thyroid microsome antibody (TMAb) were compared between the two groups. Compared with the control group, the incurred ratio increased in the treatment group [3.2% (6/187) vs. 16.0% (32/200), P < 0.01], the incurred ratio of strong positive TGAb and TMAb patients increased [3.5% (2/57) vs. 27.1% (16/59), P < 0.01], the permanent hypothyroidism ratio decreased [21.1% (12/57) vs. 3.4% (2/59), P < 0.05 ]. JC combined with reduction of 1311 was superior in treating Graves hyperthyroidism induced permanent hypothyroidism than routine 1311 treatment, especially for strong positive TGAb and TMAb patients.

Hyperthyroidism in childhood: causes, when and how to treat.

PubMed

Léger, Juliane; Carel, Jean Claude

2013-01-01

Graves' disease (GD) is the most common cause of hyperthyroidism in children. This review gives an overview and update of management of GD. Antithyroid drugs (ATD) are recommended as the initial treatment, but the major problem is the high relapse rate (30%) as remission is achieved after a first course of ATD. More prolonged medical treatment may increase the remission rate up to 50%. Alternative treatments, such as radioactive iodine or thyroidectomy, are considered in cases of relapse, lack of compliance, or ATD toxicity. Therefore, clinicians have sought prognostic indicators of remission. Relapse risk decreases with longer duration of the first course of ATD treatment, highlighting the positive impact of a long period of primary ATD treatment on outcome. The identification of other predictive factors such as severe biochemical hyperthyroidism at diagnosis, young age, and absence of other autoimmune conditions has made it possible to stratify patients according to the risk of relapse after ATD treatment, leading to improvement in patient management by facilitating the identification of patients requiring long-term ATD or early alternative therapy. Neonatal autoimmune hyperthyroidism is generally transient, occurring in only about 2% of the offspring of mothers with GD. Cardiac insufficiency, intrauterine growth retardation, craniostenosis, microcephaly and psychomotor disabilities are the major risks in these infants and highlight the importance of thyroid hormone receptor antibody determination throughout pregnancy in women with GD, as well as highlighting the need for early diagnosis and treatment of hyperthyroidism.

Characterization of thyroid function and antithyroid antibody tests among Saudis

PubMed Central

Jammah, Anwar A.; Alshehri, Anwar S.; Alrakhis, Afaf A.; Alhedaithy, Asma S.; Almadhi, Asma M.; Alkwai, Hala M.; Alhamad, Maram M.; Alzahrani, Saad H.

2015-01-01

Objective: To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population. Methods: A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity. Results: Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p<0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies. Conclusion: The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies. PMID:25987111

Antigastric parietal cell and antithyroid autoantibodies in patients with recurrent aphthous stomatitis.

PubMed

Wu, Yang-Che; Wu, Yu-Hsueh; Wang, Yi-Ping; Chang, Julia Yu-Fong; Chen, Hsin-Ming; Sun, Andy

2017-01-01

Anti-gastric parietal cell antibody (GPCA), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA) have not yet been reported in patients with recurrent aphthous stomatitis (RAS). This study mainly assessed the frequencies of the presence of serum GPCA, TGA, and TMA in different types of RAS patients. Serum GPCA, TGA, and TMA levels were measured in 355 RAS patients of different subtypes and in 355 age- and sex-matched healthy control individuals. We found that 13.0%, 19.4%, and 19.7% of 355 RAS patients, 16.7%, 23.3%, and 21.7% of 60 major-typed RAS patients, 12.2%, 18.6%, and 19.3% of 295 minor-typed RAS patients, 18.1%, 20.0%, and 21.9% of 160 atrophic glossitis-positive RAS (AG+/RAS) patients, and 8.7%, 19.0%, and 17.9% of 195 AG-negative RAS (AG-/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. RAS, major-typed RAS, minor-typed RAS, AG+/RAS, and AG-/RAS patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control individuals (all p < 0.001). Of 65 TGA/TMA-positive RAS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 76.9%, 12.3%, and 10.8% of these TGA/TMA-positive RAS patients had normal, lower, and higher serum TSH levels, respectively. We conclude that approximately one-third RAS patients may have GPCA/TGA/TMA positivity in their sera. Because some GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and some TGA/TMA-positive patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these patients should be referred to doctors for further management. Copyright © 2016. Published by Elsevier B.V.

Antigastric parietal cell and antithyroid autoantibodies in patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Chiang, Chun-Pin; Wang, Yi-Ping; Wu, Yang-Che; Chen, Hsin-Ming; Sun, Andy

2017-04-01

Desquamative gingivitis (DG) is principally associated with erosive oral lichen planus (EOLP), mucous membrane pemphigoid (MMP), and pemphigus vulgaris (PV). Serum autoantibodies including antigastric parietal cell antibody (GPCA), antithyroglobulin antibody (TGA), and antithyroid microsomal antibody (TMA) were measured in 500 patients with DG, 287 EOLP without DG (EOLP/DG - ) patients, and 100 healthy control subjects. The 500 patients with DG were diagnosed as having EOLP in 455 (91%), PV in 40 (8%), and MMP in five (1%) patients. We found that 37.0%, 43.6%, and 42.6% of 500 patients with DG, 39.6%, 46.4%, and 45.1% of 455 EOLP with DG (EOLP/DG) patients, and 18.5%, 27.5%, and 30.3% of 287 EOLP/DG - patients had the presence of GPCA, TGA, and TMA in their sera, respectively. DG, EOLP/DG, and EOLP/DG - patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). Moreover, 455 EOLP/DG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than 287 EOLP/DG - patients (all P-values < 0.001). Of 210 TGA/TMA-positive patients with DG whose serum thyroid-stimulating hormone (TSH) levels were measured, 84.3%, 6.7%, and 9.0% patients had normal, lower, and higher serum TSH levels, respectively. We conclude that 73.4% DG, 77.1% EOLP/DG, and 47.4% EOLP/DG - patients may have GPCA/TGA/TMA positivity in their sera. Because part of GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive patients may have thyroid dysfunction, these patients should be referred to medical department for further management. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

PubMed Central

Kobayashi, Tomoko; Iwama, Shintaro; Yasuda, Yoshinori; Okada, Norio; Tsunekawa, Taku; Onoue, Takeshi; Takagi, Hiroshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Goto, Motomitsu; Suga, Hidetaka; Banno, Ryoichi; Yokota, Kenji; Hase, Tetsunari; Morise, Masahiro; Hashimoto, Naozumi; Ando, Masahiko; Kiyoi, Hitoshi; Gotoh, Momokazu; Ando, Yuichi; Akiyama, Masashi; Hasegawa, Yoshinori; Arima, Hiroshi

2018-01-01

Abstract Context Immune checkpoint inhibitors, including anti–programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. Objective This study examined the incidence of endocrine irAEs induced by nivolumab. Patients and Main Outcome Measured Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Results Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti–thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Conclusions Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit. PMID:29600292

Characterization of thyroid function and antithyroid antibody tests among Saudis.

PubMed

Jammah, Anwar A; Alshehri, Anwar S; Alrakhis, Afaf A; Alhedaithy, Asma S; Almadhi, Asma M; Alkwai, Hala M; Alhamad, Maram M; Alzahrani, Saad H

2015-06-01

To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population.   A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity.   Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p less than 0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies.   The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program.

PubMed

Mirhosseini, Naghmeh; Brunel, Ludovic; Muscogiuri, Giovanna; Kimball, Samantha

2017-12-01

Vitamin D deficiency has been associated with an increased risk of hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the influence of vitamin D supplementation on thyroid function and anti-thyroid antibody levels. We constructed a database that included 11,017 participants in a health and wellness program that provided vitamin D supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D] concentrations (>100 nmol/L). Participant measures were compared between entry to the program (baseline) and follow-up (12 ± 3 months later) using an intent-to-treat analysis. Further, a nested case-control design was utilized to examine differences in thyroid function over 1 year in hypothyroid individuals and euthyroid controls. More than 72% of participants achieved serum 25(OH)D concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L. Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum 25(OH)D concentrations ≥125 nmol/L were associated with a 30% reduced risk of hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies. Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at follow-up, which was a significant positive predictor of improved thyroid function. The results of the current study suggest that optimal thyroid function might require serum 25(OH)D concentrations above 125 nmol/L. Vitamin D supplementation may offer a safe and economical approach to improve thyroid function and may provide protection from developing thyroid disease.

Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.

PubMed

Møllehave, Line Tang; Linneberg, Allan; Skaaby, Tea; Knudsen, Nils; Ehlers, Lars; Jørgensen, Torben; Thuesen, Betina Heinsbæk

2018-03-01

Iodine fortification (IF) may contribute to changes in costs of thyroid disease treatment through changes in disease patterns. From a health economic perspective, assessment of the development in costs of thyroid disease treatment in the population is pertinent. To assess the trends in annual medicine and hospital costs of thyroid disease treatment during 1995-2015 in Denmark, i.e., before and after the introduction of mandatory IF in 2000. Information on treatments for thyroid disease (antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment) was obtained from nationwide registers. Costs were valued at 2015 prices using sales prices for medicines and the Danish Diagnosis-Related Group (DRG) and Danish Ambulatory Grouping System (DAGS) tariffs of surgeries/radioiodine treatments. Results were adjusted for changes in population size and age and sex distribution. The total direct medicine and hospital costs of thyroid disease treatment increased from EUR ∼190,000 per 100,000 persons in 1995 to EUR ∼270,000 per 100,000 persons in 2015. This was mainly due to linearly increased costs of thyroid hormone therapy and increased costs of thyroid surgery since 2008. Costs of antithyroid medication increased slightly and transiently after IF, while costs of radioiodine treatment remained constant. Costs of thyroid hormone therapy and thyroid surgery did not follow the development in the prevalence of hypothyroidism and structural thyroid diseases observed in concurrent studies. The costs of total direct medicine and hospital costs for thyroid disease treatment in Denmark increased from 1995 to 2015. This is possibly due to several factors, e.g., changes in treatment practices, and the direct effect of IF alone remains to be estimated.

[Hashimoto's encephalopathy and autoantibodies].

PubMed

Yoneda, Makoto

2013-04-01

Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of encephalopathy associated with thyroid disorders must be considered.

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases

PubMed Central

Nair, Rahul; Gambhir, Anushree; Kaur, Supreet; Pandey, Aditi; Shetty, Abhinav; Naragude, Piyusha

2018-01-01

Introduction Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. Aim Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). Materials and Methods The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. Results The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21–40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. Conclusion The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the “Gold Standard” for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical parameters are the key for diagnosis of other forms of thyroiditis. PMID:29686830

Clofibrate prevents and reverses the hemodynamic manifestations of hyperthyroidism in rats.

PubMed

Rodríguez-Gómez, Isabel; Cruz, Antonio; Moreno, Juan Manuel; Soler, Agatángelo; Osuna, Antonio; Vargas, Félix

2008-03-01

This study analyzed the effects of the chronic administration of clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist, on the development and established hemodynamic, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. The prevention study used four groups of male Wistar rats: control, clofibrate (240 mg/kg/day by gavage), T(4)(75 microg thyroxine/rat/day s.c.), and T(4)+clofibrate. All treatments were maintained for 3 weeks. Body weight (BW), tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, temperature, SBP, pulse pressure (PP) and HR were recorded in conscious rats, and morphologic, metabolic, plasma, and renal variables were measured. The reversion study used two groups of rats, T(4)(treated for 6 weeks) and T(4)+clofibrate, measuring their hemodynamic variables and temperature for 3 weeks. T(4) increased BP, HR, PP, and temperature when compared with control rats. Clofibrate prevented and reversed the increase in SBP, HR, PP, and temperature produced by T(4) administration, reduced plasma thyroid hormone levels, and increased plasma thyroid-stimulating hormone values and phenol-uridine diphosphate-glucuronosyl-transferase (UGT) activity. However, clofibrate did not modify the cardiac or renal hypertrophy, polyphagia, polydipsia, or proteinuria of hyperthyroid rats. In normal rats, clofibrate treatment did not significantly change thyroid hormone levels, phenol-UGT activity, or any hemodynamic, morphologic, or renal variables. Chronic clofibrate treatment suppressed the hemodynamic manifestations and increased temperature of hyperthyroidism, an effect that can be produced by direct antithyroid effects. However, clofibrate administration did not modify the morphologic, metabolic, or renal alterations of hyperthyroid rats, indicating specificity in the antithyroid actions of clofibrate.

The seroprevalence of antithyroid peroxidase antibodies in bipolar families and bipolar twins: results from two longitudinal studies.

PubMed

Snijders, G; de Witte, L; Mesman, E; Kemner, S; Vonk, R; Brouwer, R; Nolen, W A; Drexhage, H A; Hillegers, M H J

2017-12-01

Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s  = .72 p < .001 resp. r s  = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.

