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To clarify the actual administration of thiamazole (MMI), the first choice of antithyroid drugs, the actual therapy provided by the Japan Thyroid Association (JTA) members for the following conditions was surveyed. The subjects included adult patients, pregnant women, and pediatric patients with Graves' disease who visited each medical institution from September 2019 to February 2020. Initial doses, frequency of administration, maintenance doses, maximum doses, consultation intervals for pregnant women, and dosages administrated to breastfeeding mothers were surveyed. The total number of cases collected was 11,663. Administration of 15 mg once a day was the most common initial therapy, constituted 74.4% (2,526/3,397 cases) of adults, 33.8% (44/130) of pregnant women, and 50.8% (61/120) of children. The maintenance dose before discontinuation was equivalent to 2.5 mg/day in 52.3% (3,147/6,015). The most common maximum dose for adults and children was 30 mg/day, administrated to 57.5% of adults (223/388) and 59.6% (28/47) of children; for pregnant women, it was 15 mg/day, administrated to 71.1% (27/38). The most common consultation interval for pregnant women was every four weeks (32.1%, 341/1,063). In lactating mothers, the dose was 10 mg/day or less in 366 of 465 cases (78.7%). Breastfeeding was also allowed 4-6 hours after the administration of 15-20 mg/day in 69 patients (14.8%). Breastfeeding was prohibited in 26 patients (5.6%). In conclusion, initial MMI therapy was started with 15 mg once a day in most patients, and MMI was also administrated to lactating mothers following the Graves' disease treatment guidelines by the JTA.

Hyperthyroidism is a common disease mainly manifested by hyperexcitability of multiple systems and hypermetabolism. Currently, antithyroid drugs (ATDs), radioiodine therapy (RIT), and surgery are mainly used in the clinical treatment for primary hyperthyroidism. We reported a case of a 28-year-old female who received a novel treatment for primary hyperthyroidism. This patient had poor control of thyroid function while taking ATD, and her oral Methimazole (MMI) dose varied repeatedly between 20 mg qd and 15 mg qd, failing to maintain a stable status. To minimize the possible complication and to achieve drug reduction or withdrawal, she refused RIT and surgery and showed up in our department. The patient, diagnosed with Graves’ disease (GD) and met the surgical indication after systematic clinical evaluation, was subject to ultrasound-guided percutaneous microwave ablation (MWA) of the partial thyroid gland with continuous oral administration of 20 mg qd MMI. The post-ablation condition was stable and the patient was discharged 2 days after the operation. Thyroid ultrasound and serum thyroid function test were examined regularly after ablation and the MMI dosage was gradually reduced according to the results of the biochemical examination. Five weeks after the operation, the patient completely discontinued the medication. Ultrasound-guided percutaneous microwave ablation is minimally invasive, safe, and effective, and has potential to be an alternative treatment besides the 3 classical treatments of hyperthyroidism.

Objective Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. Methods This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. Results Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P Conclusions Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

Objective Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design Participants with newly diagnosed Graves’ disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire “competence” for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.

Background: The prognosis of Graves' disease (GD) is reportedly related to sex, age, and genetic factors, although there is no consensus. The objective of this study was to investigate the relation...

Objective Comparison of studies on remission rates in pediatric Graves’ disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves’ disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis. Methods PubMed and Embase were searched in August 2020 for studies on patients with Graves’ disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis. Results Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5–2.5 years, 2.5–5 years, 5–6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%). Conclusions Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Background Painless thyroiditis (PT) is characterized by transient hyperthyroidism with a low Tc-99m uptake. We herein describe 11 cases of PT that occurred during treatment with potassium iodide (KI) for Graves' disease (GD). Patients and Method From August 2016 to December 2018, 11 women with GD who developed PT during treatment with KI were enrolled. Of these patients, 10 discontinued antithyroid drug (ATD) because of side effects and began KI, and 1 patient switched from thiamazole to KI because she was planning a pregnancy. The mean patient age was 40.1 years old. Thyroid function tests, thyroid autoantibodies including anti thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb), and M22-TRAb, and the 99mTc uptake were evaluated at the time of PT. Results All 11 women patients presented with transient thyrotoxicosis in which 99mTc scans revealed a low uptake of 0.34% ±0.15% (normal 0.70%-1.02%). M22-TRAb was absent in all cases except for one (2.4 IU/L), whereas TgAb and TPOAb were present in 10 and 6 cases, respectively. Ten patients returned to a euthyroid status without passing through the post-hypothyroid phase, and one patient underwent total thyroidectomy during the euthyroid phase of PT. Only four patients require beta-blocker therapy. All patients with KI-induced PT except 1 displayed GD remission during a mean observation period of 23.3 months, and 1 patient had recurrence of GD after PT. Conclusion We encountered 11 GD patients who developed PT during treatment with KI, which was initiated after ATD had been discontinued due to side effects.

Objectives\ud\udThe risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy.\udMethods\ud\udWe searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity.\udResults\ud\udWe identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06–1.54) and PTU (RR, 1.16; 95% CI, 1.08–1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01–1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14–1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up.\udConclusions\ud\udATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.

Background Whole-body oxidative stress can be estimated by the urine excretion of oxidized guanosine species, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), derived from RNA and DNA, respectively. These oxidative stress markers are not well explored in thyroid disorders. Objective We aimed to determine whether treatment of hyperthyroid patients affects the levels of these oxidative stress markers. Methods Urinary excretion of 8-oxoGuo and 8-oxodG was measured in 51 hyperthyroid patients (toxic nodular goiter [TNG], n = 30; Graves disease [GD], n = 21) before or shortly after initiation of therapy and when stable euthyroidism had been achieved for at least 12 months. Results Adjusting for age, the baseline urinary excretion of oxidative stress markers correlated positively with plasma thyroxine (8-oxoGuo, P = 0.002; 8-oxodG, P = 0.021) and was significantly higher in GD than in TNG patients (P = 0.001 for both oxidative stress markers). Restoration of euthyroidism significantly affected the excretion of the oxidative stress markers. In TNG, 8-oxoGuo decreased from geometric mean 2.11 nmol/mmol creatinine (95% CI, 1.85-2.39) to 1.91 nmol/mmol (95% CI, 1.67-2.19; P = 0.001), while 8-oxodG decreased from 1.65 nmol/mmol (95% CI, 1.41-1.93) to 1.48 nmol/mmol (95% CI, 1.27-1.74; P = 0.026). In GD, 8-oxoGuo decreased from 2.25 nmol/mmol (95% CI, 1.95-2.59) to 1.79 nmol/mmol (95% CI, 1.63-1.97; P = 0.0003), while 8-oxodG decreased from 2.02 nmol/mmol (95% CI, 1.73-2.38) to 1.54 nmol/mmol (95% CI, 1.31-1.81; P = 0.001). In the euthyroid state, there were no differences between groups. Conclusion Restoration of euthyroidism in patients with hyperthyroidism significantly decreased the systemic oxidative stress load by 10% to 25%. Our findings may help to explain the higher morbidity and mortality linked to hyperthyroid diseases, as shown in observational studies.

