Unilateral gynecomastia as an initial presentation of hyperthyroid Graves’ disease

Summary Graves’ disease is an autoimmune condition leading to the activation of and an increase in thyroid hormone secretion. Manifestations of hyperthyroidism in Graves’ disease can vary among people. In this case, we report a 24-year-old Thai man with a rare presentation of unilateral gynecomastia along with symptoms of thyrotoxicosis. Physical examination revealed a 3 cm non-tender palpable glandular tissue beneath and around the left areola without nipple discharge and moderately diffuse thyroid enlargement with thyroid bruit. Thyroid function test showed a typical thyrotoxicosis state with elevated serum-free T4 and decreased serum TSH. His diagnosis of Graves’ disease was confirmed biochemically with a highly elevated anti-TSH receptor antibody. Early treatment with anti-thyroid medication was given first, followed by Radioiodine treatment (RAI) for definitive treatment due to high level of anti-TSH receptor antibody, enlarged thyroid and severe thyrotoxicosis presentation at a young age, which might not resolve by anti-thyroid medication alone. The patient responded well to treatment and achieved complete resolution of unilateral gynecomastia with clinically and biochemically euthyroid within 3 months after treatment. No recurrent gynecomastia was found during the 2-year follow-up. Learning points Characteristic of gynecomastia in hyperthyroidism is usually presented with bilateral progressive gynecomastia; however, unilateral gynecomastia is occasionally found as a presentation of hyperthyroidism. Complete resolution of gynecomastia without recurrence can be achieved within a few months of treatment after thyrotoxicosis is resolved in patients with hyperthyroidism with the recent development of gynecomastia. RAI for definitive treatment is recommended in young adult patients expressing very high anti-TSH antibody level with severe thyrotoxicosis.

Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves’ Disease Complicated with Vitamin D Deficiency

<b><i>Background:</i></b> Intestinal flora is associated with Graves’ disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. <b><i>Methods:</i></b> Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. <b><i>Results:</i></b> Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. <b><i>Conclusions:</i></b> The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.

Clinical Features and Remission Rate of Pediatric Graves’ Hyperthyroidism Treated With Antithyroid Drug

Introduction: Pediatric Graves’ hyperthyroidism needs long-term therapy and there is no specific guideline. Antithyroid medication is used as the first line of treatment, among antithyroid medication, radioiodine therapy, and surgery. The study was designed to investigate the clinical features and remission rate and the factors associated with the remission of Graves’ hyperthyroidism treated with antithyroid drug in children and adolescents. Methods: Initially, 114 children and adolescents who have been managed with thyrotoxicosis in a single tertiary center were included in the study. Retrospective review of medical records was performed on the demographic data, clinical information, and laboratory results. Ten patients with Hashitoxicosis, 36 patients who were followed less than 1 year, and 19 patients with no available initial results of thyroid function test were excluded from the study. We analyzed the clinical features and remission rate between the group with remission and the group without remission. Chi-square, Fisher’s exact test, and t-test were used for statistics. Results: A total of 49 patients were included in the study (M:F 11:38). Mean age at diagnosis was 12.6±3.7 years old and the follow up duration was 4.9±2.5 years. Goiter was visible in 47 patients (96%) and exophthalmos was found in 12 patients (24%). Thirteen patients (27%) showed treatment-related hypothyroidism during follow up. Twenty-seven patients (55%) could discontinue the medication for more than 1 month. Among those, eleven patients showed recurrence and 6 out of 11 patients reached remission again. As a result, 22 patients (45%, male 7) maintained the remission state. Average time till remission was 4.2±2.4 years. Remission rate was 2%, 8%, 12%, 35%, and 45% during the treatment of 1, 2, 3, 4, and 5 years, respectively. Mean follow up duration was significantly longer in the group with remission (5.7±2.2 years), compared with the group without remission (4.3±2.6 years) (p&lt;0.05). There was no significant difference in the presence of goiter or exophthalmos between two groups (goiter 95.5% vs 96.3%; exophthalmos 18% vs. 30%). Incidence rate of hypothyroidism during treatment was also not statistically different between the groups (36% vs. 19%). Age at onset, recent age, initial levels of T3, free T4 or TSH, and the presence of anti-thyroglobulin antibody or anti-thyroid peroxidase antibody were not significantly different between the groups. In contrast, initial levels of TSH receptor antibody was significantly lower in the group with remission (15.6±9.7 IU/L vs. 26.2±14.7 IU/L, p=0.004). Conclusion: This study showed that the remission rate was 45% during the treatment duration of 5 years. Initial titer of TSH receptor antibody was the most important factor associated with the remission in the pediatric Graves’ hyperthyroidism.