Unstable angina with normal coronary angiography in hyperthyroidism: a case report.

PubMed

Lin, Tsung-Hsien; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2005-01-01

Hyperthyroidism is associated with an increase in myocardial oxygen consumption that, due to an imbalance of oxygen demand and supply, can cause angina. However, subclinical hyperthyroidism rarely presents as chest pain in the resting state. Herein, we present a case of subclinical hyperthyroidism involving a 58-year-old male who complained of frequent chest tightness and typical electrocardiographic changes while in a resting state. Coronary angiography showed no significant lesion. Laboratory data showed that the patient suffered from hyperthyroidism, for which he was successfully treated with anti-thyroid agents. We are reminded that typical chest pain might be the first symptom of hyperthyroidism.

A case of thyroid storm with multiple organ failure effectively treated with plasma exchange.

PubMed

Sasaki, Kazuki; Yoshida, Akira; Nakata, Yukiko; Mizote, Isamu; Sakata, Yasushi; Komuro, Issei

2011-01-01

We describe a 48-year-old man with thyroid storm presenting with heart failure. He presented severely impaired left ventricular wall motion and a marked increase in the liver enzymes. He developed disseminated intravascular coagulation on day 2. Due to elevated serum thyroid hormone level, anti-thyroid hormone receptor antibody positivity, and his clinical symptoms, he was diagnosed as thyroid storm due to untreated Graves' disease. His condition did not improve even after 6 days of conventional therapy including steroids. After therapeutic plasma exchange was carried out, his thyroid hormone level decreased markedly. Consequently, his condition recovered gradually, and he was discharged at day 43.

Study of the Factors Leading to Fetal and Neonatal Dysthyroidism in Children of Patients With Graves Disease

PubMed Central

Estellat, Candice; Biran, Valerie; Desfrere, Luc; Champion, Valerie; Benachi, Alexandra; Ville, Yves; Dommergues, Marc; Jarreau, Pierre-Henri; Mokhtari, Mostafa; Boithias, Claire; Brioude, Frederic; Mandelbrot, Laurent; Ceccaldi, Pierre-François; Mitanchez, Delphine; Polak, Michel; Luton, Dominique

2017-01-01

Context: Neonatal hyperthyroidism was first described in 1912 and in 1964 was shown to be linked to transplacental passage of maternal antibodies. Few multicenter studies have described the perinatal factors leading to fetal and neonatal dysthyroidism. Objective: To show how fetal dysthyroidism (FD) and neonatal dysthyroidism (ND) can be predicted from perinatal variables, in particular, the levels of anti-thyrotropin receptor antibodies (TRAbs) circulating in the mother and child. Design and Patients: This was a retrospective multicenter study of data from the medical records of all patients monitored for pregnancy from 2007 to 2014. Setting: Among 280,000 births, the medical records of 2288 women with thyroid dysfunction were selected and screened, and 417 women with Graves disease and positive for TRAbs during pregnancy were included. Results: Using the maternal TRAb levels, the cutoff value of 2.5 IU/L best predicted for FD, with a sensitivity of 100% and specificity of 64%. Using the newborn TRAb levels, the cutoff value of 6.8 IU/L best predicted for ND, with a sensitivity of 100% and a specificity of 94%. In our study, 65% of women with a history of Graves disease did not receive antithyroid drugs during pregnancy but still had infants at risk of ND. Conclusions: In pregnant women with TRAb levels ≥2.5 IU/L, fetal ultrasound monitoring is essential until delivery. All newborns with TRAb levels ≥6.8 IU/L should be examined by a pediatrician with special attention for thyroid dysfunction and treated, if necessary. PMID:29130077

Hyperthyroidism in a population with Down syndrome (DS).

PubMed

Goday-Arno, Alberto; Cerda-Esteva, Mariaina; Flores-Le-Roux, Juana Antonia; Chillaron-Jordan, Juan José; Corretger, Josep Maria; Cano-Pérez, Juan Francisco

2009-07-01

Thyroid disorders are frequent in patients with Down syndrome (DS). It is well-known that the prevalence of hypothyroidism is high but data on hyperthyroidism are scarce. To assess the prevalence, aetiology, clinical characteristics, evolution and treatment of hyperthyroidism in a population with DS attending a specialized medical centre. Data were gathered by systematic review of 1832 medical records from the Catalan DS Foundation, in Spain, registered between January 1991 and February 2006. Patients with the diagnosis of hyperthyroidism were identified and data on clinical features, physical examination, laboratory and imaging tests, treatment and evolution were collected. Twelve patients with hyperthyroidism were recorded (6.5 cases/1000 patients with DS). There were 5 males and 7 females, with a mean age at diagnosis of 16.8 years. The most common presenting symptoms were decreased heat tolerance, sweating, increased irritability and weight loss. All patients had diffuse goitre at physical examination and two patients presented with exophthalmia. Clinical diagnosis was confirmed biochemically. Thyroid-stimulating immunoglobulin levels were raised (mean 128.1 U/l) and imaging tests confirmed the diagnosis of Graves' disease in all cases. Patients started treatment with carbimazole at diagnosis and after a mean period of 40 months without clinical remission, they required definitive therapy with radioactive iodine. Subjects developed hypothyroidism after radio-iodine therapy and replacement therapy with levothyroxine was necessary. Hyperthyroidism is more prevalent in patients with DS than in the general population and has no gender predominance. It is caused mainly by Graves' disease. Anti-thyroid drugs were not effective in achieving remission and radioactive iodine as a definitive treatment was required in all cases.

Polymyositis associated with hypothyroidism or hyperthyroidism: two cases and review of the literature.

PubMed

Wang, Han; Li, Hong; Kai, Cui; Deng, Juelin

2011-04-01

Studies confirming a possible relationship of polymyositis within thyroid dysfunction, either hypothyroidism or hyperthyroidism, are hardly available. To define the association, identify clinical, laboratory, electromyographic, and pathologic features in polymyositis (PM) patients with hypothyroidism or hyperthyroidism, we conducted a MEDLINE and Chinese biomedicine database search to identify relevant literature published in the past 25 years. Seventeen cases were included. All patients were female (10 hypothyroidism patients, seven hyperthyroidism patients). The mean (SD) age of PM, hypothyroidism, and hyperthyroidism at diagnosis was 54.8 (16.7), 55.5 (16.5), and 32.7 years (10.2), respectively. PM diagnosis can precede or parallel hypothyroidism while PM may occur following the diagnosis of hyperthyroidism. The most common comorbidities were malignant tumors in these disorders, including thymoma, colon cancer, and thyroid cancer. Muscle weakness was described in 100% of patients. Other common manifestations included muscles' atrophy and pain, deep tendon reflexes, polyarthralgia, and dysphagia. Most patients had markedly elevated creatine kinase and the presence of anti-Sjogren's syndrome A (SSA) antibodies was also found in two cases. Malignancy associated with PM may more frequently occur in hypothyroidism than in hyperthyroidism. The abnormalities on electromyography and biopsy did not differ from those findings of PM. Therapy consisting of corticosteroids, thyroid hormone, or anti-thyroid drugs was administrated; however, poor prognosis seemed to be associated with malignant tumors as well as older age and the presence of anti-SSA antibodies. It is reasonable to suggest that those patients should be routinely evaluated for thyroid function, especially in older female and patients suffering from cancers.

Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

PubMed

Bahn Chair, Rebecca S; Burch, Henry B; Cooper, David S; Garber, Jeffrey R; Greenlee, M Carol; Klein, Irwin; Laurberg, Peter; McDougall, I Ross; Montori, Victor M; Rivkees, Scott A; Ross, Douglas S; Sosa, Julie Ann; Stan, Marius N

2011-06-01

Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

MANAGEMENT OF ENDOCRINE DISEASE: Subclinical thyrotoxicosis: prevalence, causes and choice of therapy.

PubMed

Carlé, Allan; Andersen, Stine Linding; Boelaert, Kristien; Laurberg, Peter

2017-06-01

Subclinical thyrotoxicosis is a condition affecting up to 10% of the population in some studies. We have reviewed literature and identified studies describing prevalences, causes and outcomes of this condition. Treatment should be considered in all subjects if this biochemical abnormality is persistent, especially in case of symptoms of thyrotoxicosis or in the presence of any complication. In particular, treatment should be offered in those subclinically thyrotoxic patients with a sustained serum TSH below 0.1 U/L. However it is important to recognise that there are no large controlled intervention studies in the field and thus there is no high quality evidence to guide treatment recommendations. In particular, there is no evidence for therapy and there is weak evidence of harm from thyrotoxicosis if serum TSH is in the 0.1-0.4 IU/L range. In this review, we describe the different causes of subclinical thyrotoxicosis, and how treatment should be tailored to the specific cause. We advocate radioactive iodine treatment to be the first-line treatment in majority of patients suffering from subclinical thyrotoxicosis due to multinodular toxic goitre and solitary toxic adenoma, but we do generally not recommend it as the first-line treatment in patients suffering from subclinical Graves' hyperthyroidism. Such patients may benefit mostly from antithyroid drug therapy. Subclinical thyrotoxicosis in early pregnancy should in general be observed, not treated. Moreover, we advocate a general restriction of therapy in cases where no specific cause for the presumed thyroid hyperactivity has been proven. © 2017 European Society of Endocrinology.

Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

PubMed

Bahn, Rebecca S; Burch, Henry B; Cooper, David S; Garber, Jeffrey R; Greenlee, M Carol; Klein, Irwin; Laurberg, Peter; McDougall, I Ross; Montori, Victor M; Rivkees, Scott A; Ross, Douglas S; Sosa, Julie Ann; Stan, Marius N

2011-01-01

Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) levels in patients with overt and subclinical hyperthyroidism: effects of treatment.

PubMed

Erem, Cihangir; Civan, Nadim; Coskun, Hulya; Mentese, Ahmet; Suleyman, Akile Karacin; Altay, Diler Us; Akgul, Zeynep; Deger, Orhan

2016-06-01

Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has been shown to increase in parallel with platelet activation in acute ischaemic and thrombotic diseases. There has been no study evaluating SCUBE1 levels in patients with overt hyperthyroidism (OHyper) and subclinical hyperthyroidism (SHyper), conditions which are known to show impairment of both endothelial and platelet function. This study sought to evaluate SCUBE1 concentrations in patients with SHyper and OHyper, and assessed the effects of antithyroid drug (ATD) therapy on circulating SCUBE1 levels. Forty-five untreated patients with OHyper, 20 untreated patients with SHyper and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, SCUBE1 levels were significantly increased in patients with SHyper and OHyper (P < 0·0001 and P = 0·002, respectively). SCUBE1 levels were not significantly different in patients with OHyper compared with patients with SHyper. There was no significant correlation between serum thyroid hormones and SCUBE1 levels. Plasma SCUBE1 levels decreased significantly in both OHyper and SHyper after ATD treatment (P < 0·05). Increased SCUBE1 levels in both SHyper and OHyper patients may reflect increased platelet activation and possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. SCUBE1 may be used as a reliable marker of endothelial damage in hyperthyroidism, especially in the subclinical period. © 2015 John Wiley & Sons Ltd.

Prevention of relapse of Graves' disease by treatment with an intrathyroid injection of dexamethasone.

PubMed

Mao, Xiao-Ming; Li, Hui-Qin; Li, Qian; Li, Dong-Mei; Xie, Xiao-Jing; Yin, Guo-Ping; Zhang, Peng; Xu, Xiang-Hong; Wu, Jin-Dan; Chen, Song-Wang; Wang, Shu-Kui

2009-12-01

Antithyroid drugs are widely used in the treatment of Graves' disease (GD), but the relapse rate is very high after therapy withdrawal. We evaluated the reduction effects of intrathyroid injection of dexamethasone (IID) on the relapse rate of hyperthyroidism in patients with newly diagnosed GD. A total of 191 patients with GD completed the study. After 6 months of treatment with methimazole (MMI), the patients were randomly assigned to receive either MMI (96 patients) alone or MMI combined with IID (MMI+IID; 95 patients) treatment for 3 months, followed by continuing a dose of MMI that would maintain euthyroidism for the next 9 months in all of the patients. After withdrawal of the medical therapy, patients were followed for 24 months, and the relapse rate of hyperthyroidism was evaluated. No statistical difference was observed in the levels of serum FT(4), TSH, or TSH receptor antibodies (TR-Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at month 6. After the next 3 months of treatment with MMI+IID or MMI alone, the levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab positive rate, and thyroid volume decreased significantly in the MMI+IID group compared with the MMI group. Seven patients (7.4%) experienced a relapse of overt hyperthyroidism in the MMI+IID group and 49 patients (51%) in MMI group during the 2-yr follow-up period (P < 0.001). MMI+IID treatment is helpful to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

A 2013 European survey of clinical practice patterns in the management of Graves' disease.