Objective Radioiodine has been increasingly used to treat hyperthyroidism for many years. Although widely regarded as an effective therapy, radioiodine treatment for hyperthyroidism has been suspected to be associated with the risk of mortality. This study aimed to quantify the mortality outcomes in patients who were treated for hyperthyroidism with radioiodine. Methods Systematic search and meta-analysis were performed to determine the risk of mortality in patients treated with radioiodine for hyperthyroidism. Relevant studies were searched through August 2020 and selected in accordance with the inclusion criteria. Results A total of 13 studies were identified. The summary odds ratios (ORs) showed an increased risk of all-cause mortality in patients who were treated with radioiodine for hyperthyroidism (OR = 1.20; 95% CI = 1.07-1.35). The risk of death attributed to all forms of circulatory, respiratory, and endocrine and metabolic diseases was significantly increased, with summary ORs of 1.23 (95% CI, 1.12-1.35), 1.43 (95% CI, 1.17-1.75), and 2.38 (95% CI, 1.85-3.06), respectively. The summary ORs revealed no significant association between radioiodine treatment for hyperthyroidism and the risk of cancer mortality (OR = 1.03; 95% CI, 0.98-1.09). Radioiodine treatment for hyperthyroidism was not associated with the risk of mortality from breast, respiratory system, gastrointestinal, and genitourinary cancers. Conclusion Radioiodine treatment for hyperthyroidism is associated with the risk of all-cause mortality but not cancer mortality. Future research needs to address the causes of hyperthyroidism, effects of radioiodine therapy, and potential effects of confounding to identify causality.

Background: This study aimed to compare the effectiveness and safety of radioiodine (RAI) and long-term methimazole (MMI) in the treatment of subclinical hyperthyroidism (SH) in the elderly. Method...

Background Glucocorticoid treatment is used in children with Graves’ disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). Conclusions The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

A 29-year-old woman was diagnosed with Graves' disease because of her symptoms of thyrotoxicosis. After a 15-day treatment with methimazole, she began to suffer from a repeated fever, rash, and polyarticular migratory arthralgias. The clinical examination on admission showed that her white blood cell count, neutrophil count, and erythrocyte sedimentation rate (ESR) were within normal limits, while the concentration of C-creative protein (CRP) was 26.14 mg/L (ref. 0 - 10) and anti-nuclear immune body (ANA) and anti-neutrophil cytoplasmic antibody (ANCA) were both negative. Upon stopping the drug treatment, the patient's symptoms promptly disappeared. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. Furthermore, physician's awareness of this syndrome is essential for its diagnosis in clinical practice.

Background Long-term antithyroid drug therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years. Methods Fifty nine patients with Graves’ disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years. Results Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study. Conclusions Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research. Trial registration IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143.

Background Graves' disease (GD) is a clinical autoimmune thyroid disease. During the treatment of GD, antithyroid drug‐induced agranulocytosis (TIA) is a common and even life‐threatening adverse drug reaction. Previous studies suggested that susceptibility to TIA is strongly associated with HLA‐B*27:05, HLA‐B*38:02, and HLA‐DRB1*08:03 genetic variation and six single nucleotide polymorphisms (SNPs) in MICA genes. Aims The purpose of this study is to further study the associations between TIA, HLA‐B and MICA. Materials & Methods We genotyped MICA‐STR and MICA‐129 variants in 41 TIA and 308 control patients with GD and investigated the linkage effect among SNPs and short tandem repeat (STR) of MICA and HLA‐B alleles. Results The results showed that MICA*A5.1 was significantly associated with TIA (p = .007, odd ratio = 1.958, 95% confidence interval, 1.192–3.214). In addition, high linkage among MICA‐129 and six SNPs MICA and HLA‐B was detected, and two haplotypes (AAAACAAAAACGGCCTA and AACAAAAAAAACATTAA (p = 5.14E−07 and p = 3.42E−08, respectively)) were significantly associated with TIA. Furthermore, when we analyzed only MICA‐129 and HLA‐B separately, the haplotypes (AAAACAAAAAA with p = 2.49E−07 and AACAAAAAAAA with p = 2.14E−09) were identified with more significant effects. MICA‐129 was completely linked to six SNPs with haplotypes ACATTACA (p = 2.05E−05) significantly associated with TIA. Conclusion These data indicated that there was a significant linkage effect between MICA‐129 and other alleles, suggesting that they exert interactive effects as risk factors for the development of TIA., Our manuscript indicated that there was a significant linkage effect between MIA*A5.1, MICA‐129, and other loci, suggesting that they exert interactive effects as risk factors for the development of GD‐TIA.

Background Stickler syndrome is a connective tissue disorder with predominantly autosomal dominant inheritance, with ocular, auditory and joint involvement. Thyroid dysfunction was not described as part of alterations in Stickler syndrome and in particular, the association between Stickler’s syndrome and Graves’ disease has never been previously reported in literature. Moreover, the presence of Graves’ disease is uncommon in the pediatric age (especially in children younger than 6 years old). Case presentation We report the case of a 5-years old child affected by Stickler syndrome who received the diagnosis of Graves’s disease, in absence of suggestive symptoms, during health supervision. Conclusions This is the first evidence of thyroid dysfunction and autoimmune pattern for Sticker syndrome. Further clinical reports are expected before suggesting the implementation of new clinical skills for Stickler syndrome, but this paper may contribute to improve personalized management of this rare disorder.

