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Objective: As thionamide is associated with various adverse effects, we re-evaluated the practical efficacy of potassium iodide (KI) therapy for Graves' hyperthyroidism (GD)., Methods: We administered KI (mainly 100 mg/day) to 324 untreated GD patients and added methimazole (MMI) only to those remaining thyrotoxic even at 200 mg/day. When the patient became hypothyroid, MMI, if taken was stopped, then levothyroxine (LT4) was added without reducing the KI dose. Radioactive iodine (RI) therapy or thyroidectomy was performed whenever required. We evaluated the early effects of KI at 2-4 weeks and followed patients for 2 years., Results: At 2 weeks, serum thyroid hormone levels decreased in all 324 patients. At 4 weeks, fT4, fT3, and both fT4 and fT3 levels became normal or low in 74.7%, 50.6%, and 50.6% of patients, respectively. In a cross-sectional survey over 2 years, GD was well-controlled with KI or KI + LT4 (KI-effective) in >50% of patients at all time points. Among 288 patients followed for 2 years, 42.7% remained 'KI-effective' throughout the 2 years (KI Group), 30.9% were well-controlled with additional MMI given for 1-24 months, and 26.4% were successfully treated with ablative therapy (mainly RI). Among 'KI-effective' patients at 4 weeks, 76.5% were classified into the KI Group. No patients experienced adverse effects from KI., Conclusion: KI therapy was useful in the treatment of GD. A sufficient dose of KI was effective in >50% of GD patients from 4 weeks to 2 years, and 42.7% (76.5% of 'KI-effective' patients at 4 weeks) remained 'KI-effective' throughout the 2 years.

The relationships between the thyroid and the heart are close and complex. In rare cases, hyperthyroidism induced by Graves' disease can be complicated by an acute myocarditis, which may be life-threatening. We report the case of a 41-year-old woman with Graves' disease not controlled by antithyroid drugs, hospitalized for odynophagia, palpitations due to atrial fibrillation, diffuse ST elevation on ECG and an increase in cardiac troponin. Coronary angiography was normal, cardiac MRI confirmed acute myocarditis. The evolution was favorable after a phase marked by supraventricular and ventricular rhythm disorders. The diagnostic and therapeutic challenge of this association are discussed, with a review of the literature., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêt., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Graves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). Although Graves hyperthyroidism is relatively common, no causal treatment options are available. Established treatment modalities are antithyroid drugs, which reduce thyroid hormone synthesis, radioactive iodine and surgery. However, emerging drugs that target the main autoantigen (monoclonal antibodies, small molecules, peptides) or block the immune pathway have been recently tested in clinical trials. Graves disease can involve the thyroid exclusively or it can be associated with extrathyroidal manifestations, among which Graves orbitopathy is the most common. The presence of Graves orbitopathy can change the management of the disease. An established treatment for moderate-to-severe Graves orbitopathy is intravenous glucocorticoids. However, recent advances in understanding the pathogenesis of Graves orbitopathy have allowed the development of new target-based therapies by blocking pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R), with several clinical trials providing promising results. This article reviews the new discoveries in the pathogenesis of Graves hyperthyroidism and Graves orbitopathy that offer several important tools in disease management., (© 2024. Springer Nature Limited.)

Context: Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves disease (GD)., Objective: To evaluate current practices in managing GD and compare them to previous surveys., Methods: We used a global online survey of endocrinologists to assess shifts in the diagnosis, monitoring, and treatment in a typical patient with GD, as well as treatment variation in 5 different clinical scenarios., Results: A total of 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of thyrotropin receptor antibody (TRAb) and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The United States had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active thyroid eye disease or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively)., Conclusion: Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Hypokalemia is a common laboratory finding in hospitalized patients, typically resulting from insufficient potassium intake, renal or gastrointestinal losses, or intracellular shifts. While the underlying cause is often easily identifiable, certain cases present diagnostic challenges, and if left unrecognized, the consequences can be life-threatening. We report a rare and atypical case of severe symptomatic hypokalemia as the initial presentation of newly diagnosed Graves' disease. The condition was caused by thyrotoxic periodic paralysis, a rare but serious complication of thyrotoxicosis, predominantly seen in East Asian populations. This disorder is characterized by episodes of acute, reversible muscle weakness associated with transient hypokalemia, which increases the risk of falls and traumatic injuries. The prompt identification of the etiology in such cases is critical for preventing recurrence and avoiding potentially fatal complications.