PubMed

Bartalena, L; Burch, H B; Burman, K D; Kahaly, G J

2016-01-01

Management of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey. Members of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey. A total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (85·6%) and thyroid ultrasound (70·6%) to confirm aetiology, while isotopic studies were selected by 37·7%. Antithyroid drug (ATD) therapy was the preferred first-line treatment (83·8%). Compared to the previous European survey, Europeans currently more frequently use TRAb measurement and thyroid ultrasound for diagnosis and evaluation, but first-line treatment remains ATDs in a similar percentage of respondents. Current clinical practice patterns differ from those in North America, where isotopic studies are more frequently used, and radioiodine (RAI) still is first-line treatment. When RAI treatment is selected in the presence of mild Graves' orbitopathy and/or associated risk factors for its occurrence/exacerbation, steroid prophylaxis is frequently used. The preferred ATD in pregnancy is propylthiouracil in the first trimester and methimazole in the second and third trimesters, similar to North America. Significant changes in clinical practice patterns in Europe were noted compared to the previous European survey, as well as persisting differences in diagnosis and therapy between Europe and North America. © 2015 John Wiley & Sons Ltd.

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

PubMed

Peterson, Mark E

2014-11-01

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

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition).

PubMed

Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Kanamoto, Naotetsu; Otani, Hajime; Furukawa, Yasushi; Teramukai, Satoshi; Akamizu, Takashi

2016-12-30

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

Beta-adrenergic blockade for the treatment of hyperthyroidism.

PubMed

Geffner, D L; Hershman, J M

1992-07-01

To review the clinical and biochemical effects of beta-adrenergic blocking drugs on hyperthyroidism. Studies published since 1972 were identified through a computerized search of MEDLINE and extensive searching of the bibliographies of the articles identified. Based on an understanding of the differences in beta-blocker metabolism in euthyroid and hyperthyroid patients, we reviewed the differences in pharmacokinetics and metabolic and clinical outcomes during their use in hyperthyroidism, as reported in the articles reviewed. beta Blockers have been used to modify the severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20 years. The clinical efficacy of these agents is affected by hyperthyroid-induced alterations in their gastrointestinal absorption, hepatic metabolism, and renal excretion. The mechanisms whereby these clinical changes are effected is unknown. The agents differ in their beta 1 cardioselectivity, membrane-stabilizing activity, intrinsic sympathomimetic activity, and lipid solubility. They do not appear to alter synthesis or secretion of thyroid hormone by the thyroid gland. Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to triiodothyronine conversion is caused by some, but not all, beta blockers, and this appears to correlate with membrane-stabilizing activity. There does not appear to be any alteration in catecholamine sensitivity during beta-adrenergic blockade. The principal mechanism of action of beta blockers in hyperthyroidism is to antagonize beta-receptor-mediated effects of catecholamines. beta Blockers are effective in treating hypermetabolic symptoms in a variety of hyperthyroid states. Used alone, they offer significant symptomatic relief. They are also useful adjuvants to antithyroid medications, surgery, and radioactive iodide treatment in patients with Graves' disease and toxic nodular goiters.

Improved quality of life in hyperthyroidism patients after surgery.

PubMed

Bukvic, Branka; Zivaljevic, Vladan; Sipetic, Sandra; Diklic, Aleksandar; Tausanovic, Katarina; Stojanovic, Dragos; Stevanovic, Dejan; Paunovic, Ivan

2015-02-01

The most common causes of hyperthyroidism are Graves disease (GD) and toxic nodular goiter (TNG). GD and TNG might influence patients' quality of life (QoL). The aim of our study was to analyze and compare the QoL of patients with GD with that of TNG patients and to evaluate the influence of surgical treatment on their QoL. A prospective case-control study was conducted at the Center for Endocrine surgery in Belgrade, Serbia. The ThyPRO questionnaire was used in the QoL assessment of the GD and TNG patients (31 and 28, respectively) pre- and post-operatively. All patients were receiving antithyroid drugs, and none of the patients were overtly hyperthyroid at the time of completing the preoperative questionnaire. The QoL of the GD patients was worse than that of the TNG patients, with significant differences in eye symptoms, anxiety, and sex life domains (P < 0.001, P = 0.005, and P = 0.004, respectively), preoperatively, and in eye symptoms, anxiety, emotional susceptibility, and overall QoL (P = 0.001, P = 0.027, P = 0.005 and P = 0.013, respectively), postoperatively. The improvement in QoL in the GD patients was significant after surgical treatment in all ThyPRO domains. In the TNG patients, the improvement was significant in all but one ThyPRO domain, sex life (P = 0.066). The QoL of GD patients is worse than those of TNG patients. Surgery may improve QoL in patients with GD and TNG even if they have achieved satisfying thyroid status with medication treatment, preoperatively. Copyright © 2015 Elsevier Inc. All rights reserved.

[Efficacy of treatment with I(131) in paediatric Graves disease].

PubMed

Enes Romero, P; Martín-Frías, M; de Jesús, M; Caballero Loscos, C; Alonso Blanco, M; Barrio Castellanos, R

2014-01-01

Radioiodine is an important therapeutic option in young patients with Grave's disease (GD). In the United States it is a widespread therapy, but in Europe its use in paediatrics is still controversial. To report our experience in radioiodine therapy of paediatric GD patients and analyse its effectiveness and safety. We retrospectively studied our paediatric population (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I(131), side effects, and hypothyroidism rates. A total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I(131) (mean dose: 10.9±1.09 mCi). Remission with I(131) was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patients treated with I(131.) Radioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hyperthyroidism as a reversible cause of right ventricular overload and congestive heart failure

PubMed Central

Di Giovambattista, Raniero

2008-01-01

We describe a case of severe congestive heart failure and right ventricular overload associated with overt hyperthyroidism, completely reversed with antithyroid therapy in a few week. It represents a very unusual presentation of overt hyperthyroidism because of the severity of right heart failure. The impressive right ventricular volume overload made mandatory to perform transesophageal echo and angio-TC examination to exclude the coexistence of ASD or anomalous pulmonary venous return. Only a few cases of reversible right heart failure, with or without pulmonary hypertension, have been reported worldwide. In our case the most striking feature has been the normalization of the cardiovascular findings after six weeks of tiamazole therapy. PMID:18549503

A combined case of macroprolactinoma, growth hormone excess and Graves' disease.

PubMed

Hussein, Z; Tress, B; Colman, P G

2005-06-01

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

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

Xie, Fang; Fang, Cheng; School of Public Health, State University of New York at Albany, NY 12201

We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasalmore » cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels. • Dexamethasone inhibits DCBN-induced IL-6 production, but not the stem cell loss.« less

Anti-glutamic acid decarboxylase antibody in Graves' disease is a possible indicator for the unlikelihood of going into remission with antithyroid agents.

PubMed

Yoshihara, Ai; Isozaki, Osamu; Okubo, Yumiko; Takano, Kazue

2009-01-01

The prevalence and titer of glutamic acid decarboxylase antibody (GADAb) in type 1 diabetes mellitus (T1DM) has been reported to be higher in patients with autoimmune thyroid diseases (AITD) than those without them. However, we have no data about the influence of GADAb on AITD. We therefore studied the clinical characteristics of Graves' disease (GD) with GADAb in order to clarify the influence of GADAb on GD. Twelve GD patients with GADAb were enrolled and were compared to 40 GD patients without DM. The male to female ratio and age of onset of GD showed no statistical difference. The titer of TSH receptor antibody (TRAb) at the onset of GD was similar in both groups. Initial treatment with methimazole (MMI) was started in all patients with GADAb but radioactive iodine (RI) therapy was carried out in five patients because of adverse effects of MMI or poor control of hyperthyroidism. The initial titer of TRAb was significantly lower in patients treated with MMI alone compared to that in RI treated patients but none of the patients treated with MMI alone went into remission after more than 3-years of follow up. We also compared these GADAb-positive patients with 14 patients with diabetes mellitus who had matched clinical features. The number of diabetic patients who remained in possible remission was significantly higher than that of GADAb-positive patients (5 in 14 vs 0 in 12). Moreover, the rate of remission in the diabetic patients was no different from that of 21 control patients without diabetes followed for more than 7 years (5 in 14 vs 7 in 21). These data suggested that GADAb-positive patients are unlikely to go into remission with antithyroid agents. Therefore, definitive therapies might be preferable for the initial treatment of GADAb-positive patients.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

PubMed

Lim, H K; Bae, M I; Jeong, K H; Shin, M K; Lee, M-H

2016-04-01

Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV. © 2015 British Association of Dermatologists.

Left ventricular functions in children with newly diagnosed Graves' disease. A single-center study from Upper Egypt.

PubMed

Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman

2018-01-01

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

Medicinal values of fruit peels from Citrus sinensis, Punica granatum, and Musa paradisiaca with respect to alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones.

PubMed

Parmar, Hamendra Singh; Kar, Anand

2008-06-01

Peel extracts from Citrus sinensis, Punica granatum, and Musa paradisiaca were investigated for their effects on tissue lipid peroxidation (LPO) and on the concentration of thyroid hormones, insulin, and glucose in male rats. In vitro inhibition of H(2)O(2)-induced LPO in red blood cells of rats by 0.25, 0.50, 1.0, and 2.0 microg/mL C. sinensis, P. granatum, and M. paradisiaca peel extracts was observed in a dose-specific manner. Maximum inhibition was observed at 0.50 microg/mL C. sinensis, 2.0 microg/mL P. granatum, and 1.0 microg/mL M. paradisiaca. In the in vivo investigation, out of four different concentrations of each peel extract, 25, 200, and 100 mg/kg C. sinensis, P. granatum, and M. paradisiaca, respectively, were found to maximally inhibit hepatic LPO. The most effective doses were further evaluated for effects on serum triiodothyronine (T(3)), thyroxine (T(4)), insulin, and glucose concentrations. C. sinensis exhibited antithyroidal, hypoglycemic, and insulin stimulatory activities, in addition to inhibition of LPO, as it significantly decreased the serum T(4) (P < .05) and glucose (P < .001) concentrations with a concomitant increase in insulin levels (P < .05). P. granatum decreased LPO in hepatic, cardiac, and renal tissues (P < .01, P < .001, and P < .05, respectively) and serum glucose concentration (P < .01). M. paradisiaca strongly inhibited the serum level of thyroid hormones (P < .01 for both T(3) and T(4)) but increased the level of glucose (P < .05). These findings reveal the hitherto unknown potential of the tested peel extracts in the regulation of thyroid function and glucose metabolism. Besides antiperoxidative activity, C. sinensis extract has antithyroidal, hypoglycemic, and insulin stimulatory properties, which suggest its potential to ameliorate both hyperthyroidism and diabetes mellitus.

P wave duration and dispersion in patients with hyperthyroidism and the short-term effects of antithyroid treatment.

PubMed

Guntekin, Unal; Gunes, Yilmaz; Simsek, Hakki; Tuncer, Mustafa; Arslan, Sevket

2009-09-01

Prolonged P wave duration and P wave dispersion (PWD) have been associated with an increased risk for atrial fibrillation (AF). Hyperthytodism is a frequent cause of atrial fibrillation (AF). Forty-two patients with newly diagnosed overt hyperthyroidism and 20 healthy people were enrolled in the study. Transthoracic echocardiography, 12 lead surface ECG and thyroid hormone levels were studied at the time of enrollment and after achievement of euthyroid state with propylthiouracil treatment. Maximum P wave duration (Pmax) (97.4+/-14.6 vs. 84.2+/-9.5 msec, p<0.001), PWD (42.9+/-10.7 vs. 31.0+/-6.2 msec, p<0.001), deceleration (DT) (190.7+/-22.6 vs. 177.0+/-10.2 msec, p=0.013) and isovolumetric relaxation times (IVRT) (90.9+/-11.2 vs. 79.6+/-10.5 msec, p<0.001) were significantly higher in hyperthyroid patients compared to control group. Pmax and PWD were significantly correlated with the presence of hyperthyroidism. Pmax (97.4+/-14.6 to 84.3+/-8.6 msec, p<0,001) Pmin (54.1+/-8.6 to 48.1+/-8.5 msec, p=0.002), PWD (42.9+/-10.7 to 35.9+/-8.1 msec, p=0.002) and DT (190.7+/-22.6 to 185.5+/-18.3, p=0.036) were significantly decreased after achievement of euthyroid state in patients with hyperthyroidism. Diastolic dyfunction was seen in 5 patients at hyperthroid state but only in one patient at euthyroid state. Hyperthyroidism is associated with prolonged P wave duration and dispersion. Achievement of euthyroid state with propylthiouracil treatment results in shortening of P wave variables. Diastolic function may have a partial effect for the increased Pmax and PWD. Shortening of Pmax and PWD may be a marker for the prevention of AF with the anti-thyroid treatment.