OBJECTIVE A suboptimal quality of life (QoL) has been reported in patients with Graves' disease treated in adult life, but long-term QoL in those treated in childhood and adolescence is unclear. We wanted to understand how Graves' disease and its management impact on the physical, psychological and social well-being of young people and their longer-term QoL. DESIGN, PATIENTS AND MEASUREMENTS Two questionnaires were used to assess QoL and patient experience of Graves' disease; PedsQL™ Generic Core Scales and a Graves' disease questionnaire devised for this project. The anonymized questionnaires were sent to young people (

We report the case of a 42-year-old male patient with acute onset of asymmetrical polyarthritis of the medium and large joints as well as fever and elevated serological inflammation markers. The symptoms began shortly after initiation of thiamazole treatment for newly diagnosed Graves' disease. Antithyroid arthritis syndrome (AAS) is a rare but serious adverse side effect of antithyroid treatment with thioamides such as thiamazole. Clinically, AAS may present with myalgia, arthralgia, fever, exanthema and polyarthritis. In the case of suspected AAS, when possible the thionamide medication should be rapidly discontinued or modified in consultation with the endocrinologist. In some cases anti-inflammatory therapy with NSAID or corticosteroids may be required for symptom control.Wir berichten über den Fall eines 42-jährigen Patienten mit akuter asymmetrischer Polyarthritis der großen und mittelgroßen Gelenke sowie Fieber und erhöhten serologischen Entzündungszeichen. Die Symptomatik begann kurz nach Beginn einer Thiamazol-Therapie bei neu diagnostiziertem Morbus Basedow. Eine durch Thionamide ausgelöste Arthritis wird auch als „antithyroid arthritis syndrome“ (AAS) bezeichnet und ist eine seltene unerwünschte medikamentöse Nebenwirkung. Klinisch kann sich das Krankheitsbild mit Myalgien, Arthralgien, Fieber, Hautausschlag und Polyarthritis präsentieren. Bei Verdacht auf ein AAS sollte die Thionamid-Medikation in Rücksprache mit dem Endokrinologen nach Möglichkeit zeitnah abgesetzt oder umgestellt werden. In einigen Fällen ist eine antiinflammatorische Therapie mit NSAR oder Glukokortikoiden zur Symptomkontrolle nötig.

Objective: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment. Methods: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure. Results: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P 3 months was also associated with treatment failure (P = .002). Conclusion: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

Background: None of the current therapeutic approaches for management of Graves' disease has been able to re-establish normal thyroid function in all patients. Objective: To describe the author's 35 years of personal experience in the management of Graves' hyperthyroidism and, in doing so, review current articles published on the long-term medical treatment of hyperthyroidism. Methods: All published articles related to ≥4 years of continuous antithyroid drug (ATD) treatment were searched. Findings were added and compared with studies published by the authors on the same topic. Results: Long-term ATD treatment is effective and safe, both in children and adults, for treatment of hyperthyroidism. Treatment of Graves' patients with ATDs >60 months causes euthyroidism up to 4 years after discontinuation of ATDs in the majority of patients. Long-term ATD therapy is not inferior to radioiodine therapy and may sometimes even be superior in some aspects, when considering serum lipid profile, cardiac function, mood, and cognition. Conclusions: Long-term ATD therapy for Graves' hyperthyroidism is efficient and safe and induces control of hyperthyroidism, without rendering the patient hypothyroid in the majority of patients.

We aimed to assess the ankle-brachial index (ABI) in patients with Graves’ disease. In the cross-sectional assessments, 81 patients with drug-naïve Graves’ disease and 235 with euthyroidism were enrolled. ABI and vascular cell adhesion molecule-1 (VCAM-1) levels were assessed. In the prospective follow-up, 32 patients with Graves’ disease were assessed again after antithyroid drugs for at least 4 weeks, and 32 age- and sex-matched controls with euthyroidism were also followed up. Patients with Graves’ disease had a higher VCAM-1 level (1309 ± 292 vs. 1009 ± 168 ng/mL, P

Background The epidemiology and natural history of autonomously functioning thyroid nodules (AFTNs) have not been elucidated. Here we report the pregnant Japanese woman with an AFTN. Case presentation The patient was a 31-year-old woman who was hospitalized due to the placenta previa associated with threatened abortion at the 16 weeks of her third pregnancy. At her second pregnancy, she was euthyroid but had a single, 2.3 cm nodule on her right thyroid lobe. Her thyroid hormone level was trended increased with her pregnancy progression, and the thyrotoxic state was remained after delivery. Before her third pregnancy, her hyper-vascular nodule enlarged to 3.4 cm at regular monitoring. When she visited our hospital, she was at 16 weeks of pregnancy and had thyrotoxicosis with negative TSH-receptor antibody. She delivered a baby weighing 2615 g without hypothyroidism at 39 weeks of pregnancy by natural delivery. After delivery, a 99mTc scintigram showed a hot spot in her right thyroid lobe. She was diagnosed with AFTN and treated with methimazole while nursing. Conclusions This case showed that hCG stimulation during pregnancy caused thyroid nodule enlargement and enhanced thyroid hormone production. The pregnancy could be the pathological stimulus and provides chance to diagnosis for AFTNs.

Background Mechanical ventilation (MV) is life saving; yet it may induce severe lung injury and lead to multisystem organ failure and death. Thyroid hormones (THs) promote alveolar fluid clearance and alleviates hypoxia-induced lung injury. Given that the mechanism involved in hypoxia-induced lung injury is different from that of ventilator-induced lung injury, we examined the effects of thyroid function on lung extravascular fluid (LF), aquaporin 5 (AQP 5) expression, and alveolar viscoelasticity (AVE) in mechanically ventilated rat. Methods Hypothyroid (hypo) and hyperthyroid (hyper) animals were generated by administration of metimazole and L-thyroxine, respectively. Lung injury was induced by high-tidal volume MV. The LF was estimated by lung wet weight-to-dry weight ratio assessment. Expression of AQP 5 was evaluated by western blotting and in situ immunohistochemistry. The AVE was judged by elastic lung pressure/volume curve recording. Results Injurious MV significantly reduced lung AQP 5 expression and altered LF and AVE in a thyroid function–dependent manner. Regardless of animals' ventilation mode, hyper state caused significant reductions in LF and lung AQP 5 protein. It also improved AVE irrespective of animals' ventilation mode. The effects of hypo condition on LF, AQP 5 expression, and AVE were in contrast to that of hyper state. Conclusions These data indicate that thyroid function has profound effects on LF, AQP 5, and AVE in mechanically ventilated lungs. Given that the effects of thyroidal status were as prominent as that of injurious MV, we suggest that thyroid function should be considered when patients are to be subjected to MV.

