Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study.

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.

Apathetic Graves' disease with severe hepatic and renal dysfunction induced by COVID-19 infection: Case report and literature review.

RATIONALE: A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic. PATIENT CONCERN: A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month. DIAGNOSIS: Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy. INTERVENTION: Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy. OUTCOME: After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later. CONCLUSION: COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.

Plasmapheresis in thyrotoxicosis: a single-center case series.

BACKGROUND: Plasmapheresis represent an alternative therapeutic option for hyperthyroidism with thyroid storm or refractory cases. It provides a rapid decrease in plasma thyroid hormones and anti-thyroid antibodies. The aim of this paper was to report our single center's experience in managing particular situations of hyperthyroidism using apheresis. CASES PRESENTATION: The following case series describes three young African patients (two females, one male) aged 29, 37, and 25 years old, respectively, with Graves' disease who presented with drug ineffectiveness, drug-induced agranulocytosis, and thyroid storm with multi-organ failure. The three patients underwent plasmapheresis sessions leading to effective decline of thyroid hormone levels and offering a window for processing total thyroidectomy. DISCUSSION/CONCLUSION: The standard management of thyrotoxicosis and thyroid storm was usually codified by the concomitant use of antithyroid medication, iodine, beta-blockers, and corticosteroids. This medical preparation can be effective in most cases. However, drug toxicity or ineffectiveness can limit the use of such therapeutics. Our paper supports the efficiency and safety of therapeutic plasma exchange in the preoperative management of thyrotoxicosis.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Effects of block-replace regimen in patients with autoimmune hypothyroidism converted to Graves' disease.

PURPOSE: We present two cases of autoimmune hypothyroidism converted to Graves' disease (GD) and their medical management. METHODS: We tested thyroid function and thyroid antibodies and performed an ophthalmologic examination and neck ultrasound in two patients with autoimmune hypothyroidism converted to GD during a follow-up of several years. CASE REPORTS: The first case is a 33 year-old woman with hypothyroidism due to Hashimoto's thyroiditis (HT). She developed signs and symptoms of hyperthyroidism after 7 years of treatment with the same dose of levothyroxine (LT4). Even when LT4 therapy was discontinued, she remained thyrotoxic, with mild Graves' ophthalmopathy (GO) and very high thyroid-stimulating hormone receptor antibodies (TRAb > 40 IU/L, reference range: <1.75 IU/L). Antithyroid medication was started on a titration regimen, without achievement of euthyroidism. She was switched to a block and replace regimen, using 20 mg of methimazole (MMI) and 75 mcg of LT4 daily, with normalization of thyroid hormones and improvement of GO without steroids. The second case is a 57 year-old man with a 2-year positive medical history of HT and 6 months of LT4 treatment. He developed hyperthyroidism and moderate-severe GO. Despite stopping LT4 and initiating antithyroid medication in a titration regimen, he did not achieve euthyroidism and had active GO. Pulse glucocorticoid therapy and switching to a block-replace regimen was required to achieve euthyroidism and reduce ocular proptosis and diplopia. CONCLUSION: Spontaneous autoimmune conversion of hypothyroidism to hyperthyroidism can occur at any time: it is important to promptly identify these cases so as to manage them effectively.

Cardiovascular sequelae of hyperthyroidism: A rare case report of thyrotoxic cardiomyopathy.

INTRODUCTION: This case report highlights a distinctive presentation of cardiovascular sequelae arising from hyperthyroidism, shedding light on a rarely observed condition within the medical literature. The unique aspects of this case contribute valuable insights to our understanding of the intricate relationship between thyroid dysfunction and cardiac complications. CLINICAL PRESENTATION: The patient exhibited a constellation of symptoms, including palpitations, weight loss, and anxiety, indicative of hyperthyroidism. Notably, a thorough clinical examination revealed critical cardiovascular findings, such as elevated heart rate, arrhythmias, and signs of heart failure, underscoring the significant cardiac implications associated with this disorder. DIAGNOSIS AND INTERVENTIONS: Following a comprehensive diagnostic process, the patient was diagnosed with thyrotoxic cardiomyopathy, a rare manifestation of hyperthyroidism characterized by cardiac muscle dysfunction. Therapeutic interventions encompassed a multidisciplinary approach involving antithyroid medications, beta-blockers, and supportive heart failure management. The intricate connection between thyroid function and cardiac performance necessitated tailored treatment strategies. OUTCOMES: A notable improvement in the patient's clinical status was observed throughout treatment. Reduction in heart rate, resolution of arrhythmias, and amelioration of heart failure symptoms collectively underscored the efficacy of the chosen interventions. This case report emphasizes the importance of prompt and accurate diagnosis and a comprehensive treatment regimen in achieving positive clinical outcomes in patients with thyrotoxic cardiomyopathy. CONCLUSION: This case is a poignant reminder of the interplay between endocrine and cardiovascular systems. The unique presentation of thyrotoxic cardiomyopathy in the context of hyperthyroidism expands our knowledge of potential cardiovascular sequelae. Clinicians are urged to consider such intricate connections and remain vigilant for atypical cardiac manifestations in patients with thyroid dysfunction. Timely intervention and tailored management strategies are paramount in mitigating the impact of these rare yet clinically significant conditions.