Diagnostic Utility of Contrast-enhanced 3D T1-weighted Imaging in Acute Cerebral Infarction Associated with Graves Disease.

PubMed

Gon, Yasufumi; Sakaguchi, Manabu; Oyama, Naoki; Mochizuki, Hideki

2017-02-01

Graves disease is rarely complicated with cerebrovascular steno-occlusive diseases. Previous studies have suggested several hypotheses for this occurrence, including excess thyroid hormone, which stimulates the sympathetic nervous system, which in turn causes an abnormal hemodynamic response with consequent atherosclerotic changes, and antithyroid antibodies cause local vascular inflammation in patients with Graves disease. However, radiological findings of vasculitis in patients with Graves disease and cerebral infarction remain less known. We report the case of a 30-year-old Japanese woman with acute cerebral infarction due to vasculitis associated with Graves disease. She was admitted to our hospital with a 4-day history of intermittent transient dysarthria and limb shaking of the left leg when standing. Three weeks before admission, she went to a local hospital because of general malaise and was diagnosed with Graves disease. Neurological examination revealed paralytic dysarthria, left central facial nerve palsy, and left hemiparesis (manual muscle testing, 4 of 5). Blood examinations showed hyperthyroidism (thyroid-stimulating hormone ≤.010 µU/mL; free T3 ≥25.0 pg/mL; free T4 ≥8.0 ng/dL) and elevation of antithyroid antibody levels (thyroid peroxidase antibody, 87 IU/mL). The vessel wall of the right internal carotid artery was markedly enhanced on contrast-enhanced three-dimensional T1-weighted magnetic resonance imaging, suggesting vasculitis. Magnetic resonance angiography revealed right internal carotid artery occlusion after the branching ophthalmic artery. Arterial stenosis due to vasculitis was considered the cause of hemodynamic ischemic stroke. Vessel wall imaging such as high-resolution contrast-enhanced T1-weighted imaging seems useful for assessing the underlying mechanism of stroke in patients with Graves disease. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Hashimoto's thyroiditis following Graves' disease.

PubMed

Umar, Husaini; Muallima, Nur; Adam, John M F; Sanusi, Harsinen

2010-01-01

Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment.

High-fat diet affects gut nutrients transporters in hypo and hyperthyroid mice by PPAR-a independent mechanism.

PubMed

Losacco, Mariana Cerqueira; de Almeida, Carolina Fernanda Theodora; Hijo, Andressa Harumi Torelli; Bargi-Souza, Paula; Gama, Patricia; Nunes, Maria Tereza; Goulart-Silva, Francemilson

2018-06-01

High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist. HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes. We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Selenoproteins in human body: focus on thyroid pathophysiology.

PubMed

Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Antithyroid drug-associated MPO-ANCA-positive tubulointerstitial nephritis in a type 2 diabetes patient: a case report.

PubMed

Nishimura, Shinsuke; Nakao, Kazushi; Takeda, Masaya; Matsuura, Ikuko; Nomura, Yoshihisa; Shojima, Sonei; Yamamura, Yuriko; Fujita, Kazuyuki; Momoki, Noriya; Maruyama, Keisuke; Yamamura, Masahiro; Hiramatsu, Makoto

2017-05-01

A 54-year-old man diagnosed with type 2 diabetes and hyperthyroidism was prescribed propylthiouracil (PTU) after the patient developed hepatic dysfunction on thiamazole. At 50 mg/day of PTU, he was stable with thyroid-stimulating hormone receptor and thyrotropic antibody titers remaining stable. After four years of taking PTU, he was referred to the Department of Nephrology due to a rapid increase in his serum creatinine (Cr) level. He showed impaired renal function (Cr 2.26 mg/dL; estimated glomerular filtration rate (eGFR), 25 mL/min). In addition, urinary β2-microglobulin (β2 MG) was increased to 71,980 μg/L and was positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (33.9 U/mL). Gallium scintigraphy demonstrated a remarkable accumulation in both kidneys. The patient was diagnosed with tubulointerstitial nephritis based on a renal biopsy, the results of which suggested that it might have been induced by PTU. He was treated with prednisolone (PSL) at 30 mg/day. As a result, within two weeks, Cr, eGFR, and urinary β2 MG levels were progressively improved to 1.72 mg/dL, 34 mL/min, and 22,020 μg/L, respectively. Therefore, we tapered off the PSL with a dose of 5 mg/day after approximately one year. There have been no exacerbated renal function parameters. Although there are many reports on patients developing MPO-ANCA-positive crescentic glomerulonephritis after the administration of PTU, we report on a relatively rare case in which interstitial nephritis occurred after the administration of PTU.

Effect of antithyroid drug on chick embryos during the last week of development: delayed hatching and decreased cerebellar acetylcholinesterase activity.

PubMed

Haba, Gen; Nishigori, Hidekazu; Tezuka, Yu; Kagami, Keisuke; Sugiyama, Toru; Nishigori, Hideo

2011-11-01

Hypothyroid state during embryogenesis disturbs normal growth and brain development, influencing later life. To evaluate the harmful consequences of the state during embryogenesis using an animal model, we inhibited thyroid hormone biosynthesis in chick embryos by using methimazole (MMI). Typically, embryos were treated with MMI (20 µmol/egg) on day 14, and examined on specific days.  Of the control embryos, 94% hatched on day 21, whereas 0% and 60% of MMI-treated embryos hatched on days 21 and 24, respectively. MMI retarded the rates of bodyweight gain as well as liver and heart development, and delayed hatching. However, the external differences in appearance and differences in the weights of the newly hatched control chicks on day 21 and the MMI-treated chicks on day 24 were less obvious. Embryos treated with MMI exhibited increased mass in their brain parts on day 24. Most notably, the treatment resulted in a 1.35-fold increase in cerebellum weight compared to that of the untreated animals. Acetylcholinesterase activity in the cerebellum on the day of hatching decreased significantly to 0.85-fold that of the untreated controls. Thyroid hormone receptor β mRNA was detected from day 12 and dramatically expressed from day 19 to the day of hatching. The 'fertilized hen's egg-chick embryo-chick system' is an appropriate animal model for investigating the hypothyroid state during embryogenesis. Decreased cerebellar acetylcholinesterase activity after MMI treatment was assumed to relate to a mechanism of motor and cognitive deficits in congenital hypothyroidism. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Changes of Serum Angiotensin-Converting Enzyme Activity During Treatment of Patients with Graves’ Disease*

PubMed Central

Lee, Dong Soo; Chung, June-Key; Cho, Bo Youn; Koh, Chang-Soon; Lee, Munho

1986-01-01

Serum angiotensin-converting enzyme activity was measured spectrophotometrically, and serum thyrotropin-binding-inhibitory immunoglobulin (TBII) activity was measured by radioreceptor assay in normal subjects and in patients with Graves’ disease serially before and during treatment, and these activities were compared with each other and with thyroid hormone levels in various thyroid functional status. Correlation between serum angiotensin-converting enzyme activity and serum thyroid hormone level was pursued with relation to the changes of thyroid functional status in patients with Graves’ disease during treatment. Serum angiotensin-converting enzyme activity was significantly elevated in patients with hyperthyroid Graves’ disease before the start of treatment (35 ± 13 nmol/min/ml, n=50), and not in patients with Graves’ disease, euthyroid state during treatment with antithyroid drugs or radioactive iodine (23 ± 9 nmol/min/ml, n=12), but decreased significantly in patients with Graves’ disease, hypothyroid state transiently during treatment (15 ± 4 nmol/min/ml, n=12), respectively in comparison with normal control subjects. Serum angiotensin-converting enzyme activity was positively correlated with the log value of serum T3 concentration (r=0.62, p<0.001, n=95), and with the log value of free thyroxine index (r=0.66, p<0.001, n=91) but not statistically significantly with serum TBII activity. Serum angiotensin-converting enzyme activity was followed in 11 patients with initially increased activity and the activity decreased in proportion to serum thyroid hormone level during treatment, irrespective of treatment modality. It is suggested that thyroid hormones play a role in the increase and decrease of serum angiotensin-converting enzyme activity directly or indirectly influencing the peripheral tissues (probably reticuloendothelial cells or peripheral endothelial cells) in patients with Graves’ disease. PMID:15759385

Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study.

PubMed

Wang, L; Wang, B; Chen, S R; Hou, X; Wang, X F; Zhao, S H; Song, J Q; Wang, Y G

2016-09-01

The effect of selenium supplementation on recurrent hyperthyroidism caused by Graves' disease is unclear. Our study aimed to assess the efficacy of selenium supplementation therapy on recurrent Graves' disease. Forty-one patients with recurrent Graves' disease were enrolled in this study. All patients received the routine treatment using methimazole (MMI), while patients allocated to the selenium group received additional selenium therapy for 6 months. The influence of selenium supplementation on the concentrations of thyroid stimulating hormone (TSH), anti-TSH-receptor antibodies (TRAb), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed. The remission rate was also compared between 2 groups. There was no obvious difference in the demographic data and the levels of serum FT4, FT3, TSH, and TRAb between the 2 groups at baseline. Both FT4 and FT3 decreased more at 2 months in the selenium group than the controls, while the TSH level increased more in patients receiving selenium supplementation (p<0.05). The TRAb level was significantly lower in patients receiving selenium supplementation (2.4 IU/l vs. 5.6 IU/l, p=0.04). The percentages of patients with normal TRAb level at 6 months was also significantly higher in the selenium group (19.0 vs. 0%, p=0.016). Kaplan-Meier survival curve showed patients receiving selenium supplementation had a significantly higher rate of remission than controls (Log-rank test p=0.008). In conclusion, selenium supplementation can enhance the effect of antithyroid drugs in patients with recurrent Graves' disease. Randomized trials with large number of participants are needed to validate the finding above. © Georg Thieme Verlag KG Stuttgart · New York.

Preoperative management in patients with Graves' disease.

PubMed

Piantanida, Eliana

2017-10-01

Graves' disease is the most frequent cause of hyperthyroidism in iodine-sufficient geographical areas and is characterized by the presence in patients' serum of autoantibodies directed against the thyrotropin receptor (TRAb) that cause overproduction and release of thyroid hormones. Clinical presentation results from both hyperthyroidism and underlying autoimmunity. The diagnosis is based on characteristic clinical features and biochemical abnormalities. If serum thyrotropin (TSH) is low, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations should be measured to distinguish between subclinical (with normal circulating thyroid hormones) and overt hyperthyroidism (with increased circulating thyroid hormones). Graves' disease is treated with any of three effective and relatively safe initial treatment options: antithyroid drugs (ATDs), radioactive iodine ablation (RAIU), and surgery. Total thyroidectomy is favored in several clinical situations, such as intolerance, ineffectiveness or recurrence after ATD treatment, radioiodine therapy contraindicated, documented or suspected thyroid malignancy, one or more large thyroid nodules, coexisting moderate-to-severe active Graves' orbitopathy, women planning a pregnancy within 6 months. Whenever surgery is selected as treatment, selection of an expert high-volume thyroid surgeons is fundamental and careful preoperative management is essential to optimize surgical outcomes. Pretreatment with ATDs in order to promptly achieve the euthyroid state is recommended to avoid the risk of precipitating thyroid storm during surgery. For the majority of patients, euthyroidism is achieved after few weeks of ATD treatment. Beta-blockers, such as propranolol, are often added effectively to control hyperthyroid symptoms. Saturated solution of potassium iodide (SSKI) or potassium iodine (Lugol's solution), given for a short period prior to surgery, in order to reduce both thyroid hormone release and thyroid gland vascularity, is beneficial to decrease intra-operative blood loss.

Rescue pre-operative treatment with Lugol's solution in uncontrolled Graves' disease.

PubMed

Calissendorff, Jan; Falhammar, Henrik

2017-05-01

Graves' disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol's solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005-2015 and treated with Lugol's solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Twenty-seven patients were included. Lugol's solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5-9 days of iodine therapy (free T4 53-20 pmol/L, P  = 0.0002; free T3 20-6.5 pmol/L, P  = 0.04; heart rate 87-76 beats/min P  = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n  = 2, rash and vomiting n  = 1, swelling of fingers n  = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Treatment of uncontrolled hyperthyroidism with Lugol's solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol's solution could be recommended pre-operatively in Graves' disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred. © 2017 The authors.

Variation in the use of definitive treatment options in the management of Graves' disease: a UK clinician survey.