Objective Thyroid disorders including hyperthyroidism are common during pregnancy. Untreated hyperthyroidism can result in adverse outcomes for pregnancy. Methods Iodine, propylthiouracil (PTU), carbimazole (CMZ), and methimazole (MMI) are common medications for hyperthyroidism treatment. The literature regarding antithyroid medication use in pregnancy and breastfeeding is reviewed. Results Animal studies for PTU have suggested congenital anomalies while animal studies for MMI have only indicated adverse outcomes at higher doses than used in humans. Epidemiological studies have noted an increased risk of congenital anomalies for PTU less often than CMZ or MMI but the epidemiological evidence remains mixed. A pattern of anomalies has been described for CMZ and MMI, from both case and epidemiological studies, including choanal atresia, aplasia cutis congenita, and other facial, heart, gastrointestinal, and skin anomalies. Closer examination of cases indicates that a few cases of the anomalies have occurred without exposure to CMZ or MMI and outside of the proposed critical period. PTU has a small risk of hepatotoxicity which rarely results in liver transplantation and death. Some authors have suggested that PTU be prescribed in early pregnancy and switched to MMI in late pregnancy. Untreated hyperthyroidism, from either a lack of medications or switching medications during the first trimester, may also increase the chance of congenital anomalies. Multiple case studies and larger epidemiological studies have failed to provide clear, consistent outcomes for the use of PTU, CMZ, and MMI in pregnancy. MMI and PTU both enter the breastmilk in small amounts. Conclusion Additional research is needed to assist in the medical management and exposure counseling of pregnant and breastfeeding women with hyperthyroidism.

Introduction: Occurrence of pancytopenia in patients with untreated hyperthyroidism is extremely rare. To the best of our knowledge, only 30 cases have been reported in the English literature. Accurate diagnosis and appropriate tailored therapy are challenging due to the variegated causes of pancytopenia and the potential hematological toxicity of antithyroid drugs (ATDs). Case report: We present a 51-year-old Caucasian man with newly diagnosed Graves’ disease showing pancytopenia and liver dysfunction. Although in this context the use of ATDs is still under debate, low-dose methimazole therapy was able to induce resolution of both pancytopenia and liver dysfunction, along with euthyroidism restoration. Conclusion: Searching in the English literature for previous studies, we identified only 30 cases worldwide to form our database. A demographic as well as clinical, laboratory, and histopathological analysis was performed. In most cases, the recovery of biochemical euthyroidism through the use of ATDs induced the resolution of pancytopenia (at laboratory and histological levels). Our review provides clinical, laboratory, and histopathological features of Graves’s hyperthyroidism-related pancytopenia with a view to improving the knowledge of this rare hematological complication and assisting in the decision-making process regarding therapeutic options.

To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland.All of 117 juvenile patients (25 males and 92 females, aged 10 to 18lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximumAt the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses ofOver a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD.ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy

Thionamide-induced agranulocytosis (TIA), namely antithyroid drug (ATD)-induced agranulocytosis, is one of the most feared adverse effect of ATDs. It is defined as a granulocyte count of less than 0.5 × 109/L after ATD administration. Several studies reported that TIA is associated with human leukocyte antigen (HLA) and nearby genes. Our previous study found that the susceptibility genes of TIA are similar in north China and European populations. We evaluated the associations of 23 candidate single nucleotide polymorphisms (SNPs) in 37 patients with TIA and 254 patients with Graves’ disease (GD) as controls by iPLEX MassARRAY system. Five SNPs in the MHC class I polypeptide-related sequence A(MICA) genes [rs4349859 (p = 1.43E-7); rs145575084 (p = 5.79E-6); rs116135464 (p = 3.70E-5); rs148015908 (p = 3.79E-5) and rs189600525 (p = 2.15E-4)] were found to be significantly associated with TIA after Bonferroni correction. After combining with previous data of rs4349859 and HLA-B*27:05, the haplotype analysis showed that patients carrying P-A-C-A-T-T-A haplotype have a higher risk of TIA (p = 9.76E-7; OR = 14.85, 95% CI 3.63–60.77). Our findings suggest that five high linked SNPs of MICA gene are significantly associated with susceptibility to TIA.

Objective: To analyze the effects of methimazole (MMI)-containing combination regimens on the thyroid status and relapse rates in patients with Graves hyperthyroidism (GH) using a network meta-analysis to provide guidance for clinical application. Methods: We conducted a literature review, which identified 21 trials for inclusion. The major outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. The secondary outcome was relapse rate. A network meta-analysis was used to compare multiple regimens to identify the most advantageous regimen. Results: The types of combined drugs included anti-oxidant complexes, selenium, vitamin D3, cholestyramine, risedronate, iodine, potassium bromide, immunosuppressants, and β-adrenergic antagonists. Regarding the FT3 results, the rank probability of the best result showed that potassium bromide (0.897) and vitamin D3 (0.833) had relative advantages in reducing FT3 at the 1-month time point. According to the time trend analysis, compared with the control treatment, cholestyramine and iodine showed advantages in reducing FT3 during the early stage (0 to 3 months). The immunosuppressants showed advantages in reducing FT3 during the late stage (>9 months) but not the early stage. Regarding the FT4 results, potassium bromide had the highest P-score (.965) at the 1-month time point. Iodine and cholestyramine had advantages in reducing FT4 during the early stage. The immunosuppressants had advantages during both the early and late stages. Conclusion: MMI combined with cholestyramine or iodine was shown to regulate serum FT3 and FT4 during the early stage of GH. MMI combined with immunosuppressants had a long-term advantage in FT3/FT4 regulation and reduced the relapse rate. Abbreviations: ATD = antithyroid drug; CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = Graves hyperthyroidism; MMI = methimazole; OR = odds ratio; RCT = randomized controlled trial; SMD = standard mean difference; TCM = traditional Chinese medicine.