Graves' disease is the leading cause of autoimmune hyperthyroidism. Thyroid hormones are an essential element of the endocrine system, playing a pivotal role in the body's development, especially important in children with intensified growth. Disturbance within thyroid tissue certainly affected the whole body. Nowadays, numerous research studies indicate different factors contributing to the onset of the disease; however, the exact pathomechanism of Graves' disease is still not fully understood, especially in the context of immune-related processes. Th1, Th17, and Th22 effector lymphocytes were found to be crucial participants in the disease outcome, as well as in autoimmune diseases. Here, our study aimed at assessing selected effector T lymphocytes, Th1, Th17, and Th22, in newly diagnosed pediatric Graves' disease patients, together with their association with thyroid-related parameters and the potential outcome of disease management. We indicated significant increases in the frequencies and absolute numbers of selected effector lymphocytes in Graves' disease patients. In addition, their mutual ratios, as well as Th1/Th17, Th/Th22, and Th17/Th22, seem to be significant in those diseases. Notably, low Th17/Th22 ratio values were distinguished as potential prognostic factors for normalizing TSH levels in response to methimazole treatment. To sum up, our research determines the crucial contribution of Th1, Th17, and Th22 cells in the pathogenesis of Graves' disease. Moreover, the mentioned subset of T cells is highly likely to play a substantial role in the potential prediction of therapy outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Starosz, Stożek, Opęchowska, Bossowski, Moniuszko, Grubczak and Bossowski.)

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD. NEW & NOTEWORTHY Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24-1.60), thyroid cancer (HR: 15.51, CI: 12.29-19.57), prostate cancer (HR: 1.48, CI: 1.28-1.71), and ovarian cancer (HR: 1.31, CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66-48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

Aims: To investigate the impact of various clinical factors associated with Graves' disease on the success rate of radioiodine (RAI) therapy for Graves' disease within 3 years, and to determine the optimal range of iodine dosage per unit volume that yields the highest cure rate for Graves' disease within 1 year., Materials and Methods: This retrospective study included patients diagnosed with Graves' disease who underwent RAI therapy at the Second Affiliated Hospital of Anhui Medical University between October 2012 and October 2022. The cumulative success rate was analysed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were employed to evaluate factors associated with successful treatment of Graves' disease. Outcomes were categorized as either success or failure for all patients., Results: Overall, 1994 patients were enrolled in this study, including 594 (29.8%) male and 1399 (70.2%) female patients. The success and failure groups comprised 1645 (82.4%) and 349 patients (17.6%), respectively, after a 3-year follow-up period. Multivariate regression analysis demonstrated that sex, antithyroid drug (ATD) use before RAI therapy, age, thyroid receptor antibody (TRAb) levels, iodine dose, thyroid mass, and early ATD use before RAI therapy were independent influencing factors for Graves' disease cure., Conclusions: We found that female patients and those with TRAbs ≥31.83 IU/L and thyroid mass ≥ 73.42 g had a lower cure rate. Therefore, thyroid size, disease severity, and duration of disease should be comprehensively considered when making treatment decisions and iodine dose selection in clinical practice., (© 2024 John Wiley & Sons Ltd.)

The aim was to compare the lipid profile of patients with GD treated with anti-thyroid drugs (ATDs) using a titration regimen versus a block and replace regimen. This is an 18-month prospective observational study. In this study were included 149 medically treated GD patients, aged+>+18 years. Pregnant women and patients treated with radioactive iodine therapy or partial/total thyroidectomy were excluded. Patients were divided into 2 subgroups: titration (A) and block and replace (B) therapy, according to the ATD regimen used. Thyroid and metabolic profile was measured at baseline and at least one visit during medical treatment. The whole group included 122 (81.87%) females (F) and 27 (18.12%) males (M), ratio F:M=4.5:1. As expected, at the time of diagnosis, thyrotoxic patients were with normal lipid profile. During medical treatment, in patients who achieved euthyroidism, the cholesterol levels increased as follows: in subgroup A: by 52.9 mg/dl (95% CI: 26.4-79.3), p<0.001 for total cholesterol (T-C), by 33.3 mg/dl (95% CI: 10.3-56.3), p=0.007 for low-density lipoprotein cholesterol (LDL-C) and by 11.44 mg/dl (95% CI: 3.08-19.79), p=0.009 for high-density lipoprotein cholesterol (HDL-C); in subgroup B T-C increased by 45.1 mg/dl (95% CI: 22.2-68), p<0.001 and for LDL-C by 33.57 mg/dl (95% CI: 12.72-54.42), p=0.003. No statistically significant increase in triglyceride levels was determined. Medical treatment of hyperthyroidism due to Graves' disease increased cholesterol levels regardless of the ATD regimen used., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Graves' disease (GD) is an auto-immune cause of hyperthyroidism. First-line treatment often consists of a 12-18 month course of antithyroid drugs (ATD). After discontinuation of ATD, GD relapses in approximately 50% of patients. The 'Graves recurrent event after therapy+ ' (GREAT+) score may predict individual relapse chances after ATD discontinuation more accurately based on clinical and laboratory parameters at diagnosis. We investigated the need for the GREAT+ score through an online questionnaire among GD patients and physicians treating GD., Methods: An anonymous online questionnaire was distributed to patients and physicians between June 2022 and August 2023., Results: The questionnaire was completed by 532 patients and 44 physicians. Results showed that 94% of patients were interested in knowing their GREAT+ score at the start of treatment. 55% would consider definite treatment (radioiodine/thyroidectomy) as first-line treatment in case of a high relapse chance. 98% of the physicians indicated the GREAT + score would support patient counseling. 84% may change their advice for first-line treatment if a patient has a high relapse chance based on the score., Conclusion: Patients and physicians considered the GREAT+ score as a valuable addition to the current available information which could change treatment decisions. Therefore, external validation of the GREAT+ score is justified to implement this score in clinical practice., (© 2024. The Author(s).)