PubMed

Hookham, Jessica; Collins, Emma E; Allahabadia, Amit; Balasubramanian, Sabapathy P

2017-04-01

Graves' disease can be treated with antithyroid drugs (ATDs), radioiodine or surgery. Use of definitive treatments (radioiodine or surgery) varies widely across centres. Specific clinical circumstances, local facilities, patient and clinician preferences and perceptions will affect the choice of treatment. Detailed understanding of UK clinicians' views and their rationale for different treatments is lacking. To study the preferences and perceptions of UK clinicians on the role of surgery and radioiodine in the management of Graves' disease. 'British Thyroid Association' (BTA), 'Society for Endocrinology' (SFE) and 'British Association of Endocrine and Thyroid Surgeons' (BAETS) members were invited to complete an online survey examining their management decisions in Graves' disease and factors that influenced their decisions. 158 responses from UK consultants were included. The ratio of physicians to surgeons was 11:5 and males to females was 12:4. Most clinicians would commence ATDs in uncomplicated first presentation of Graves' disease. A wide range of risk estimates on the effectiveness and risks of treatment was given by clinicians. Radioiodine was used most frequently in relapsed Graves' disease. However, severe eye disease and pregnancy strongly influenced choice in favour of surgery. Surgeons underestimated the success of radioiodine (p<0.01) and were more likely to recommend thyroidectomy than physicians. This survey demonstrates significant variation in clinicians' perceptions of risks of treatment and their choice of management options for relapsed Graves' disease. The variation appeared to be dependent on patient and disease-specific factors as well as physician experience, gender and specialty. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism.

PubMed

Marsili, Alessandro; Ramadan, Waile; Harney, John W; Mulcahey, Michelle; Castroneves, Luciana Audi; Goemann, Iuri Martin; Wajner, Simone Magagnin; Huang, Stephen A; Zavacki, Ann Marie; Maia, Ana Luiza; Dentice, Monica; Salvatore, Domenico; Silva, J Enrique; Larsen, P Reed

2010-12-01

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T(4) to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min · mg microsomal protein, respectively, P < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T(3) in skeletal muscle physiology than previously assumed.

Type 2 Iodothyronine Deiodinase Levels Are Higher in Slow-Twitch than Fast-Twitch Mouse Skeletal Muscle and Are Increased in Hypothyroidism

PubMed Central

Marsili, Alessandro; Ramadan, Waile; Harney, John W.; Mulcahey, Michelle; Castroneves, Luciana Audi; Goemann, Iuri Martin; Wajner, Simone Magagnin; Huang, Stephen A.; Zavacki, Ann Marie; Maia, Ana Luiza; Dentice, Monica; Salvatore, Domenico; Silva, J. Enrique; Larsen, P. Reed

2010-01-01

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T4 to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min · mg microsomal protein, respectively, P < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T3 in skeletal muscle physiology than previously assumed. PMID:20881246

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues.

PubMed

Van Herck, Stijn L J; Geysens, Stijn; Bald, Edward; Chwatko, Grazyna; Delezie, Evelyne; Dianati, Elham; Ahmed, R G; Darras, Veerle M

2013-07-01

Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T₄) content but an increase in thyroidal 3,5,3'-triiodothyronine (T₃) content. This resulted in normal T₃ levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T₄ availability was only moderately affected in embryos. Peripheral T₃ levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T₃ content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T₃ content, which is reduced throughout the embryonic development period.

Hyperthyroidism secondary to hysterosalpingography: an extremely rare complication: A case report.

PubMed

Ma, Guotao; Mao, Rui; Zhai, Haixin

2016-12-01

Hysterosalpingography (HSG), a standard procedure for the evaluation of women with infertility and repetitive pregnancy loss, is associated with complications such as uterine perforation, infection, allergic reactions, syncope, hemorrhage and shock, and pulmonary or retinal embolus. However, hyperthyroidism has not been reported as one of its complications. We report the case of a 33-year-old euthyroid woman who presented to our hospital with palpitation, hand tremor, fatigue, and excessive sweating after HSG. Thyroid function tests revealed a thyroid stimulating hormone (TSH) level of 0.012 μIU/mL (range 0.38-4.34 μIU/mL), free T4 of 2.886 ng/dL (range 0.81-1.89 ng/dL), and free T3 levels of 9.4 pg/mL (range 1.80-4.10 pg/mL), and antithyroglobulin antibody of 31.78 IU/mL (range <115 IU/mL). The triiodothyronine uptake was 3.057 ng/mL (range 0.66-1.92 ng/mL). Serum iodine (SI) and urinary iodine (UI) levels: SI of 4717.748 μg/L (range 45-90 μg/L) and UI of 18069.336 μg/L (range 26-705 μg/L). The patient was diagnosed with iodine-induced hyperthyroidism (IIH), but was not treated with antithyroid drugs. She has spontaneously recovered and is pregnant currently. This is the first reported case of overt IIH caused by HSG in a euthyroid patient without risk factors. It suggests that HSG also leads to excessive iodine absorption, which induces secondary hyperthyroidism.

Spontaneous Abortion, Stillbirth and Hyperthyroidism: A Danish Population-Based Study

PubMed Central

Andersen, Stine Linding; Olsen, Jørn; Wu, Chun Sen; Laurberg, Peter

2014-01-01

Objectives Pregnancy loss in women suffering from hyperthyroidism has been described in case reports, but the risk of pregnancy loss caused by maternal hyperthyroidism in a population is unknown. We aimed to evaluate the association between maternal hyperthyroidism and pregnancy loss in a population-based cohort study. Study Design All pregnancies in Denmark from 1997 to 2008 leading to hospital visits (n = 1,062,862) were identified in nationwide registers together with information on maternal hyperthyroidism for up to 2 years after the pregnancy [hospital diagnosis/prescription of antithyroid drug (ATD)]. The Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI) for spontaneous abortion (gestational age <22 weeks) and stillbirth (≥22 weeks), reference: no maternal thyroid dysfunction. Results When maternal hyperthyroidism was diagnosed before/during the pregnancy (n = 5,229), spontaneous abortion occurred more often both in women treated before the pregnancy alone [aHR 1.28 (95% CI 1.18-1.40)] and in women treated with ATD in early pregnancy [1.18 (1.07-1.31)]. When maternal hyperthyroidism was diagnosed and treated for the first time in the 2-year period after the pregnancy (n = 2,361), there was a high risk that the pregnancy under study had terminated with a stillbirth [2.12 (1.30-3.47)]. Conclusions Both early (spontaneous abortion) and late (stillbirth) pregnancy loss were more common in women suffering from hyperthyroidism. Inadequately treated hyperthyroidism in early pregnancy may have been involved in spontaneous abortion, and undetected high maternal thyroid hormone levels present in late pregnancy may have attributed to an increased risk of stillbirth. PMID:25538898

Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress.

PubMed

Erem, Cihangir; Suleyman, Akile Karacin; Civan, Nadim; Mentese, Ahmet; Nuhoglu, İrfan; Uzun, Aysegul; Ersoz, Halil Onder; Deger, Orhan

2015-01-01

The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. Forty-five untreated patients with overt hyperthyroidism (OHyper), 20 untreated patients with subclinical hyperthyroidism (SHyper) and 30 age-and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, the levels of MDA, glucose and TG were significantly increased in patients with SHyper (p<0.05), whereas LDL-C levels were significantly decreased (p<0.01). Patients with OHyper showed significantly elevated MDA and glucose levels (p<0.001) and significantly decreased LDL-C and HDL-C levels compared with the controls (p<0.01). In patients with Graves' disease, serum TSH levels were inversely correlated with plasma MDA levels (r: -0.42, p<0.05). Plasma MDA levels significantly decreased and levels of TC, LDL-C and HDL-C significantly increased in the groups of OHyper and SHyper after treatment. Serum IMA levels did not significantly change at baseline and with the therapy in all subjects. In conclusion, increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis in these patients. Increased oxidative stress in patients with SHyper and OHyper could be improved by ATD therapy. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

PubMed Central

Bocos, Carlos; Henríquez-Hernández, Luis A.; Kahlon, Nusrat; Herrera, Emilio; Norstedt, Gunnar; Parini, Paolo; Flores-Morales, Amilcar; Fernández-Pérez, Leandro

2012-01-01

Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID:22666351

Restoration of Cardiac Tissue Thyroid Hormone Status in Experimental Hypothyroidism: A Dose-Response Study in Female Rats

PubMed Central

Weltman, Nathan Y.; Ojamaa, Kaie; Savinova, Olga V.; Chen, Yue-Feng; Schlenker, Evelyn H.; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J.

2013-01-01

Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T3 dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3-fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. PMID:23594789

Effect of double-fold surgery on spontaneous resolution of Graves' upper eyelid retraction.

PubMed

Kim, Dong Kyu; Choi, Moonjung; Yoon, Jin Sook

2015-02-01

To investigate the effect of previous incisional double-fold surgery on spontaneous resolution of eyelid retraction caused by Graves orbitopathy (GO) in Asian individuals. Retrospective review of medical records. Patients (N = 30; 39 eyes) with eyelid retraction associated with GO with symptom duration of less than 6 months. Patients who visited the Ophthalmology Department of Severance Hospital, Yonsei University, between January 2010 and December 2011, followed up for more than 6 months and in a euthyroid state with antithyroid drug treatment were included. Patients treated with steroids or who underwent surgery during follow-up were excluded. Upper scleral show was measured as the distance between the central upper lid margin and limbus at initial presentation and after 6 months. Comparative analysis was performed between the 2 groups delineated by history (n = 12; 16 eyes), or lack thereof (n = 18; 23 eyes), of incisional double-fold surgery before onset of GO symptoms and signs. Patient demographics and initial upper scleral show were not significantly different between groups. In both groups, upper scleral show significantly decreased at 6 months of follow-up (p < 0.001 in both groups); however, improvement of upper scleral show was significantly reduced in patients who had undergone previous double-fold surgery (0.8 ± 0.5 mm) than in nonsurgical patients (1.8 ± 0.5 mm; p < 0.001). Graves eyelid retraction resolves spontaneously over time, albeit not completely. Previous double-fold surgery hinders the degree of spontaneous resolution, probably because of the fibrosis and cicatrization between the skin, the subcutaneous layer, and the levator complex. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

A case of thyroid storm with a markedly elevated level of circulating soluble interleukin-2 receptor complicated by multiple organ failure and disseminated intravascular coagulation syndrome.

PubMed

Shimoda, Yoko; Satoh, Tetsurou; Takahashi, Hiroki; Katano-Toki, Akiko; Ozawa, Atsushi; Tomaru, Takuya; Horiguchi, Norio; Kaira, Kyoichi; Nishioka, Masaki; Shibusawa, Nobuyuki; Hashimoto, Koshi; Wakino, Shu; Mori, Masatomo; Yamada, Masanobu

2014-01-01

Thyroid storm (TS) is a life-threatening endocrine emergency. However, the pathogenesis of TS is poorly understood. A 40-year-old man was admitted to a nearby hospital with body weight loss and jaundice. Five days after a contrasted abdominal computerized tomography (CT) scan, he exhibited high fever and disturbance of consciousness. He was diagnosed with TS originating from untreated Graves' disease and was transferred to the intensive care unit (ICU) of our hospital. The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma scale), high fever (39.3°C), and atrial flutter with a pulse rate 162/min, and was complicated by heart failure, acute hepatic failure, and disseminated intravascular coagulation syndrome (DIC). His circulating level of soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune response, was highly elevated (7,416 U/mL, reference range: 135-483). Multiple organ failure (MOF) and DIC were successfully managed by multimodality treatments using inorganized iodide, glucocorticoids, anti-thyroid drugs, beta-blockers, and diuretics as well as an anticoagulant agent and the transfusion of platelet concentrate and fresh frozen plasma. sIL-2R levels gradually decreased during the initial treatment, but were still above the reference range even after thyroidectomy. Mild elevations in serum levels of sIL-2R have previously been correlated with thyroid hormone levels in non-storm Graves' disease. The present study demonstrated, for the first time, that circulating sIL-2R levels could be markedly elevated in TS. The marked increase in sIL-2R levels was speculated to represent an inappropriate generalized immune response that plays an unknown role in the pathogenesis of TS.

Treatment and management of thyroid storm: analysis of the nationwide surveys: The taskforce committee of the Japan Thyroid Association and Japan Endocrine Society for the establishment of diagnostic criteria and nationwide surveys for thyroid storm.