The oral treatment of feline hyperthyroidism with antithyroid drugs often results in gastrointestinal side effects (10-20%). To date only oral formulations are approved although the oral application is not tolerated by all cats. Transdermal therapy can be an alternative. Nanocarriers could be used to ensure adequate transport of active agents through the skin. The present pilot study investigated the efficacy and safety of a novel dermal formulation of thiamazole for the treatment of feline hyperthyroidism. For the first time, amphiphilic dendritic core-multishell-nanocarriers were used. Cats with T4 values ≥ 4.0 µg/dl or a T4 value from 3.0-4.0 µg/dl and defined clinical findings were recruited. The euthyroid range for the T4 value was defined from ≥ 0.8 and ≤ 4.0 µg/dl. A total of 24 hyperthyroid cats were included and treated with thiamazole ointment for three weeks (24 cats) up to eight weeks (12 cats). The treatment success was 50% after three weeks and 41,7% after eight weeks. Cats that were within the euthyroid range required after three weeks a mean total dose of 1,09 mg/kg/d (0,68-1,7 mg/kg/d, 12/24) and after eight weeks 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). No side effects were observed during the three resp. eight-week study period. Variations of the T4 value in companion cats in the same household were comparable to those of an independent control group. Thiamazole ointment based on nanocarriers is suitable for the treatment of feline hyperthyroidism.Bei der oralen medikamentösen Behandlung der felinen Hyperthyreose mit Thyreostatika kommt es bei 10–20% der Katzen zu gastrointestinalen Nebenwirkungen. Aktuell sind ausschließlich orale Formulierungen zugelassen, wobei nicht alle Katzen eine orale Medikamentengabe tolerieren. Eine Alternative kann die transdermale Therapie sein, bei der ein Wirkstofftransport über die Haut durch Nanocarrier gewährleistet wird. In der vorliegenden Pilotstudie wurde die Wirksamkeit und Sicherheit einer neuartigen dermalen Formulierung von Thiamazol zur Behandlung der felinen Hyperthyreose untersucht. Zum Einsatz kamen erstmals amphiphile dendritische Kern-Multischalen-Nanocarrier. Eingeschlossen wurden Katzen mit einem Serum- T4-Wert ≥ 4,0 µg/dl oder einem T4-Wert zwischen 3,0–4,0 µg/dl und festgelegten klinischen Befunden. Der euthyreote Bereich wurde mit einem T4-Wert zwischen ≥ 0,8 und ≤ 4,0 µg/dl definiert. Insgesamt wurden 24 hyperthyreote Katzen eingeschlossen und drei (24 Katzen) bis acht Wochen (12 Katzen) mit Thiamazolsalbe behandelt. Der Behandlungserfolg lag nach drei Wochen bei 50%, nach acht Wochen bei 41,7%. Die Katzen, die den euthyreoten Bereich erreichten, erhielten nach drei Wochen eine mittlere Dosis von 1,09 mg/kg/d (0,68–1,7 mg/kg/d, 12/24) bzw. nach acht Wochen 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). Während des drei bzw. achtwöchigen Studienzeitraumes konnten keine Nebenwirkungen beobachtet werden. Die Schwankungen der T4-Werte von im selben Haushalt lebenden Partnerkatzen waren mit denen einer unabhängigen Kontrollgruppe vergleichbar. Die auf Nanocarriern basierende Thiamazolsalbe ist zur Behandlung der felinen Hyperthyreose geeignet.Le traitement oral de l’hyperthyroïdie féline avec des médicaments antithyroïdiens entraîne souvent des effets secondaires gastro-intestinaux (10 à 20% des cas). À ce jour, seules les formulations orales sont approuvées, bien que l’application orale ne soit pas tolérée par tous les chats. La thérapie transdermique peut être une alternative. Des nanoporteurs pourraient être utilisés pour assurer un transport adéquat des agents actifs à travers la peau. La présente étude pilote a examiné l’efficacité et l’innocuité d’une nouvelle formulation cutanée de thiamazole pour le traitement de l’hyperthyroïdie féline. Pour la première fois, des nanoporteurs à noyau multicellulaire dendritiques amphiphiles ont été utilisées. Des chats avec des valeurs T4 ≥ 4,0 µg/dl ou une valeur T4 de 3,0–4,0 µg/dl et un tableau clinique définis ont été recrutés. La gamme euthyroïdienne pour la valeur T4 a été définie entre ≥ 0,8 et ≤ 4,0 µg/dl. Un total de 24 chats hyperthyroïdiens ont été inclus et traités avec une pommade au thiamazole pendant une période allant de trois semaines (24 chats) jusqu’à huit semaines (12 chats). Le succès du traitement était de 50% après trois semaines et de 41,7% après huit semaines. Les chats qui se trouvaient dans la gamme euthyroïdienne avaient besoin après trois semaines d’une dose totale moyenne de 1,09 mg/kg/j (0,68–1,7 mg/kg/j, 12/24) et après huit semaines 1,65 mg/kg/j (1,49-2,04 mg/kg/j, 5/12). Aucun effet secondaire n’a été observé pendant les trois respectivement les huit semaines de l’étude. Les variations de la valeur T4 chez les chats vivant dans le même ménage étaient comparables à celles d’un groupe témoin indépendant. La pommade au thiamazole à base de nanoporteurs convient au traitement de l’hyperthyroïdie féline.Il trattamento orale dell’ipertiroidismo felino con farmaci tirostatici causa nel 10-20% dei gatti degli effetti collaterali gastrointestinali. Attualmente sono approvate solo delle formulazioni orali anche se non tutti i gatti tollerano un medicamento per via orale. Un’alternativa sarebbe una terapia transdermica che garantisce via dei nanovettori il trasporto del principio attivo attraversa la pelle. In questo studio pilota è stata studiata l’efficacia e la sicurezza di una nuova formulazione dermica con tiomazolo per il trattamento dell’iperdiroidismo nei felini. Per la prima volta si sono utilizzati nanovettori anfifilici dendritici con nucleo a più gusci. Sono stati presi in considerazione solo gatti con risultati clinici accertati e con un valore sierico T4 ≥ 4,0 µg/dl oppure con un valore T4 tra 3,0–4,0 µg/dl. La zona eutiroidea è stata definita con un valore T4 compreso tra ≥ 0,8 e ≤ 4,0 µg/dl. Sono stati inclusi un totale di 24 gatti ipertiroidei e sono stati trattati con un unguento al tiomazolo durante 3 (24 gatti) a otto settimane (12 gatti). Il successo del trattamento dopo tre settimane era del 50% e dopo otto settimane del 41.7%. I gatti che hanno raggiunto la zona eutiroidea avevano ricevuto dopo tre settimane una dose media di 1,09 mg/kg/d (0,68–1,7 mg/kg/d, 12/24) e dopo otto settimane 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). Non sono stati rilevati effetti collaterali durante il periodo dello studio di tre a otto settimane. Le variazioni dei valori T4 tra gatti partner che vivevano nella stessa famiglia erano paragonabili a quelle di un gruppo di controllo indipendente. L’unguento a base di tiomazolo con nanovettori è adatto al trattamento dell’ipertiroidismo felino.