Purpose: Abnormal liver blood tests (ALBTs), neutropenia (NEU) and thymic hyperplasia (TH) are new features of Graves' disease (GD). Our objectives were: (a) to calculate the accuracy of TH in discriminating between Graves' and non-Graves' thyrotoxicosis, compared to ALBTs, NEU and Graves' orbitopathy (GO); (b) to explore the outcome of GD-associated TH and non-GD-associated TH., Methods: We prospectively analyzed consecutive adult patients with newly diagnosed thyrotoxicosis from January 2018 to June 2023. TH was detected via neck ultrasound (nUS) then confirmed and followed by magnetic resonance imaging (MRI). For GD vs non-GD clinical sensitivity (SE) and specificity (SPEC), accuracy, positive predictive value (PPV) and negative predictive value (NPV) of GO, TH, ALBTs and NEU were calculated., Results: 264 thyrotoxic patients were included. TH was found in 16.4% (20/122) of GD vs 1.4% (2/142) in non-GD (p < 0.001). SE, SPEC, accuracy, PPV and NPV of the four extrathyroidal manifestations of GD were as follows, respectively: GO 26%, 100%, 66%, 100%, 61%; ALBTs 41%, 89%, 69%, 76%, 66%; NEU 5%, 100%, 56%, 100%, 55%; TH 16%, 98%, 61%, 91%, 98%. In 18 of them, TH regressed within 12 months after achieving euthyroidism under anti-thyroid drug therapy, while in the remaining 2, TH regressed 6 months after thyroid surgery. In the two non-GD patients with TH, thymus disappeared along with euthyroidism., Conclusions: TH in the hyperthyroidism scenario provides a high PPV for GD. A conservative approach for the diagnostic work-up and initial management of thyrotoxicosis-associated TH should be adopted., (© 2024. The Author(s).)

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD)., Objective: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4 + , CD8 + , CD25 + and CD20 + . We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood., Methods: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4 + , CD8 + , CD25 + and CD20 + markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4 + (helper T lymphocytes), CD8 + (cytotoxic T lymphocytes), CD25 + (regulatory T lymphocytes) and CD20 + (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed., Results: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20 + expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate., Conclusion: We found a lower proportion of intrathyroidal CD20 + B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Denise Engelbrecht Zantut Wittmann reports equipment, drugs, or supplies and statistical analysis were provided by State University of Campinas. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The most common cause of hyperthyroidism, Graves' disease is a common organ-specific autoimmune disease. Selenium is an essential trace element of the human body that is mainly concentrated in the thyroid gland and is involved in the synthesis and metabolism of thyroid hormones. Most studies have shown that the level of selenium is closely related to the occurrence and development of thyroid diseases, and selenium supplementation can help improve thyroid function. This study aims to evaluate the efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment., Methods and Analysis: We will search the electronic databases including PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data and Chinese Biomedical Literature, and the time was deadline to December 2023. To evaluate the efficacy of methimazole combined with selenium supplementation in the treatment of Graves' hyperthyroidism, randomised controlled trials will be included. The Cochrane Collaboration's risk of bias tool will be used to assess the quality of all included studies, and the baseline data of all the studies are extracted by the authors. A random-effects model or a fixed-effects model is used to analyse the outcomes. The primary outcomes are the levels of selenium, triiodothyronine, free thyroxine and thyroid-stimulating hormone (TSH), whereas the secondary outcomes include TSH receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody., Ethics and Dissemination: Ethics approval is not required since no original data will be collected. The results of this study will be published in a peer-reviewed journal., Prospero Registration Number: CRD42023410999., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use., Method: We conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study., Results: The study sample consisted of 189 patients, 72% of whom were female. The patients' median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001., Conclusion: The remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD., (© 2024. The Author(s).)

Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves’ disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts (CBC) monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of CBC may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

To investigate liver function changes, blood glucose fluctuation, insulin secretion and gender differences in hyperthyroidism patients before and after propranolol with methimazole. Clinical data 110 hyperthyroidism patients admitted to Zhangzhou Affiliated Hospital of Fujian Medical University from February 2023 to February 2024 were retrospectively analyzed. They were categorized into the methimazole group (methimazole, n = 55) and the coalition medication group (Methimazole with propranolol, n = 55). The therapeutic effects of both groups were observed. Pre- and post-treatment liver function dynamic blood glucose parameters and insulin secretion characteristics were analyzed between the two groups. Gender differences prior to treatment were also examined. Overall efficacy was significantly higher in the oalition group (96.35%) than in the methimazole group (83.64%) (P<0.05); Post-treatment, the TBiL, AST, ALT, FT 3 , FT 4 , FBG, P1BG, HOMA-IR, HOMA-β, postprandial blood glucose peak value, LAGE, MAGE, MODD and SDBG levels in the coalition group were lower compared to the methimazole group, while TSH was higher (P<0.05). Female patients exhibited significantly lower LAGE, MAGE, MODD and SDBG levels compared to the male group (P<0.05). The combination of methimazole and propranolol enhances thyroid and liver functions for hyperthyroid patients while improving insulin resistance along with reducing postprandial blood glucose variability.

We describe the clinical presentation and evaluation of a 10-year-old boy who presented to our medical center with years of progressive proximal muscle weakness, muscle atrophy, and weight loss. In addition to a myopathic phenotype, he was found to have tachycardia, tremor, and learning difficulties. Electromyography revealed chronic myopathic changes and laboratory screening was notable for undetectable thyroid stimulating hormone. Follow-up testing revealed elevated thyroid peroxidase antibodies and thyroid stimulating immunoglobulins. Ultrasound examination revealed an enlarged heterogeneous thyroid gland. Four weeks after treatment with atenolol and methimazole, his strength and cognition began to improve. This case highlights the importance of evaluating for potentially reversible toxic-metabolic etiologies in children presenting with any progressive neurologic symptoms., (Copyright © 2024 by the American Academy of Pediatrics.)

This review summarizes the diagnosis and management of thyrotoxicosis in pregnancy. The diagnostic clinical and biochemical considerations used to distinguish the various etiologies of hyperthyroidism from appropriate physiologic changes during pregnancy will be outlined. Finally, the review will discuss the risks and benefits of available options for the treatment of thyrotoxicosis during pregnancy, to mitigate the risks of fetal hyperthyroidism., Competing Interests: Disclosures The authors have nothing to disclose., (Published by Elsevier Inc.)

Objective: The objective of this study is to clarify the clinical features of thyroid dysfunction observed in patients with autoimmune pancreatitis (AIP)., Methods: We repeatedly examined thyroid function in 74 patients with type 1 AIP (58 males, 16 females; average onset age of AIP 67 years). Clinical and serological findings in patients with thyroid dysfunction were analyzed., Results: During follow-up, clinical and subclinical hypothyroidism were observed in 3 and 17 patients, respectively. Clinical and subclinical hyperthyroidism were observed in 5 and 1 patients, respectively. One patient showed clinical hyperthyroidism followed by subclinical hypothyroidism. All patients with clinical and subclinical hypothyroidism were asymptomatic and required no medical treatment, whereas four patients with clinical hyperthyroidism were symptomatic and received treatment with thiamazole., Conclusion: Frequent hypothyroidism in AIP, which was previously reported, was confirmed. Moreover, in this study, the association between hyperthyroidism and AIP was demonstrated. Hyperthyroidism in AIP may be more clinically significant than hypothyroidism because patients frequently require medical treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Acute viral myocarditis and hyperthyroidism can present with acute coronary syndrome. However, the link between hyperthyroidism and myocarditis has hardly been explored apart from a small collection of published case reports. We report a case where a patient presents with severe chest pain and was found to have concomitant severe coronary vasospasm and acute myocarditis and was diagnosed with Graves' disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Treatment patterns and preferences for patients with Graves' disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Backgruound: Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves' hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established., Methods: In this retrospective cohort study, 1,235 patients with Graves' hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12-24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared., Results: The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1., Conclusion: The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves' hyperthyroidism who underwent longer ATD treatment duration.