Case report: Severe cholestatic jaundice associated with hyperthyroidism treated with methimazole.

RATIONALE: We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment. PATIENT CONCERNS: The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases. DIAGNOSIS: The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out. OUTCOMES: The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function. LESSONS: The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

Effect of iodine nutritional status on the recurrence of hyperthyroidism and antithyroid drug efficacy in adult patients with Graves' disease: a systemic review.

Aim: To probe the appropriate iodine nutritional status for patients with Graves'disease (GD) hyperthyroidism and on antithyroid drugs (ATD) or after drugwithdrawal. Method: Studies were retrieved from three databases (Embase, Medline, and Cochrane Library) and were screened and evaluated using predefined criteria. The risk of bias of each trial was assessed using a tool from Cochrane. The iodine nutritional status of the subjects was redefined according to the World Health Organization (WHO) criteria and classified as insufficient/adequate/above requirements/excessive iodine intake. Result: Two randomized controlled trials (RCTs) and 3 observational studies were selected from the 376 retrieved papers, which had different degrees of risk of bias in study design. The heterogeneity among them prevented us from further synthesizing effect indicators and subsequent statistical analyses. Two RCTs with high quality showed that insufficient or above requirements iodine intake was detrimental for ATD-treated GD patients; adequate iodine intake was associated with a lower risk of recurrence and better efficacy in controlling thyrotoxicosis. It could be speculated from three low-quality observational studies that excessive iodine intake may be associated with higher (or similar) recurrence rates and lower remission rates compared to above requirements iodine intake in these patients, but none of them could answer the question of the effect of insufficient or adequate iodine intake on this issue. Conclusion: Although the available evidence is suboptimal, this systematic review tentatively suggests that in adult patients with GD hyperthyroidism receiving ATDs and according to WHO criteria for iodine nutritional status, adequate iodine intake is associated with a lower recurrence rate, a higher remission rate and a better efficacy to control thyrotoxicosis than insufficient, above requirement, or excessive iodine intake. Future RCTs with large samples are expected to elucidate the actual impact of different iodine nutritional statuses on the recurrence rate of hyperthyroidism and the efficacy of ATD to control thyrotoxicosis in these patients. Systematic review registration: identifier CRD42022359451.

Acute Thyrotoxic Myopathy Combined with Neck Pain: A Case Report.

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.

Different doses of methimazole treatment of children and adolescents with graves' disease: a clinical study based on 161 cases of outpatients.

OBJECTIVE: This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD. METHODS: One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed. RESULTS: After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%). CONCLUSIONS: Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

The management of pediatric Graves' disease.

PURPOSE OF REVIEW: Graves' disease (GD) constitutes a significant proportion of thyroid disorders seen during childhood. Several specialties may be closely involved in the management of pediatric patients with GD and emerging research in each field contributes to variations in the approach over time. Here we review the recent literature on the management of the disease, with the hope that this can be a valuable resource for treating specialists who need to be continuously updated on new data obtained in relevant fields. RECENT FINDINGS: Genetic, postinfectious and environmental factors may play a role in the immunological pathophysiology of GD. Research performed during the COVID-19 pandemic supports that viral-induced immune dysregulation may be a possible trigger for the disease. The various current treatment options all have positive and negative factors to consider. Antithyroidal drug therapy (ATD) is generally recommended as the initial treatment, although remission rates are only 20-30% at 2 years and 75% at 9 years. Unfortunately, about half of patients will relapse within 1 year of discontinuing therapy. Radioactive iodine therapy (RAI) is an effective treatment option and can be considered in certain pediatric patients. There continues to be no definitive evidence that the doses used for GD lead to a higher risk of cancer. Surgical treatment via thyroidectomy is effective and safe when performed by a high-volume surgeon. Recent studies show improvement in quality-of-life after surgery in adolescents and young adults. Future medical treatment options for GD currently being studied include antigen-specific immunotherapy and monoclonal antibodies. SUMMARY: Although the future holds promising new therapeutic options for autoimmune diseases including GD, the current choices continue to be ATD, usually first-line, and definitive treatments including RAI and surgery. While all three offer the possibility of remission or cure, drug therapy and RAI have a possibility of relapse. Risks of each approach should be broached in detail with patients and their families, and the nuances of treating this disease specifically in children should be familiar to all treating providers.

What is the impact of stress on the onset and anti-thyroid drug therapy in patients with graves' disease: a systematic review and meta-analysis.

BACKGROUND: The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease. METHODS: Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis. RESULTS: Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (ß = 0.22, P < 0.01) and weaker in studies with older patients with GD (ß =-0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09). CONCLUSIONS: The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.

The Origin of Antithyroid Drugs.