Graves' disease is uncommon in children. The remission rate after antithyroid drugs (ATD) therapy is lower than in adults. We evaluated the clinical course of ATD therapy in children with Graves' disease in southern Taiwan to determine whether their biochemical markers could be used to predict remission in these patients. We retrospectively reviewed the clinical data of 53 children diagnosed with Graves' disease between 2009 and 2019. Clinical and biochemical parameters were analyzed for predictors of remission. About three‐fourths of the patients were female. Their median age at diagnosis was 13 years. No sex differences were found in most clinical characteristics. There was no correlation between thyroid‐stimulating hormone receptor antibody (TRAb) levels at diagnosis and thyroid function or adverse reactions to ATD. Relapse occurred in 62% of patients after discontinuation of first‐course ATD therapy. Three variables—good initial response to ATD, a decrease in TRAb levels during the first year after diagnosis, and a decrease in TRAb levels during the second year after diagnosis—were significant predictors of remission for more than 18 months. In conclusion, children with Graves' disease who had early ATD‐controlled Graves' disease and decreased TRAb levels during the first 2 years are likely to enter remission for more than 18 months.

Introduction: First-line treatment for most young people with Graves' disease (GD) will include the administration of a thionamide antithyroid medication (ATD); Carbimazole (CBZ), Methimazole (MMZ), or rarely, propylthiouracil (PTU). GD is a challenge for families and clinicians because the likelihood of remission following a course of ATD is lower in young people when compared to adults, yet the risk of adverse events is higher. An overall consensus regarding the optimal ATD treatment regimen is lacking; how ATD are prescribed, for how long and how the associated risk of adverse events is managed varies between clinicians, units and nations. This partly reflects clinician and family uncertainty regarding outcomes.Areas covered: This review will focus on some of the key articles published in the field of thionamide ATD in children. It will highlight key issues that need to be discussed with families as well as addressing the approach and controversies in the treatment of GD. This article does not reflect a formal systematic review of the literature.Expert opinion: New strategies in areas such as immunomodulation may see the development of new antithyroid drug treatments that, either in isolation or in combination with thionamide therapy, may increase the likelihood of long-term remission.

Before us is the story of young woman who actively monitored the condition of the thyroid gland, due to the accidental detection of antibodies to the thyroid tissue. After the detection of a tumor (7 mm), hemi thyroidectomy was conducted. For two years after the operation she has been under the care of oncologist and endocrinologist. However, despite explanations about a good prognosis of the disease, she is extremely alarmed and unjustifiably often conducts laboratory tests, ignoring the fact that both the reference range and the evaluation methods are different. It should be said that similar problems exist in all countries (Nedman C. et al., 2017) fear of relapse of the disease worries the vast majority of patients even years after its been diagnosed. People are concerned not only about the risks of thyroid cancer recurrence, but also about the risks of development of other cancers, the risks of being not able to get access to skilled care. The obvious task of a doctor is to correct a pattern of patient behavior that increases anxiety.

A patient with underlying Hashimoto's thyroiditis developed amiodarone-induced thyrotoxicosis type 1 that was successfully treated using methimazole in combination with potassium iodide. A 35-year-old woman admitted for perinatal care of twin-to-twin transfusion syndrome was given amiodarone for 7 days for paroxysmal ventricular contraction following pulseless ventricular tachycardia 1 day after delivery. She developed thyrotoxicosis one month after the discontinuation of amiodarone therapy and was negative for thyroid-stimulating hormone receptor antibody. An increased peak velocity of the superior thyroid artery suggested amiodarone-induced thyrotoxicosis type 1. Her thyroid function recovered after combination therapy with methimazole and potassium iodide.

Purpose of review This review is intended to highlight recent studies which provide new data on the epidemiology and management of children with hyperthyroidism, including neonates. Recent findings A French study demonstrates differences in age-related trends in incidence of hyperthyroidism in males versus females and suggests the overall incidence may be increasing. New studies confirm the effectiveness and safety of long-term medical therapy (up to 10 years), including from the first randomized trial of short-term versus long-term therapy. Radioiodine ablation (RAI) is the main alternative therapy, though surgery may have some advantages if done in a high-volume center; using higher weight-based doses of I-131 (250 μCI/g thyroid tissue) could increase proportion of patients achieving hypothyroidism and decrease repeat ablations. Maternal or neonatal thyroid-stimulating hormone (TSH) receptor antibodies in children of mothers with Graves' disease, and TSH at 3-7 days of age are good predictors of which neonates will have problems. Summary More research is needed on the epidemiology of Graves' disease. Long-term medical therapy well past two years should be considered an option in compliant patients to decrease the number who need definitive therapy. For those receiving RAI, a dose of about 250 μCI/g thyroid tissue should result in fewer cases of persistent hyperthyroidism than lower doses.