Objectives: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drugs (ATDs) are the first-line treatment, but when discontinued, >50% of patients experience relapses. Conventional definitive treatment options include surgery and radioiodine therapy (RAI), each with its own disadvantages. Radiofrequency ablation (RFA) achieved promising short-term remission rates in a previous pilot study. The current study reports our experience of using RFA to treat relapsed GD in the largest cohort of patients with a longer follow-up period. Methods: This single-arm prospective study recruited consecutive patients aged ≥18 with persistent/relapsed GD requiring ATD from two tertiary endocrine surgery centers. Those with compressive goiter, suspected thyroid malignancy, moderate-to-severe Graves' ophthalmopathy, preference for surgery/RAI, or pregnancy were excluded. Eligible patients received ultrasound-guided RFA to the entire bulk of the thyroid gland. ATDs were discontinued afterward, and thyroid function tests were monitored bimonthly. The primary outcome was the disease remission rate at 24 months follow-up after single-session RFA, defined as being biochemically euthyroid or hypothyroid without ATD. Secondary outcomes were complication rates. Results: Of the 100 patients considered, 30 (30.0%) patients were eligible and received RFA. Most were female patients (93.3%). The median total thyroid volume was 23 mL (15.9-34.5). All completed 24 months follow-up. After single-session RFA, disease remission rates were 60.0% at 12 months and 56.7% at 24 months. Among the 13 patients with relapse after RFA, 9 (69%) required a lower ATD dose than before RFA; 2 received surgery without complications. Total thyroid volume was the only significant factor associated with relapse after RFA (odds ratio 1.054, confidence interval 1.012-1.099, p = 0.012). At 24 months, RFA led to disease remission in 100% of the 9 patients with a total thyroid volume <20 mL and 35% of patients with a total thyroid volume ≥20 mL ( p = 0.007). There was no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. Conclusions: In a highly selected group of patients with relapsed GD and predominantly small thyroid glands, single-session RFA may achieve disease remission. Smaller total thyroid volume may be a favorable factor associated with disease remission after RFA. The results of this study need to be confirmed with a long-term clinical trial. Clinical Trial Registration: This study is registered at www.clinicaltrial.gov with identifier NCT06418919.