Background: When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has been learned about their mechanism of action and clinical utility, they continue to be used today in much the same way as they have been since their introduction. Summary: In 1995, Dr. Clark Sawin gave an address on the history of antithyroid drug development at the 11th International Thyroid Congress in Toronto, Ontario, Canada. In his review, Dr. Sawin recounted the original observations by Drs. Julia and Cosmo Mackenzie and Curt Richter at the Johns Hopkins University School of Medicine, and how their work ultimately led to Dr. Edwin (Ted) B. Astwood's seminal 1943 report on the use of thiourea and thiouracil in the Journal of the American Medical Association. He also described the development of propylthiouracil and methimazole as less toxic alternatives. He concluded his remarks by noting the often-serendipitous pathway of drug development and the role of pharmaceutical companies in the process. Conclusions: Antithyroid drugs remain a cornerstone of thyroid therapeutics. It is informative to review the process by which they came into use, as this is a seminal part of the history of thyroid disease in the 20th century. This knowledge may also spark additional research leading to new pharmacotherapies for patients with hyperthyroidism.

Expansion of the immature B lymphocyte compartment in Graves' disease.

OBJECTIVE: The specific mechanisms driving autoimmunity in Graves' disease (GD) remain largely unknown. Kappa-deleting recombination excision circles (KRECs) are circular DNA molecules generated during B cell maturation in the bone marrow which provide a measure of B cell production and proliferation. We aimed to investigate the association between KRECs and B cell subpopulations, with thyroid status and clinical outcome in GD patients. METHODS: Kappa-deleting recombination excision circles were measured by quantitative real-time PCR using a triple-insert plasmid control in 132 GD patients and 140 healthy controls. In addition, KRECs in GD patients on withdrawal of antithyroid drug (ATD) and 6-10 weeks later were analysed according to a clinical outcome at 1 year. Flow cytometry was performed on isolated CD19+ B cells to quantitate 7 B lymphocyte subpopulations in 65 GD patients. RESULTS: Circulating KRECs were higher in GD vs. controls (P = 1.5 × 10-9) and demonstrated a positive correlation to thyroid hormones and autoantibodies (free thyroxine: P = 2.14 × 10-5, rho = .30; free triiodothyronine: P = 1.99 × 10-7, rho = .37; thyroid stimulating hormone receptor autoantibodies: P = 1.36 × 10-5, rho = .23). Higher KRECs in GD patients 6-10 weeks after ATD withdrawal were associated with relapse of hyperthyroidism at 1 year (P = .04). The KRECs were positively correlated to the total CD19+ B cell count (P = 3.2 × 10-7). CONCLUSIONS: This study reports a robust association between KRECs and GD, highlighting the importance of B cells in the pathogenesis of GD and the influence of thyroid status on B cell activity. The findings indicate a potential role for KRECs as a marker of disease activity and outcome in GD.

Clinical manifestations and early effectiveness of methimazole in patients with graves' hyperthyroidism-related severe hepatic dysfunction.

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.

Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study.

BACKGRUOUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. CONCLUSION: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Thyroid function test variability and cardiovascular morbidity in hyperthyroidism.

OBJECTIVE: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8-2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses. RESULTS: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03-1.09), male gender (OR: 2.33, 95% CI: 1.03-5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01-1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14-0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00-1.05). CONCLUSIONS: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs.

Azathioprine as an adjuvant therapy in severe Graves' disease: a randomized controlled open-label clinical trial.

Introduction: Azathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves' disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness. Methods: We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40-120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission. Results: A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs. Conclusion: AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission. Trial registry: The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).

Hyperthyroidism in Danish Pregnant Women During a 20-Year Period.

CONTEXT: Hyperthyroidism in pregnancy is a clinical concern, and surveillance of any change in the occurrence of hyperthyroidism in pregnancy is important, especially when a mandatory iodine fortification (IF) program is implemented such as in Denmark in the year 2000. OBJECTIVE: To investigate any change in the occurrence of hyperthyroidism and the use of antithyroid drugs (ATDs) in Danish pregnant women during a 20-year period before and after the implementation of IF. METHODS: A nationwide register-based cohort (1997-2016) and 2 birth cohorts with biochemical data (the Danish National Birth Cohort, 1997-2003, and the North Denmark Region Pregnancy Cohort, 2011-2015) were used to study maternal use of ATDs in pregnancy and frequency of early pregnancy biochemical hyperthyroidism during a 20-year period prior to and after the implementation of mandatory IF. RESULTS: In the nationwide cohort, the adjusted odds ratio (aOR) for treatment with ATDs was 1.51 (95% CI, 1.30-1.74) after mandatory IF (2001-2004) compared with baseline (1997-1999). The increase was more pronounced in the previously moderately iodine-deficient West Denmark (aOR 1.67; 95% CI, 1.36-2.04) than the mildly deficient East Denmark (aOR 1.30; 95% CI, 1.06-1.60) and returned to baseline levels at the end of follow-up in both regions. No time-related difference in early pregnancy biochemical hyperthyroidism was observed. CONCLUSION: The use of ATDs in Danish pregnant women increased following the implementation of IF and then leveled out. Results comply with observations in the general Danish population and suggest that IF influences the occurrence of autoimmune hyperthyroidism in younger individuals.