We report a 74-year-old man with a 2-year history of proximal limb pain, body weight loss of 15 kg, and muscle weakness. Muscle atrophy was evident in the limbs and trunk, as well as the tongue. He was admitted to our hospital with suspected amyotrophic lateral sclerosis (ALS). Although he had no physical manifestations of Basedow disease such as palpitations, hyperhidrosis, hand tremor, exophthalmos, and an enlarged thyroid, he was diagnosed as having thyrotoxic myopathy as laboratory examinations indicated hyperthyroidism and positivity for TSH receptor antibody. The serum level of soluble IL-2 receptor was also elevated. Despite the severe muscle atrophy, the serum CK level was normal. A biopsy from the left quadriceps muscle revealed Type 1 fibers atrophy. Administration of anti-thyroid drugs normalized his thyroid function and the level of soluble IL-2 receptor, leading to improvement of the generalized muscle atrophy.

Background Thyroid storm is a rare, life-threatening disease triggered by an acute event or trauma, such as surgery of the thyroid or another area, and infection. However, recent studies have shown that irregular use or discontinuation of antithyroid drugs is the most common cause of thyroid storm. A cardiovascular event caused by thyroid storm following coronary artery bypass graft (CABG) is high output heart failure with extreme tachycardia, which can be fatal. Thyroid storm after nonthyroidal surgery, especially CABG, has been rarely reported, with only one reported case until now. Herein, we present a case of thyroid storm onset in a patient who underwent CABG. Case presentation A 74-year-old woman with a history of antithyroid medication discontinuation against medical advice underwent urgent CABG. The patient exhibited extreme tachycardia postoperatively, which is highly suggestive of thyroid storm. Although a higher infection risk is an important consideration, a high-dose steroid was used to control the intractable tachycardia that did not respond to beta-blocker administration. Despite appropriate antibiotic treatment, the patient’s condition was exacerbated, and she developed multiple organ failure resulting from adult respiratory distress syndrome progression, and she died on day 8 after surgery. Conclusions Risk factors for thyroid storm after CABG and its treatment outcomes are rarely reported. Patients with a history of inappropriate antithyroid medication prescription should be in a euthyroid state before surgery. If surgery is imminent, anticipating thyroid storm and its treatment as well as a euthyroid state can improve recovery outcomes postoperatively.

The treatment of Graves' hyperthyroidism (GD) complicated with malignancy is challenging, as anti-thyroid thionamide drugs (ATDs) and anti-cancer chemotherapy are both associated with a risk of neutropenia. Treatment with conventional ATDs, radioactive iodine (RAI) or potassium iodide (KI) was attempted in 8 patients with malignancy (34-80 years of age; 2 males and 6 females) in whom GD had been fortuitously diagnosed during a detailed systematic examination. Three patients requiring surgery were initially treated conventionally with methylmercaptoimidazole (MMI), MMI and KI or RAI (group A; one patient each). The patients became euthyroid on days 17-31 and underwent surgery on days 25-47. RAI therapy was administered to one patient after surgery. The patients were then treated with KI during chemotherapy. Five other patients who did not require surgery were initially treated with 100 mg KI monotherapy (group B). The serum free T4 level declined immediately in all of these patients, and they became euthyroid on days 7-18, remaining almost entirely euthyroid for more than 120 days. Anti-cancer chemotherapy was successfully completed for three of the patients while taking KI, despite the patients experiencing repeated episodes of anti-cancer chemotherapy-induced neutropenia. Our present findings suggest that, in patients with GD and malignancy, MMI + KI or RAI may be required if immediate surgery is scheduled, but KI monotherapy may be worth trying, if anti-cancer chemotherapy is scheduled, thus avoiding the possibility of thionamide-induced neutropenia.

Background The remission rate in children with Graves' disease (GD) after 2-6 years of antithyroid drug (ATD) treatment is 40-50%. It has been reported that it is difficult to predict the GD prognosis based on the TSH receptor antibody (TRAb) level at the cessation of ATD treatment. We studied whether the persistence of negative TRAb at ATD treatment cessation increased the remission rate in pediatric patients with GD. Methods We included 22 patients diagnosed with GD who discontinued ATD treatment after confirmation of negative TRAb on two or more consecutive tests. Remission was defined as the maintenance of normal thyroid function, including serum TSH level, with negative TRAb more than 2 years after ATD discontinuation. Results Of the 22 patients, 12 achieved remission (remission rate 54.5%), with no significant between-group difference in the median duration of ATD treatment in the remission and relapse groups (4.4 vs 3.9 years). Of the 10 patients who relapsed, 4 (40.0%) relapsed within 2 years after ATD discontinuation, and 4 (40.0%) relapsed more than 5 years after ATD discontinuation. Conclusions The persistence of negative TRAb at ATD treatment cessation might indicate prolonged duration of remission but does not increase the final remission rate in patients with childhood-onset GD.

Context Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). Objective We explored whether rituximab (RTX), a B-lymphocyte–depleting agent, would increase remission rates when administered with a short course of ATD. Methods This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A’Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3′-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. Results A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A’Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. Conclusion Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

BackgroundOptimal treatment for persistent Graves’ disease following 12–18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.MethodsThis retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.ResultsThere were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60–4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20–1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38–1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend < 0.001).ConclusionsIn patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves’ disease.

Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined.