Background: Pseudo-orthostatic tremor is a hyperkinetic movement disorder usually associated with other neurological comorbidities, mainly Parkinson's disease., Case Report: A 65-year-old male presented with unsteadiness and leg tremor while standing. Electrophysiological evaluation confirmed the presence of pseudo-orthostatic tremor. Blood test showed an undiagnosed Graves' disease. A complete remission of tremor was achieved with methimazole. Dopamine transporter scintigraphy showed a mild reduction of the striatal binding, bilaterally., Discussion: Graves' disease can be associated with pseudo-orthostatic tremor. Thyroid function should be assessed in patients complaining of unsteadiness. The causative role of hyperthyroidism in determining dopaminergic degeneration and uncovering subclinical parkinsonism warrants further investigations., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Objective: We identified the associated factors and compared the survival times of feline hyperthyroidism (FHT) between thyroidectomy and methimazole alone., Methods: The medical records of 41 cats diagnosed with new-onset hyperthyroidism were retrospectively reviewed. The cats were categorized into the thyroidectomy (n = 15) and methimazole (26) treatment groups. Survival analyses using the Kaplan-Meier method, log-rank test, and Cox proportional hazards models were conducted to compare the time to the selected outcomes., Results: Univariate analysis revealed that survival time was significantly longer with thyroidectomy than with methimazole (P < .001). Multivariate analyses revealed thyroidectomy as an independent prognostic factor for good outcomes (hazard ratio, 0.209; 95% CI, 0.073 to 0.601; P = .004). The recurrence rate was significantly lower in cats that underwent thyroidectomy than in those that received methimazole alone (P = .011)., Clinical Relevance: Compared with methimazole alone, thyroidectomy was associated with a longer survival time in FHT and can be considered an irreversible treatment modality in settings where radioisotopes are not available.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease characterized by the inflammation and destruction of small blood vessels and circulating ANCAs. Drugs such as antithyroid drugs (ATDs), especially propylthiouracil (PTU), have been used for the production of ANCAs and cause the development of drug-induced AAV. The pathogenesis of this disease is unclear but could be related to the physiological processes affecting the degradation of neutrophil extracellular traps (NETs). At present, PTU is widely used in patients with Graves' disease (GD) who are preparing for pregnancy and whose condition has not been controlled. Once drug-induced AAV has occurred with important organ damage, considering NETs have a significant role in the immune system, whether the cessation of drugs could stop the progression of organ damage is unclear, and a consensus regarding standard treatment has not been established., Patient Concerns: In this case report, a female patient who planned pregnancy was hospitalized with multiple joint pain, impaired renal function, and hematuria. Immunofluorescence of the renal biopsy demonstrated spherical and diffuse mesangial distribution of IgA (3+). Autoimmune serology demonstrated positivity for autoantibodies against p-ANCA and an anti-MPO titer 74.72 RU/mL., Diagnosis: She was diagnosed with PTU-induced p-ANCA-associated and IgA-associated vasculitis (IgAV)., Interventions: The patient accepted low doses of glucocorticoid, immunosuppressive therapy and RAI treatment., Outcomes: Both her kidney function and thyroid function remained were on the mend., Conclusion: The authors believe that this type of patient needs to fully consider their pregnancy preparation needs, suspend pregnancy when a small chance of GD remission is indicated, and avoid the use of drugs with reproductive toxicity and other serious adverse events. The multidisciplinary combination therapy of low-dose glucocorticoids and immunosuppressants combined with iodine radiotherapy is one reasonable scheme. At the same time, it is necessary to eliminate the organ damage caused by other reasons. This report provides a clinical treatment basis for patients with drug-induced vasculitis manifestations who cannot receive an accurate diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Perchlorates are ionic inhibitors antagonizing iodine transport into thyrocytes, hampering thyroid hormone synthesis. Nevertheless, perchlorates are not considered as first-line treatment in hyperthyroidism and thyrotoxicosis as compared to other pharmacological and non-pharmacological interventions., Aim: Reassessing the therapeutic role of perchlorates in hyperthyroidism and thyrotoxicosis throughout a systematic review of the Literature., Methods: Guidelines were searched and examined to summarize current recommendations on the use of perchlorates in the management of hyperthyroidism. Randomized and non-randomized clinical trials were also searched and reviewed to summarize the efficacy/effectiveness and safety of perchlorates in hyperthyroidisms and thyrotoxicosis., Results: The management of specific forms of hyperthyroidism was considered, including Graves' disease (GD) in non-pregnant adults, hyperthyroidisms in pregnancy, iodine media contrast-induced hyperthyroidism, amiodarone-induced hyperthyroidisms, and thyroid storm. Most of the reported studies had remarkable limitations in terms of study design (non-controlled trials, lack of blinding), low number of participants, and the lack of clinically relevant endpoints, such as cardiovascular events, cardiovascular mortality, and teratogenicity. Overall, perchlorates could be considered a second-line treatment after thionamides, radioiodine, and total thyroidectomy in both GD and hyperthyroidisms in pregnancy. The therapeutic potential of perchlorates alone or in combination with other agents could be considered a second-line treatment of iodine-related hyperthyroidisms and thyroid storm., Conclusion: Despite the low level of evidence, perchlorates could be considered in such specific forms of thyroid disorders, including iodine-induced hyperthyroidism and thyroid storm., (© 2024. The Author(s).)

Objective: Subacute thyroiditis is also known as subacute granulomatous thyroiditis, giant cell thyroiditis, painful thyroiditis, and De Quervain's thyroiditis. Immature granulocytes (IG) and neutrophil-to-lymphocyte ratio (NLR) are new inflammatory markers that are easily detected in routine complete blood count (CBC) tests. The aim of this study was to investigate the role of IG and NLR as markers of treatment response in patients with subacute thyroiditis., Subjects and Methods: The study included 41 patients with subacute thyroiditis treated and monitored in our outpatient clinic between April 2020 and April 2022. From a retrospective review of medical records, we recorded results of IG, NLR, thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) from blood tests obtained routinely before and after treatment., Results: Overall, 31 (75.6%) patients were women and 10 (21.4%) were men. The median age was 41 years (range 22-68 years). The laboratory tests showed the following median (range) results: IG, 0.03 (0.01-0.08); NLR, 3.6 (1.2-5.2); TSH, 0.02 mIU/L (0.01-3.35 mIU/L); fT4, 2.3 ng/dL (1.0-7.0 ng/dL); fT3, 5.6 pmol/L (2.6-15.2 pmol/L); ESR, 49 mm/h (17.0-87 mm/h); and CRP, 73 mg/dL (3.0-188 mg/dL)., Conclusion: Early diagnosis and treatment of subacute thyroiditis is fundamental. In the present study, the new inflammatory markers IG and NLR, measured routinely on CBC tests, decreased significantly after subacute thyroiditis treatment relative to pretreatment values. After treatment, the NLR change correlated with ESR and CRP changes, while the IG change correlated only with CRP change. These findings suggest that the markers IG and NLR may be used to evaluate treatment response in patients with subacute thyroiditis., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

A 49-year-old Japanese woman was admitted to our hospital with weight loss of 15 kg, nephrotic-range proteinuria (4.5 g/g.Cre), and hematuria over a 6-month period. She had received two doses of the coronavirus disease 2019 (COVID-19) vaccine one year before the onset of the disease, after which the estimated glomerular filtration rate increased. Laboratory tests and other tests led to a diagnosis of hyperthyroidism, and a kidney biopsy showed thrombotic microangiopathy-like glomerular microangiopathy comprising mainly glomerular endothelial cell damage. Thiamazole (30 mg) was started for the hyperthyroidism. Three months later, the thyroid function normalized, and two months later, the proteinuria and hematuria disappeared, suggesting that COVID-19 vaccination and these events were related.