PubMed

Isozaki, Osamu; Satoh, Tetsurou; Wakino, Shu; Suzuki, Atsushi; Iburi, Tadao; Tsuboi, Kumiko; Kanamoto, Naotetsu; Otani, Hajime; Furukawa, Yasushi; Teramukai, Satoshi; Akamizu, Takashi

2016-06-01

Thyroid storm (TS) is a life-threatening endocrine emergency. This study aimed to achieve a better understanding of the management of TS by analyzing therapeutic modalities and prognoses reported by nationwide surveys performed in Japan. Retrospective analyses were performed on clinical parameters, outcomes, and treatments in 356 TS patients. Patient disease severities assessed via Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores significantly correlated with mortality. Free triiodothyronine (FT3) and the FT3/free thyroxine (FT4) ratio inversely correlated with disease severity. Methimazole (MMI) was used in the majority of patients (78·1%), and there were no significant differences in mortality or disease severity between those treated with MMI and those receiving propylthiouracil (PTU). Patients who received inorganic iodide (KI) demonstrated higher disease severity but no change in mortality compared to those who did not. Patients treated with corticosteroids (CSs) demonstrated significantly higher disease severity and mortality than those who were not. Disease severity in patients treated with intravenous administration of beta-adrenergic antagonists (AAs) was significantly higher than those treated with oral preparations, although no significant difference in mortality was observed between these groups. In addition, mortality was significantly higher in patients treated with non-selective beta-AAs as compared with other types of beta-AAs. In Japan, MMI was preferentially used in TS and showed no disadvantages compared to PTU. In severe TS, multimodal treatment, including administration of antithyroid drugs, KI, CSs and selective beta1 -AAs may be preferable to improve outcomes. © 2015 John Wiley & Sons Ltd.

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Levitsky, Lynne L

2015-01-01

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

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

PubMed

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

2018-05-13

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

Generalised pruritus as a presentation of Grave's disease.

PubMed

Tan, Ce; Loh, Ky

2013-01-01

Pruritus is a lesser known symptom of hyperthyroidism, particularly in autoimmune thyroid disorders. This is a case report of a 27-year-old woman who presented with generalised pruritus at a primary care clinic. Incidental findings of tachycardia and a goiter led to the investigations of her thyroid status. The thyroid function test revealed elevated serum free T4 and suppressed thyroid stimulating hormone levels. The anti-thyroid antibodies were positive. She was diagnosed with Graves' disease and treated with carbimazole until her symptoms subsided. Graves' disease should be considered as an underlying cause for patients presenting with pruritus. A thorough history and complete physical examination are crucial in making an accurate diagnosis. Underlying causes must be determined before treating the symptoms.

Severe pediatric Graves orbitopathy in adolescents of African origin.

PubMed

Papp, Andrea; Vasserot-Merle, Clemence; Dorner, Guido; Paridaens, Dion

2016-12-01

This article reports on two cases of severe pediatric Graves orbitopathy (GO) in two adolescents of African origin. Two black male adolescents presented with highly active GO and signs of beginning compressive optic neuropathy. Neither of them were smokers nor had a family history of GO. Besides urgent referral to pediatric endocrinologists, intravenous methylprednisolon pulse therapy was initiated. In spite of the fluctuating thyroid hormone levels in the initial phase of antithyroid therapy, intravenous steroid administration stopped the progression of malignant GO rapidly in both of our patients without any considerable side effects. Although the course of GO during childhood is considered to be mild, severe, sight threatening GO-requiring immunosuppression-may occur at young age, as in the reported adolescent patients of African descent.

Enterovirus infection--a possible trigger for Graves' disease?

PubMed

Pichler, R; Maschek, W; Hatzl-Griesenhofer, M; Huber, H; Luger, C; Binder, L; Mittermayer, H

2001-03-15

Viruses are potential environmental factors in autoimmune disease. Some evidence suggests a relationship between enteroviral infection (especially Coxsackie B virus) and autoimmunity. We investigated 21 individuals with recent onset of Graves' hyperthyroidism in regard of (subclinical) enterovirus infection. Thyrotoxic symptoms had started about two months before blood sample collection. The patients were from Upper Austria and mainly female (17/21). Their mean free thyroxin levels in blood were twice the maximum normal value and the majority achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We employed a nested PCR reaction with primers of the enterovirus genome on blood samples. All were negative for RNA of the enterovirus group. Coxsackie and related viruses were not identified as a trigger factor in autoimmune thyrotoxic disease.

Speech and language delay in two children: an unusual presentation of hyperthyroidism.

PubMed

Sohal, Aman P S; Dasarathi, Madhuri; Lodh, Rajib; Cheetham, Tim; Devlin, Anita M

2013-01-01

Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. Case reports of two children with hyperthyroidism presenting with speech and language delay. We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

Use of an iodide-specific electrode to study lactoperoxidase-catalyzed iodination of l-tyrosine.

PubMed

Threatte, R M; Fregly, M J; Field, F P; Jones, P K

1979-12-01

An in vitro method employing an iodide-specific electrode for monitoring lactoperoxidase-catalyzed iodination is described. The method utilized lactoperoxidase, potassium iodide, and a glucose--glucose oxidase system for the generation of hydrogen peroxide and l-tyrosine. As iodination of l-tyrosine proceeded, the free iodide concentration in solution decreased and was monitored by an iodide-specific electrode. The iodide electrode was reliable when compared to a 131I-method for measuring free iodide changes in solution. Increasing concentrations of resorcinol, a well-known inhibitor of thyroid peroxidase-catalyzed iodination, in the reaction mixture resulted in graded inhibition of the initial rate of lactoperoxidase-catalyzed l-tyrosine iodination. This in vitro system can be used to assess inhibitory activity of various antithyroid substances.

Wernicke-Korsakoff syndrome in the course of thyrotoxicosis - a case report.

PubMed

Wierzbicka-Chmiel, Joanna; Wierzbicki, Krzysztof; Kajdaniuk, Dariusz; Sędziak, Ryszard; Marek, Bogdan

2011-01-01

Wernicke-Korsakoff syndrome (also called Wernicke's encephalopathy) is a potentially fatal, neuropsychiatric syndrome caused most frequently by thiamine deficiency. The three classic symptoms found together are confusion, ataxia and eyeball manifestations. Memory disturbances can also be symptoms. Wernicke's encephalopathy mainly results from alcohol abuse, but also from malnutrition, cancer, chronic dialysis, thyrotoxicosis and, in well-founded cases, encephalopathy associated with autoimmune thyroid disease (EAATD). The coexistence of many factors makes a proper diagnosis difficult, delays appropriate treatment and consequently reduces the chance of complete recovery. We present the case of a 53 year-old female with Wernicke's encephalopathy caused by chronic malnutrition, surgical operation, as well as thyrotoxicosis. She received treatment with intravenous thiamine administration and also anti-thyroid treatment which caused satisfactory regression of her neurological symptoms.

High prevalence of antithyroid peroxidase and antiparietal cell antibodies among patients with type 1 diabetes mellitus attending a tertiary diabetes centre in South Africa.

PubMed

Paruk, Imran M; Ganie, Yasmeen; Maharaj, Sureka; Pirie, Fraser J; Naidoo, Vasudevan G; Nkwanyana, Ntombifikile M; Dinnematin, Hilary L; Ramdial, Pratistadevi K; Motala, Ayesha A

2017-06-01

Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B 12 , folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1 years, respectively. Mean body mass index was 21.6±6.3 kg/m 2 . GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves' disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B 12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities.

PubMed

Sgarbi, José A; Villaça, Fábio G; Garbeline, Benito; Villar, Heloísa E; Romaldini, João H

2003-04-01

Subclinical hyperthyroidism has been associated with harmful cardiac effects, but its treatment remains controversial. This study was designed to assess the cardiac effects of the normalization of serum TSH concentration in patients with endogenous subclinical hyperthyroidism. Ten patients (median age, 59 yr; range, 16-72 yr) with normal serum free T(4) and free T(3) concentration and a stable suppression of serum TSH levels were evaluated by Doppler-echocardiography, by standard and 24-h electrocardiography monitoring (Holter), and by the clinical Wayne index. Ten subjects, matched for age and sex, were used as controls. Patients were reevaluated 6 months after achieving stabilized euthyroidism by using methimazole with a median initial dose of 20 mg daily (10-30 mg daily). After reaching euthyroidism, we found a significant decrease in the heart rate (P = 0.008), the total number of beats during 24 h (P = 0.004), and the number of atrial (P = 0.002) and ventricular (P = 0.003) premature beats. Echocardiographical data resulted in a reduction of the left ventricular mass index (P = 0.009), interventricular septum thickness (P = 0.008), and left ventricular posterior wall thickness (P = 0.004) at diastole. Furthermore, the early diastolic peak flow velocity deceleration rate was significantly higher (P = 0.02) in the untreated patients compared with controls. The Wayne clinical index was higher in patients than in controls (P = 0.001) and decreased after treatment (P = 0.004). Serum TSH concentration returned to normal values after 2.5 months (range, 1.0-7.0 months) on methimazole therapy (0.05 vs. 1.42 mU/liter; P = 0.002). Serum free T(4) values were normal in patients before treatment but significantly decreased after reaching the euthyroidism (16.9 vs. 11.5 pmol/liter; P = 0.002). In contrast, serum free T(3) concentration did not differ among the groups. In conclusion, our findings support that early antithyroid therapy should be considered in patients with endogenous subclinical hyperthyroidism, where it is needed to prevent potential progression to a more advanced heart disease.

Salt-losing nephropathy in hypothyroidism.

PubMed

Bautista, Aileen Azul; Duya, Jose Eduardo De Leon; Sandoval, Mark Anthony Santiago

2014-05-21

A 35-year-old man presented with recurrent lower extremity weakness associated with polyuria later progressing to generalised weakness with difficulty in breathing. The patient was hypotensive and dry, with normal thyroid and chest examination, weak lower extremity and carpopedal spasm. Workup revealed hypokalaemia, hyponatraemia, hypocalcaemia, hypomagnesaemia, hypochloraemia and hypophosphataemia. Arterial blood gas showed respiratory alkalosis with good oxygenation. Twenty-four-hour urine collection showed normal volume with electrolyte wasting. Thyroid function test revealed overt hypothyroidism with negative antithyroid peroxidase. The patient was well after treatment with levothyroxine, volume and electrolyte replacement and was discharged. Thyroid hormones are related to the expression of the Na-K-ATPase, Na-Pi cotransporter, Mg-ATPase and Na-Ca exchanger pumps in the renal tubules. Sodium, potassium, phosphate, calcium, magnesium and water losses result from decreased expression of these pumps. 2014 BMJ Publishing Group Ltd.

Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot: case report

PubMed Central

2010-01-01

Background Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases. Case Presentation We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation. Conclusions This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important. PMID:20707932

Hyperthyroidism: Diagnosis and Treatment.

PubMed

Kravets, Igor

2016-03-01

Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extrathyroidal source. The most common causes of an excessive production of thyroid hormones are Graves disease, toxic multinodular goiter, and toxic adenoma. The most common cause of an excessive passive release of thyroid hormones is painless (silent) thyroiditis, although its clinical presentation is the same as with other causes. Hyperthyroidism caused by overproduction of thyroid hormones can be treated with antithyroid medications (methimazole and propylthiouracil), radioactive iodine ablation of the thyroid gland, or surgical thyroidectomy. Radioactive iodine ablation is the most widely used treatment in the United States. The choice of treatment depends on the underlying diagnosis, the presence of contraindications to a particular treatment modality, the severity of hyperthyroidism, and the patient's preference.

Hashimoto Thyroiditis and Nephrocalcinosis in a Child with Down Syndrome

PubMed Central

Spahiu, Lidvana; Jashari, Haki; Mulliqi-Kotori, Vjosa; Elezi-Rugova, Blerta; Merovci, Besart

2016-01-01

Introduction: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. Case Presentation: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. Conclusion: dRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications. PMID:27147809

Treatment of Graves' disease in children: The Portuguese experience.

PubMed

Marques, Olinda; Antunes, Ana; Oliveira, Maria João

2018-03-01

Graves' disease (GD) is an autoimmune thyroid disease, common in adults but rare in children. The best therapeutic approach remains controversial. To ascertain the current treatment of pediatric GD in Portugal and to assess the clinical and biochemical factors that determine definitive/long-term remission after treatment with antithyroid drugs (ATDs). A retrospective analysis of data about pediatric GD treatment collected from a nationwide survey conducted by the Portuguese Society of Pediatric Endocrinology and Diabetology from May to August 2013. Population was categorized based on sex, age, use of ATDs, dosage, treatment duration, adverse reactions, thyrotropin receptor-stimulating antibody (TRAB) titer, remission and remission/relapse rates, and definitive treatment, and divided into group A (with ongoing treatment) and group B (with treatment stopped). Group B was subdivided into 'Remission', 'Remission+relapse' and 'No remission' subgroups based on the course of disease. The same parameters were compared between both groups. Survey response rate was 77%; 152 subjects, 116 female, mean age at diagnosis 11.23±3.46 years. They all started treatment with ATDs, 70.4% with thiamazole, with a mean treatment duration of 32.38±28.29 months, and 5.9% had adverse effects. Remission rate was 32.6%. Lower age at diagnosis correlated with higher remission rates. Treatment duration was longer when propylthiouracil was used. Initial TRAB titer was significantly higher in the 'No remission' group. Surgery and radioiodine were used as second-line treatments. Our study results were similar to those reported in the literature. Age and TRAB titer were identified as potential clinical and laboratory determinants of remission. Based on risk/benefit analysis, it was concluded that treatment should be individualized based on age, accessibility to treatments, and physician's experience. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

[Epidemiological, clinical, therapeutic and evolutive aspects of Basedow-Graves disease in the Depatment of Internal Medicine at CHU Aristide Le Dantec, Dakar (Senegal)].