Background Rash and cholestatic liver injury caused by methimazole (MMI) in patients with Turner syndrome (TS) and Graves’s disease (GD) are rarely reported, and there is a paucity of reports on the management of this condition. It is not clear whether propylthiouracil (PTU) can be used as a safe alternative in this case. Case presentation: A 37-year-old woman was admitted to our hospital with rash, severe pruritus and a change in urine colour after 2 months of GD treatment with MMI. Physical examination showed rash scattered over the limbs and torso, mild jaundice of the sclera and skin, short stature, facial moles, immature external genitals and diffuse thyroid gland enlargement. Liver function tests indicated an increase in total bilirubin, direct bilirubin, total bile acid, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. The level of sex hormones suggested female hypergonadotropic hypogonadism. The karyotype of peripheral blood was 46, X, i(X)(q10)/45, X. After excluding biliary obstruction and other common causes of liver injury, combined with rash and abnormal liver function following oral administration of MMI, the patient was diagnosed as having TS with GD and rash and cholestatic liver injury caused by MMI. MMI was immediately discontinued, and eleven days after treatment with antihistamine and hepatoprotective agents was initiated, the rash subsided, and liver function returned to nearly normal. Because the patient did not consent to administration of 131I or thyroid surgery, hyperthyroidism was successfully controlled with PTU. No adverse drug reactions were observed after switching to PTU. Conclusions While patients with TS and GD are undergoing treatment with MMI, their clinical manifestations, liver functions, and other routine blood test results should be closely monitored. When patients with TS and GD manifest adverse reactions to MMI such as rash and cholestatic liver injury, it is necessary to discontinue MMI and treat with antihistamine and hepatoprotective agents. After the rash subsides and liver function returns to nearly normal, PTU can effectively control hyperthyroidism without adverse drug reactions.

Introduction The treatment strategies for a 42‐year‐old female index patient with moderate Graves’ disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. Materials and Methods From a Swedish cohort of 1186 GD patients (TT‐12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This ‘index patient cohort’ was age 40–45, otherwise healthy female, with two children and uncomplicated GD. The applied first‐line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT‐12 cohort was also performed. Results In the ‘Index cohort’, 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (131I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where 131I was preferred. The distribution of treatment in the TT‐12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19–22) patients, as was RAI in old (age 69–73) patients. The age‐related, but not the gender‐related, cases differed significantly from the entire TT‐12 cohort. Conclusion The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where 131I is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from ‘real life’ has been presented and compared to treatment preferences of international thyroid association surveys., According to several international surveys, the treatment strategies for a 42‐year‐old female index patient with moderate Graves’ disease vary considerably. In this study, the correlation of treatment strategies between patients from the Swedish thyrotoxicosis 2012 study cohort, who met the criteria for the index patient and its variations, and the theoretical index patient in international surveys is examined and compared. This is in order to allow a reasonable comparison with and, if possible, to validate the international surveys.

Purpose: The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism. Methods: Articles were searched through the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and QVIP. The primary outcomes were clinical efficacy and thyroid hormone levels in MMI and PTU groups. The secondary outcomes were liver function indexes and adverse reactions in MMI and PTU groups. Results were expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The Begg test was applied to assess the publication bias. Results: Totally, 16 randomized controlled trials were retained in this meta-analysis with 973 patients receiving MMI and 933 receiving PTU. The levels of triiodothyronine (T3) (WMD = −1.321, 95% CI: −2.271 to −0.372, P = .006), thyroxine (T4) (WMD = −37.311, 95% CI: −61.012 to −13.610, P = .002), Free T3 (FT3) (WMD = −1.388, 95% CI: −2.543 to −0.233, P = .019), Free T4 (FT4) (WMD = −3.613, 95% CI: −5.972 to −1.255, P = .003), and the risk of liver function damage (OR = 0.208, 95% CI: 0.146–0.296, P

BackgroundThyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia.MethodsAn institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared atp ResultsMean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89–38.16,p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04–7.15,p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning β-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery.ConclusionsIn developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.

Background/purposeGraves’ disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. There is some debate regarding the optimal treatment and predicting factors of remission or relapse in children and adolescents with GD. In this study, we report a retrospective study of 195 children and adolescents with GD treated at a single tertiary institution in Korea.MethodsThis study included children and adolescents with GD diagnosed before 19 years of age from January of 2000 to October of 2020. The diagnosis of GD was based on clinical features, high thyroxine (FT4), suppressed thyroid-stimulating hormone, and a positive titer of thyrotropin receptor antibodies. Remission was defined as maintenance of euthyroid status for more than six months after discontinuing antithyroid drug (ATD).ResultsA total of 195 patients with GD were included in this study. The mean age at diagnosis was 12.9 ± 3.2 years, and 162 patients (83.1%) were female. Among all 195 patients, five underwent thyroidectomy and three underwent radioactive iodine therapy. The mean duration of follow-up and ATD treatment were 5.9 ± 3.8 years and 4.7 ± 3.4 years, respectively. The cumulative remission rates were 3.3%, 19.6%, 34.1%, 43.5%, and 50.6% within 1, 3, 5, 7, and 10 years of starting ATD, respectively. FT4 level at diagnosis (P = 0.001) was predicting factors for remission [HR, 0.717 (95% CI, 0.591 – 0.870), P = 0.001]. Methimazole (MMI)-related adverse events (AEs) occurred in 11.3% of patients, the most common of which were rash and hematologic abnormalities. Of a total of 26 AEs, 19 (73.1%) occurred within the first month of taking MMI.ConclusionsIn this study, the cumulative remission rate increased according to the ATD treatment duration. Long-term MMI treatment is a useful treatment option before definite treatment in children and adolescents with GD.

Purpose This review focuses on the results of prospective randomized clinical trials and the conclusions from respective meta-analyses in order to summarize experiences with adjuvant selenium (Se) supplementation in Graves’ hyperthyroidism and orbitopathy, while identifying ambiguous findings and highlighting important open research issues. Methods We searched the PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through May 31, 2019, for relevant studies. Results The available evidence concerning routine use of Se in the treatment of Graves’ hyperthyroidism remains ambiguous. Results of meta-analyses, including ten RCTs, suggest that adjuvant Se supplementation can enhance the restoration of biochemical euthyroidism. Unfortunately, these results must be judged cautiously owing to several important limitations. Moreover, an in-depth analysis of relevant long-term clinical measures of therapeutic success (such as remission rate after antithyroid drug treatment), besides surrogate markers (for example, hormone or autoantibody concentrations), is generally missing. Based on a single study, Se supplementation is recommended in patients with mild orbitopathy of short duration because it may decrease inflammation and eye-specific symptoms while also achieving a marked improvement in disease-specific quality of life. The effects of Se supplementation on moderate-to-severe orbitopathy remain as yet unknown. Conclusions Additional randomized clinical trials with clinically relevant endpoints are urgently needed to further aid in clinical decision-making, including better stratification of Graves’ disease patients, who are most likely to benefit from Se supplementation.