Hyperthyroidism is increased synthesis and secretion of thyroid hormones by the thyroid gland resulting in thyrotoxicosis. The modality of therapy for hyperthyroidism includes anti-thyroid drugs, radioiodine and surgery. Anti-thyroid drugs are the only available therapy for hyperthyroid patients in developing world as radioiodine is inaccessible and surgical set up does not exist as required. The aim of this study was to determine the magnitude and predictors of uncontrolled hyperthyroidism among hyperthyroid patients after prolonged anti-thyroid drug use. An institutional-based cross sectional study was conducted at the University of Gondar hospital, Northwest Ethiopia, between April 1, 2022 and October 31, 2022. A consecutive sampling method was used to recruit 317 study subjects. Data were collected through a pre-designed questionnaire. Patients were interviewed to obtain socio-demographic data and relevant medical information. Laboratory analyses were done based on the follow up protocol. Data were entered into EPI Info version 4.6.0.0 (EPI Info, Atlanta) and analyzed in STATA version 14 (Stata Corp LP, Texas, USA). Binary logistic regression model was used to identify variables associated with uncontrolled hyperthyroidism among hyperthyroid patients. P value < .05 was used to declare significant association. A total of 317 patients with hyperthyroidism were included in the study. The median age of the study subjects was 45 years (IQR 36-55 years). Most (95%) of the study participants were females. Toxic multi-nodular goiter was the most common cause of hyperthyroidism (92%), followed by toxic adenoma (5%) and Graves' disease (2%). On multivariate binary logistic regression, large goiter size (AOR: 3.163, 95% CI [1.333-7.506]), severe disease (AOR: 2.275, 95% CI [1.060-4.880]), infrequent iodinated salt intake (AOR: 3.668, 95% CI [1.245-10.802]), and poor adherence to anti-thyroid drug (AOR:15.724, 95% CI [5.542-44.610]) were statistically significant with uncontrolled hyperthyroidism at 12 months of anti-thyroid drug intake. A quarter of patients with hyperthyroidism didn't achieve euthyroid state after 12 months of anti-thyroid drug use. The identified predictors for non-euthyroid state were large goiter size, severe disease, infrequent iodinated salt intake, and poor adherence to anti-thyroid drug., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19., Methods: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase., Results: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses., Conclusion: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function., Competing Interests: Disclosure F.T.T.L has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council. X.L has received research grants from the Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. E.Y.F.W has received research grants from the Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. C.S.L.C has received grants from the Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. E.W.Y.C reports honorarium from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. C.K.H.W reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund; AstraZeneca and Boehringer Ingelheim, unrelated to this work. I.C.K.W reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years. All other authors declare no competing interests., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. Methods: We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Results: Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; p = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; p = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10-1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger ( p = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; n = 20/40) than in those receiving MMI (16.5%; n = 18/110; p = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); p = 0.004. Conclusions: Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD.

While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jeong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

Purpose: In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism., Methods: A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment., Results: Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight., Conclusion: A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Thyrotoxic periodic paralysis is a rare and serious complication of hyperthyroidism., Case Presentation: A man in his thirties of Asian descent, with non-compliant Graves' disease, presented with extremity paresis. Emergency blood tests revealed severe hypokalaemia, leading to a diagnosis of thyrotoxic periodic paralysis. The combination of uncontrolled hyperthyroidism, Asian ethnicity, paralysis, and severe hypokalaemia without other causes defined the diagnosis. Acute treatment involves non-selective beta-blockers, addressing hyperthyroidism, and potassium supplements., Interpretation: Swift recognition of thyrotoxic periodic paralysis is crucial for timely and life-saving treatment. If triggered by hyperthyroidism, as in Graves' disease, surgery or radioiodine is strongly indicated for definitive treatment. It is noteworthy that euthyroid patients cannot develop thyrotoxic periodic paralysis.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively., Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT 3 and FT 4 before and after treatment (FT 3 -P/FT 3 -A, FT 4 -P/FT 4 -A) on whether BTMs recovered., Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT 3 -P/FT 3 -A and FT 4 -P/FT 4 -A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05)., Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT 3 decreased more than 51% and FT 4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Chai, Zheng, Jia, Tan, He, Zhang, Men, Liu, Shi, Ren, Dong, Liu and Meng.)