Clinical course of euthyroid subjects with positive TSH receptor antibody: how often does Graves’ disease develop?

Background Thyroid stimulating hormone (TSH) receptor antibody (TRAb) is detected in the serum of patients with Graves’ disease (GD). This study aims to investigate the prevalence of euthyroid individuals showing positive results for TRAb and to clarify the clinical course of thyroid function and TRAb levels in these subjects. Objective Subjects were female patients who newly visited our hospital for a screening test prior to fertility treatment and showed normal thyroid function and volume without nodules between 2014 and 2017. After excluding subjects with a history of thyroid disease, 5,622 subjects were analyzed. Results Forty-seven of the 5,622 subjects showed positive results for TRAb (reference range, &lt; 2.0 IU/L) at the initial visit. Median initial TRAb was 2.9 IU/L (range, 2.0 -14.7 IU/L) and median follow-up was 18.3 months (range, 0- 66.5 months). Six of the 47 subjects (12.8%) developed GD and median duration until development was 6.6 months (range, 1.2 -13.2 months). Median TRAb values initially and at diagnosisof GD for those 6 patients were 3.7 IU/L (range, 2.7 -5.1 IU/L) and 7.2 IU/L (range 3.6 -21.4 IU/L), respectively. TRAb results turned negative for 20 of the 47 subjects, but remained positive despite normal thyroid function in 13 of the 47 subjects. Conclusion GD developed over time in 12.8% of euthyroid young female patients showing positive TRAb within a median of 6.6 months. A positive result for TRAb itself did not mean development of GD, so other factors must be essential for the pathogenesis of GD.

Control of Graves’ hyperthyroidism with very long-term methimazole treatment: A clinical trial

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

Amiodarone-induced type 2 thyrotoxicosis

The authors present a case of a 55-year-old gentleman with a medical history of atrial fibrillation on amiodarone who presented with weight loss, palpitations and exertional dyspnoea. Thyroid function tests revealed thyrotoxicosis with a free thyroxine (T4) of 117 pmol/L and a thyroid-stimulating hormone (TSH) of <0.008 mIU/L. Interleukin-6 level was low. The negative TSH-receptor antibody status, the presence of a small thyroid gland with heterogeneous echotexture and decreased internal vascularity on ultrasound together with the relatively quick drop in free T4 and free tri-iodothyronine (T3) levels once prednisolone therapy was added to carbimazole suggested that this was typical of amiodarone-induced thyrotoxicosis (AIT) type 2. Subsequently, carbimazole was discontinued and treatment with prednisolone was continued. This case highlights that AIT management may be challenging and it is of paramount importance to establish the type of AIT present as this will guide management and is key to improving prognosis.

Control of Graves’ hyperthyroidism with very long-term methimazole treatment: A clinical trial

Background: Long-term antithyroid drugs therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.Methods: Fifty nine patients with Graves’ disease on long-term MMI for 14.2±2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.Results: Of 27 patients who continued MMI, 16 and 11 subjects completed median of 20 and 24 years of MMI treatment, respectively. Suppressed serum thyrotropin (TSH) was not observed in any patient after seventh years of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8±1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.Conclusions: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.Trial registration: IRCT201009224794N, 2010-10-25. Retrospectively registered.www. IRCT.IR/Trial/5143.

Control of Graves’ Hyperthyroidism with Very Long-Term Methimazole Treatment: A Clinical Trial

Background: Long-term antithyroid drugs therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.Methods: Fifty nine patients with Graves’ disease on long-term MMI for 14.2±2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.Results: Of 27 patients who continued MMI, 16 and 11 subjects completed median of 20 and 24 years of MMI treatment, respectively. Suppressed serum thyrotropin (TSH) was not observed in any patient after seventh years of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8±1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.Conclusions: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse.Trial registration: IRCT201009224794N, 2010-10-25. Retrospectively registered.www. IRCT.IR/Trial/5143.