PubMed

Diagne, Nafissatou; Faye, Atoumane; Ndao, Awa Cheikh; Djiba, Boundia; Kane, Baidy Sy; Ndongo, Souhaibou; Pouye, Abdoulaye

2016-01-01

Basedow-Graves disease is an autoimmune affection characterized by the association of thyrotoxicosis with variable frequency events such as goiter, ophthalmopathy and pretibial myxedema. Its diagnosis is often easy, while its management remains difficult. A simple medical treatment exposes patient to recurrence risk. In Senegal and Sub-Saharan Africa few studies have focused on Basedow-Graves disease. This study aims to describe the epidemiological, clinical, therapeutic and evolutionary aspects of Basedow-Graves disease at a Hospital in Dakar. This was a retrospective study conducted from 1 January 2010 to 31 December 2013 in the Department of Internal Medicine at the Aristide Le Dantec University Hospital. During this period, 108 patients receiving outpatient treatment for Basedow-Graves disease were included out of a total of 834 patients receiving outpatient treatment. The diagnosis was made on the basis of clinical, biological and immunological signs. One hundred and eight patients suffering from Basedow-Graves disease were included out of a total of 834 consultations. Sex ratio was 7.3 and the average age was 34.6 years. The main reasons for consultation were: palpitations and weight loss in 46.3% and 39.8% of cases respectively. Thyrotoxicosis syndrome was found in 93.5% of patients, goiter was found in 87% of patients and exophthalmos in 78.7% of patients. The main complication was cardiothyreosis found in 11.1% of patients. All patients underwent antithyroid synthetic drugs treatment. The evolution was favorable in 19,4% of cases. Disease recurrence was observed in 57% of cases and in 23.1% of patients were lost to follow-up. Basedow-Graves disease is the most common cause of hyperthyroidism, The patient's clinical picture is dominated by manifestations related to hypermetabolism. This study highlights that thyroidectomy isn't the first-line of treatment if we consider the high number of recurrences after medical treatment.

Pharmacology of bovine and human thyrotropin: an historical perspective.

PubMed

Robbins, J

1999-05-01

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

Lithium toxicity and myxedema crisis in an elderly patient.

PubMed

Mir, Shahnaz Ahmad; Wani, Arshad Iqbal; Masoodi, Shariq Rashid; Bashir, Mir Iftikhar; Ahmad, Nadeem

2013-12-01

While thyroid dysfunction is a frequent complication of lithium treatment, myxedema crisis is a rare occurrence with a handful of cases described. Here, we describe a patient receiving lithium for about a decade for bipolar disorder, who presented with myxedema crisis and lithium toxicity. In this patient, myxedema crisis was likely precipitated by lithium toxicity and community acquired pneumonia. The effects of lithium on thyroid are briefly reviewed. To describe an elderly male who was diagnosed with myxedema crisis and lithium toxicity. A 70-year-old male was admitted in our hospital with history of gradual onset progressive decrease in level of consciousness and altered behavior for last 1 month. Patient also had history of respiratory tract symptoms for 1 week. Patient was a known case of diabetes and bipolar affective disorder for which he had been receiving insulin and lithium for 10 years. One year earlier, patient was admitted in our ward for glycemic control and evaluation of complications and was found to be clinically and biochemically euthyroid; he never returned for follow up until the present admission. On examination patient had incoherent speech, hypothermia, and bradycardia. Thyroid function showed thyroid-stimulating hormone >150 IU/ml, Tetraiodothyronine (T4) <1 μg/dl, anti-thyroid peroxidase titer of 60 IU/ml. The serum lithium level was 2.9 nmol/L (therapeutic level 0.2-1.2 nmol/L). He was managed with levothyroxine, starting with a loading oral dose of 500 μg through ryles tube followed by 100 μg daily, IV antibiotics and fluids; lithium was stopped after consultation with a psychiatrist. From day 5, patient started showing progressive improvement and by day 10, he had a Glasgow Coma Scale of 15/15, normal electrolyte, serum creatinine of 1.8 mg/dl and serum lithium level of 0.5 nmol/L. Lithium-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during lithium therapy and drug should be discontinued and appropriate therapy instituted if hypothyroidism develops.

Clinical Feasibility of Continuously Monitored Data for Heart Rate, Physical Activity, and Sleeping by Wearable Activity Trackers in Patients with Thyrotoxicosis: Protocol for a Prospective Longitudinal Observational Study

PubMed Central

Lee, Jie-Eun; Lee, Dong Hwa; Oh, Tae Jung; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

2018-01-01

Background Thyrotoxicosis is a common disease caused by an excess of thyroid hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis cases are caused by Graves' disease, an autoimmune disease, which has a high recurrence rate when treated with antithyroid drugs such as methimazole or propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include palpitation, weight loss, restlessness, and difficulty sleeping. Although these clinical changes in thyrotoxicosis can be detected by currently available wearable activity trackers, there have been few trials of the clinical application of wearable devices in patients with thyrotoxicosis. Objective The aim of this study is to investigate the clinical applicability of wearable device-generated data to the management of thyrotoxicosis. We are analyzing continuously monitored data for heart rate, physical activity, and sleep in patients with thyrotoxicosis during their clinical course after treatment. Methods Thirty thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul National University Bundang Hospital. Heart rate, physical activity, and sleep are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data including anthropometric measures, thyroid function test, and hyperthyroidism symptom scale are recorded. Results Study enrollment began in December 2016, and the intervention and follow-up phases are ongoing. The results of the data analysis are expected to be available by September 2017. Conclusions This study will provide a foundational feasibility trial of the clinical applications of biosignal measurements to the differential diagnosis, prediction of clinical course, early detection of recurrence, and treatment in patients with thyrotoxicosis. Trial Registration ClinicalTrials.gov NCT03009357; https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at http://www.webcitation.org/6wh4MWPm2) PMID:29467121

Triiodothyronine-predominant Graves' disease in childhood: detection and therapeutic implications.

PubMed

Harvengt, Julie; Boizeau, Priscilla; Chevenne, Didier; Zenaty, Delphine; Paulsen, Anne; Simon, Dominique; Guilmin Crepon, Sophie; Alberti, Corinne; Carel, Jean-Claude; Léger, Juliane

2015-06-01

To assess in a pediatric population, the clinical characteristics and management of triiodothyronine-predominant Graves' disease (T3-P-GD), a rare condition well known in adults, but not previously described in children. We conducted a university hospital-based observational study. All patients with GD followed for more than 1 year between 2003 and 2013 (n=60) were included. T3-P-GD (group I) was defined as high free T3 (fT3) concentration (>8.0 pmol/l) associated with a normal free thyroxine (fT4) concentration and undetectable TSH more than 1 month after the initiation of antithyroid drug (ATD) treatment. Group II contained patients with classical GD without T3-P-GD. Eight (13%) of the patients were found to have T3-P-GD, a median of 6.3 (3.0-10.5) months after initial diagnosis (n=4) or 2.8 (2.0-11.9) months after the first relapse after treatment discontinuation (n=4). At GD diagnosis, group I patients were more likely to be younger (6.8 (4.3-11.0) vs 10.7 (7.2-13.7) years) and had more severe disease than group II patients, with higher serum TSH receptor autoantibodies (TRAb) levels: 40 (31-69) vs 17 (8-25) IU/l, P<0.04, and with slightly higher serum fT4 (92 (64-99) vs 63 (44-83) pmol/l) and fT3 (31 (30-46) vs 25 (17-31) pmol/l) concentrations. During the 3 years following T3-P-GD diagnosis, a double dose of ATD was required and median serum fT4:fT3 ratio remained lower in group I than in group II. Severe hyperthyroidism, with particularly high TRAb concentrations at diagnosis, may facilitate the identification of patients requiring regular serum fT3 determinations and potentially needing higher doses of ATD dosage during follow-up. © 2015 European Society of Endocrinology.

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

PubMed Central

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

2017-01-01

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

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

COMBINATION OF MOLECULAR ADSORBENT RECIRCULATING SYSTEM AND RADIOIODINE FOR THE TREATMENT OF CONCURRENT HYPERTHYROIDISM AND SEVERE LIVER DYSFUNCTION: A RETROSPECTIVE COHORT STUDY.

PubMed

Zhang, Qing; Guan, Yanxing; Xiang, Tianxin; Liu, Shaozheng; Chen, Qingjie; Zhang, Qing

2017-02-01

The treatment of hyperthyroidism associated with severe liver dysfunction (LD) is a clinical challenge, and there has been no unified examination of this problem. The objective of this study was to assess the efficacy and safety of radioiodine ( 131 I) in combination with a molecular adsorbent recirculating system (MARS) for the treatment of hyperthyroidism complicated by severe liver LD. A total of 116 hyperthyroidism patients with concomitant LD who received MARS treatment were studied retrospectively. The patients were grouped according to whether or not they also received 131 I treatment: Group 1 (59 patients) received 131 I following MARS treatment, while Group 2 (57 cases) received only MARS. Clinical outcomes, including thyroid hormone levels, liver function parameters, and therapeutic efficacy were calculated. The overall response rate was significantly greater in Group 1 than in Group 2 (P<.01). The clinical indicators improved significantly in both groups 3 months after treatment compared with before treatment (P<.05), but Group 1 showed a greater improvement. Compared with Group 1, patients in Group 2 had a longer stay in hospital (P<.05), and received more frequent MARS treatments (P<.05). The combination of MARS and 131 I for the treatment of hyperthyroidism complicated by severe LD was effective and safe. The use of this system could rapidly improve liver function and metabolism, allowing 131 I therapy to be applied as early as possible with a shortened recovery time of liver function. ALSS = artificial liver support system ALT = alanine transaminase AST = aspartate transaminase ATD = antithyroid drugs DBil = direct bilirubin FT3 = free tri-iodothyronine FT4 = free thyroxine 131 I = radioiodine INR = international normalized ratio LD = liver dysfunction MARS = molecular adsorbent recirculating system MELD = model for end-stage liver disease PT = prothrombin time TBil = total bilirubin TSH = thyroid-stimulating hormone.

A 2011 survey of clinical practice patterns in the management of Graves' disease.

PubMed

Burch, Henry B; Burman, Kenneth D; Cooper, David S

2012-12-01

More than two decades have passed since members from the American Thyroid Association (ATA), European Thyroid Association, and Japan Thyroid Association were surveyed on management practices for patients with hyperthyroidism due to Graves' disease (GD). We sought to document current practices in the management of GD and compare these results both to those documented in earlier surveys and to practice recommendations made in the 2011 ATA/American Association of Clinical Endocrinologists (AACE) hyperthyroidism practice guidelines. Lastly, we sought to examine differences in GD management among international members of U.S.-based endocrine societies. Members of The Endocrine Society (TES), ATA, and AACE were invited to participate in a web-based survey dealing with testing, treatment preference, and modulating factors in patients with GD. A total of 730 respondents participated in the survey, 696 of whom completed all sections. Respondents included 641 TES members, 330 AACE members, and 157 ATA members. The preferred mode of therapy in uncomplicated GD was antithyroid drugs (ATDs) by 53.9% of respondents, radioactive iodine (RAI) therapy by 45.0%, and thyroid surgery in 0.7%. Compared with 1991, fewer U.S. (59.7 vs. 69%) and European (13.3% vs. 25%) respondents would use RAI therapy. Methimazole and carbimazole were the preferred ATDs, with only 2.7% of respondents selecting propylthiouracil. Patients with Graves' ophthalmopathy were treated with ATDs (62.9%) or surgery (18.5%) and less frequently with RAI plus corticosteroids (16.9%) or RAI alone (1.9%). Striking changes have occurred in the management of GD over the past two decades, with a shift away from RAI and toward ATDs in patients with uncomplicated GD. Apparent international differences persist but should be interpreted with caution. Current practices diverge in some areas from recently published guidelines; these differences should be assessed serially to determine the impact of the guidelines on future clinical practice.

Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study.