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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 (LT 4 ). Even when LT 4 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 LT 4 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 LT 4 treatment. He developed hyperthyroidism and moderate-severe GO. Despite stopping LT 4 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., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism., Methods: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO)., Results: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment., Conclusions: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO., (© 2024 The Authors. World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: The aim of this study was to find predictive factors for intractable Graves' disease (GD)., Methods: Ninety-three GD patients who visited two pediatric endocrinology clinics from March 2009 to August 2019 were involved in this study. Data were collected on the methimazole (MZ) dosages prescribed from their first visits to their fifth visits. The amount of tapered dosage was presented as a "tapering velocity" (dosage difference (mg/m 2 )/follow-up interval (months)). The relationship between the tapering velocity and the remission rate of GD was analyzed. Remission of GD was defined as having a total period of MZ treatment less than 5 years with no relapse after MZ withdrawal for at least more than a year., Results: Of 93 patients diagnosed with GD, 26 patients (28.0%) were classified as the "remission group" and 67 (72.0%) were classified as the "intractable group." The frequency of goiter was significantly higher in the intractable group (p = 0.031). Multivariate logistic analysis revealed that the tapering velocity change from the first to the fifth visit significantly influenced the risk of intractable GD: odds ratio (OR) = 0.598, 95% confidence interval (CI) 0.413-0.865, p = 0.006. An accompanying goiter at the time of diagnosis (OR = 4.706 95% CI 1.315-16.847, p = 0.017) and thyroid stimulation hormone receptor antibody titer (OR = 1.032 95% CI 1.002-1.062, p = 0.034) were also found to be independent factors associated with intractable progress in GD., Conclusion: Difficulty in tapering the MZ dosage in the first 4 months of treatment was an independent predicting factor for intractable GD., (© 2024 Japan Pediatric Society.)

Introduction: Drug therapy for Graves' disease (GD) is the first-line treatment in Europe. The use of a specific regimen for the administration of anti-thyroid drugs (ATDs) is still controversial. The objective was to compare block-and-replace therapy (BRT) with a titration (T) regimen in terms of incidence of overt hypothyroidism and development of Graves' orbitopathy (GO) over 18 months of treatment., Material and Methods: Two databases (PubMed, Cochrane Library) and reference lists were searched. Prospective and retrospective observational cohort studies were included. Data collection and analysis were performed independently by 2 authors., Results: Two studies with 716 GD patients (40.36% treated with BRT, 59.64% with T regimen) were included. No statistically significant differences were observed between the ATDs regimens used in terms of incidence of overt hypothyroidism during 18 months of treatment [Mantel-Haenszel (M-H) odds ratio (OR): 1.54, 95% confidence interval (CI): 0.75-3.16, p-value = 0.24]. GD patients who followed BRT were less likely to achieve control of thyroid function than patients on T regimen (M-H OR: 0.55, 95% CI: 0.34-0.88, p = 0.01). One study reported fewer thyroid function tests (TFT) during BRT than during the T regimen. The other study included patients without GO at baseline and reported a lower incidence of GO during BRT than in the T regimen (9.1% versus 17.8%), with no statistical difference between the 2 regimens (M-H OR: 0.47, 95% CI: 0.19-1.14, p = 0.10)., Conclusion: BRT may be more useful than the T regimen for patients with complicated GD or for those who required fewer TFTs.

We present a case report on a spot diagnosis of Thyrotoxic Periodic Paralysis (TPP) with a unique first-person account of events from the patient. It illustrates the importance of pattern recognition and exemplifies how timely treatment enables quick resolution of a life-threatening medical emergency. Patient X's account affirms the condition's insidious onset and rapid deterioration. This case highlights the need for raising awareness of diseases that are more prevalent in specific ethnic groups and is particularly crucial for work in culturally diverse environments. We hope by sharing our experience, readers will be prompted to consider TPP as a differential diagnosis for acute limb weakness in an acute setting; with prompt testing of thyroid function and initiation of the appropriate treatments.

Thyrotoxic periodic paralysis (TPP) and thyrotoxic cardiomyopathy (TCMP) are potentially lethal complications of thyrotoxicosis that require emergent recognition and management to attenuate significant morbidity and mortality. We present the case of a 23-year-old Asian male with no prior medical history who developed TPP with coincident TCMP, which was successfully managed with antithyroid and heart failure therapies. The clinician should be aware of the diagnosis and treatment of these 2 life-threatening conditions in a hyperthyroid state., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.