PubMed

Andersen, Stine Linding; Olsen, Jørn; Carlé, Allan; Laurberg, Peter

2015-03-01

Hyperthyroidism in women of reproductive age is predominantly caused by Graves' disease. Pregnancy associated changes in the immune system may influence the onset of disease, but population-based incidence rates in and around pregnancy have not been reported. The objective of the study was to estimate the incidence of maternal hyperthyroidism (defined by redeemed prescription of antithyroid drugs) in and around pregnancy and to compare this with the incidence of other autoimmune diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). This was a population-based cohort study. The study used the Danish nationwide registers. The participants were women who gave birth to singleton liveborn children in Denmark from 1999 to 2008 (n = 403,958). Incidence rates (IR) of maternal hyperthyroidism during a 4-year period beginning 2 years before and ending 2 years after the date when the mother was giving birth for the first time in the study period were measured. Altogether 3673 women (0.9%) were identified with an onset of hyperthyroidism from 1997 to 2010, and the overall IR of maternal hyperthyroidism was 65.0/100,000/year. The IR of hyperthyroidism in and around pregnancy varied widely and was high in the first 3 months of pregnancy [incidence rate ratio (IRR) vs the remaining study period: 1.50 (95% CI 1.09-2.06)), very low in the last 3 months of pregnancy (0.26 (0.15-0.44)], and reached the highest level 7-9 months postpartum [3.80 (2.88-5.02)]. The incidence variation in and around pregnancy was different for RA and IBD. These are the first population-based data on the incidence of hyperthyroidism in and around pregnancy. The incidence of hyperthyroidism was high in early pregnancy and postpartum, whereas such particular pattern was not observed for other diseases of autoimmune origin.

A Prospective Study on Cardiovascular Dysfunction in Patients with Hyperthyroidism and Its Reversal After Surgical Cure.

PubMed

Muthukumar, Sankaran; Sadacharan, Dhalapathy; Ravikumar, Krishnan; Mohanapriya, Gajarajan; Hussain, Zahir; Suresh, R V

2016-03-01

Cardiovascular dysfunction (CVD) is a major cause of mortality and morbidity in hyperthyroidism. CVD and its reversibility after total thyroidectomy (TT) are not adequately addressed. This prospective case-control study evaluates the effect of hyperthyroidism on myocardium and its reversibility after TT. Surgical candidates of new onset hyperthyroidism, Group A (n = 41, age < 60 years) was evaluated with 2D Echocardiography, serum n-terminal probrain natriuretic peptide (NT-proBNP) at the time of diagnosis (Point A), after achieving euthyroidism (Point B) with antithyroid drugs, and 3 months after TT (Point C). 20 patients with nontoxic benign thyroid nodules undergoing TT served as controls (Group B). Both groups were age and sex matched. Group A (n = 41) comprises Graves disease (n = 22) and Toxic Multinodular goiter (n = 19). At point A, CVD was evident in 26/41(63.4%), pulmonary hypertension (PHT) in 24/41(58.5%)--mild in 17/41(41.4%) and moderate in 7/41(17%)--dilated cardiomyopathy (DCM) in 8/41(19.5%), heart failure in 4/41(9.7%), and NT-proBNP elevated in 28/41(68.3%). At point B, recovery was observed in PHT 19/26(73.1%), DCM 4/8(50%), heart failure 4/4(100%), NT-proBNP in 3/28(10.7%). At Point C, further improvement occurred in PHT 23/24(95.8%), DCM 7/8(87.5%), heart failure 4/4(100%), and NT-proBNP in 24/28(85.7%). Pulmonary hypertension is completely reversible at 3 months after TT and is the most common cardiac event in Hyperthyroidism. Various parameters of CVD improved consistently after surgical cure. NT-proBNP levels correlated well with the severity and duration of CVD and hence can be an objective tool in monitoring of hyperthyroid cardiac dysfunction.

Hyperthyroidism caused by a germline activating mutation of the thyrotropin receptor gene: difficulties in diagnosis and therapy.

PubMed

Bertalan, Rita; Sallai, Agnes; Sólyom, János; Lotz, Gábor; Szabó, István; Kovács, Balázs; Szabó, Eva; Patócs, Attila; Rácz, Károly

2010-03-01

Germline activating mutations of the thyrotropin receptor (TSHR) gene have been considered as the only known cause of sporadic nonautoimmune hyperthyroidism in the pediatric population. Here we describe the long-term follow-up and evaluation of a patient with sporadic nonautoimmune primary hyperthyroidism who was found to have a de novo germline activating mutation of the TSHR gene. The patient was an infant who presented at the age of 10 months in an unconscious state with exsiccation, wet skin, fever, and tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain magnetic resonance imaging and computed tomography showed also Arnold-Chiari malformation type I. Continuous propylthiouracil treatment resulted in a prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months the patient underwent subtotal thyroidectomy because of symptoms of trachea compression caused by a progressive multinodular goiter. However, 2 months after surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient was treated with propylthiouracil during the next 4 years. At the age of 15 years the patient again developed symptoms of trachea compression. Radioiodine treatment resulted in a regression of the recurrent goiter and a permanent cure of hyperthyroidism without relapse during the last 3 years of his follow-up. Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline I630L mutation, which has been previously described as activating mutation at somatic level in toxic thyroid nodules. The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism. Our case report demonstrates that in this disorder a continuous growth of the thyroid occurs without any evidence of elevated TSH due to antithyroid drug overdosing. This may justify previous recommendations for early treatment of affected patients with removal of as much thyroid tissue as possible.

Thyroid function tests in patients taking thyroid medication in Germany: Results from the population-based Study of Health in Pomerania (SHIP).

PubMed

Hannemann, Anke; Friedrich, Nele; Haring, Robin; Krebs, Alexander; Völzke, Henry; Alte, Dietrich; Nauck, Matthias; Kohlmann, Thomas; Schober, Hans-Christof; Hoffmann, Wolfgang; Wallaschofski, Henri

2010-08-16

Studies from iodine-sufficient areas have shown that a high proportion of patients taking medication for thyroid diseases have thyroid stimulating hormone (TSH) levels outside the reference range. Next to patient compliance, inadequate dosing adjustment resulting in under- and over-treatment of thyroid disease is a major cause of poor therapy outcomes. Using thyroid function tests, we aim to measure the proportions of subjects, who are under- or over-treated with thyroid medication in a previously iodine-deficient area. Data from 266 subjects participating in the population-based Study of Health in Pomerania (SHIP) were analysed. All subjects were taking thyroid medication. Serum TSH levels were measured using immunochemiluminescent procedures. TSH levels of < 0.27 or > 2.15 mIU/L in subjects younger than 50 years and < 0.19 or > 2.09 mIU/L in subjects 50 years and older, were defined as decreased or elevated, according to the established reference range for the specific study area. Our analysis revealed that 56 of 190 (29.5%) subjects treated with thyroxine had TSH levels outside the reference range (10.0% elevated, 19.5% decreased). Of the 31 subjects taking antithyroid drugs, 12 (38.7%) had TSH levels outside the reference range (9.7% elevated, 29.0% decreased). These proportions were lower in the 45 subjects receiving iodine supplementation (2.2% elevated, 8.9% decreased). Among the 3,974 SHIP participants not taking thyroid medication, TSH levels outside the reference range (2.8% elevated, 5.9% decreased) were less frequent. In concordance with previous studies in iodine-sufficient areas, our results indicate that a considerable number of patients taking thyroid medication are either under- or over-treated. Improved monitoring of these patients' TSH levels, compared to the local reference range, is recommended.

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism.

PubMed

Wada, Hiromi

2017-03-01

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. Copyright © 2016 Elsevier B.V. All rights reserved.

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders

PubMed Central

Yang, Deng-Ho; Ho, Ling-Jun; Lai, Jenn-Haung

2014-01-01

During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection. PMID:24659887

Progressive Non-familial Adult onset Cerebellar Degeneration: An Unusual Occurrence with Hashimoto's Thyroiditis.

PubMed

Rao, Raghavendra S; Sheshadri, Shubha; Bhattacharjee, Dipanjan; Patil, Navin; Rao, Karthik

2018-03-13

Progressive non-familial adult onset cerebellar degeneration has been rarely associated with hypothyroidism and is known to be reversible after therapy. We report a case of cerebellar atrophy in a 31 year old female whose detailed evaluation had revealed sub-clinical hypothyroidism secondary to autoimmune thyroiditis with a very high anti-TPO (anti-thyroid peroxidase) antibody levels. MRI (Magnetic Resonanace Imaging) of brain showed diffuse bilateral cerebellar atrophy. She was treated with thyroid hormone supplementation and after one year of follow up, cerebellar signs had disappeared completely with significant reduction in anti-TPO antibody levels. Imaging of the brain post one year of follow-up revealed normal cerebellum. Hence, we opine that thyroid dysfunction should always be kept in mind while evaluating patients presenting with acute onset cerebellar ataxia as it can be easily reversed with thyroid hormone replacement therapy.

Thyroid Functions and Bipolar Affective Disorder

PubMed Central

Chakrabarti, Subho

2011-01-01

Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT) axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition. PMID:21808723

Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association

PubMed Central

Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

2015-01-01

The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS. PMID:26123455

Use of radiofrequency ablation in benign thyroid nodules: a literature review and updates.

PubMed

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation.

Use of Radiofrequency Ablation in Benign Thyroid Nodules: A Literature Review and Updates

PubMed Central

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation. PMID:24298282

Case report of Graves’ disease manifesting with odynophagia and heartburn

PubMed Central

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-01-01

Graves’ disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves’ disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment. PMID:26730171

Asymmetric chorea as presenting symptom in Graves' disease.

PubMed

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

2012-04-01

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

Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature

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

Adler, R.A.; Corrigan, D.F.; Wartofsky, L.

1976-05-01

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patientmore » with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.« less

Case report of Graves' disease manifesting with odynophagia and heartburn.

PubMed

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-12-28

Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

Bone mineral density trends in Indian patients with hyperthyroidism--effect of antithyroid therapy.

PubMed

Dhanwal, Dinesh Kumar; Gupta, Nandita

2011-09-01

Hyperthyroidism is associated with bone loss, which is reversible after treatment. The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment especially at forearm is not clear. Therefore, the present study was conducted to assess degree of reversibility in bone mineral density following one-year medical treatment in Indian patients with hyperthyroidism. A total of 30 consecutive patients with hyperthyroidism were included in this one year study at All India Institute of Medical Sciences, New Delhi, India. All the patients were assessed for parameters of bone mineral homeostasis such as calcium, phosphorous, alkaline phosphatase, 25-hydroxy vitamin D [25 (OH) D], parathyroid hormone (PTH) at the time of diagnosis and after one year medical treatment. Bone mineral density was measured using Hologic DXA scan at hip, spine and forearm. All the patients received medical therapy with carbimazole. The parameters of bone homeostasis and bone mineral density at base line and after one year medical treatment was compared. All patients attained euthyroid status after eight weeks of carbimazole therapy. Parameters of bone homeostasis such as calcium, phosphorous, 25 (OH) D and PTH did not show any significant change from base line. Bone mineral density expressed as bone mineral content in gm/cm2 at left hip neck, trochanteric and intertrochanteric region was significantly higher after carbimazole therapy (745.2 +/- 127.6 gm/cm2 vs. 688.2 +/- 123.5 gm/cm2; p = 0.02, 573.4 +/- 109.9 gm/cm2 vs. 641.0 +/- 138.0 gm/cm2, p = 0.005 and 1008.6 +/- 185.5 gm/cm2 vs. 938.0 +/- 145.3 gm/cm2 p = 0.0131 respectively). Bone mineral density at lumbar spine expressed as either T and Z score was significantly higher after treatment (10 months of euthyroid state) (-0.6 +/- 1.3 vs. -1.7 +/- 1.2, p = 0.013 and -0.4 +/- 1.2 vs. -1.4 +/- 1.2, p = 0.012 respectively). However Bone mineral measures as T and Z score at left forearm decreased significantly after one year of medical therapy. In Indian patients with hyperthyroidism, the pattern of recovery of bone loss after one year of antithyroid therapy suggests early recovery at hip and lumbar spine and deterioration at forearm.

Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies

PubMed Central

Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

2017-01-01

Abstract Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE. We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20–83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92% for both). Tumors were not identified in any cases. All patients responded to immunotherapy or spontaneously remitted, thereby fulfilling the criteria of HE. This study demonstrated that LE associated with anti-NAE antibodies is a nonparaneoplastic LE and various limbic symptoms that depend on the onset type. Favorable therapeutic efficacy suggests that this LE can be considered a clinical subtype of HE and that anti-NAE antibodies may be a promising indicator of the need for immunotherapy. PMID:28272206