Long-term methimazole therapy in Graves' hyperthyroidism and adverse reactions: a Danish multicenter study

PURPOSE: In this prospective multicenter study with patients newly diagnosed with Graves’ hyperthyroidism (GH), we studied the timing and characteristics of adverse drug reactions in patients treated with anti-thyroid drugs (ATD) for up to 48 months. METHODS: Patients with GH were treated with ATD until remission and hereafter with a low-dose regime to keep the patients in remission. The patients were followed with blood samples and recording of adverse events approximately every second month for the first 2 years and every third month for the following 2 years. RESULTS: We included 208 patients and the patients were treated for a median of 22 (range: 0.5–49) months. Ten percent of the patients experienced adverse drug reactions and 75% of the cases occurred during the first 6 months. After 24 months, the methimazole dose was lowered to 5 mg/day, and after this time point, no further adverse drug reactions were recorded. Skin reactions were the most prominent reaction, comprising 68% of the registered reactions, and no hepatic and bonemarrow affection was recorded. CONCLUSION: With this study, we report the frequency, timing of occurrence, and characteristics of adverse drug reactions when treating GH with the ATD drug methimazole for up to 48 months. Long-term low-dose methimazole treatment can be a cost-effective and straightforward treatment option if adverse drug reactions such as severe hepatic and bone marrow affection are kept in mind

Thyroid Function and Body Weight: A Community-Based Longitudinal Study

OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross-sectional population-based studies have repeatedly found that thyroid hormone levels, even within the normal reference range, might be associated with body weight. However, for longitudinal data, the association is less clear. Thus, we tested the association between serum thyrotropin (TSH) and body weight in a community-based sample of adult persons followed for 11 years. METHODS: A random sample of 4,649 persons aged 18-65 years from a general population participated in the DanThyr study in 1997-8. We included 2,102 individuals who participated at 11-year follow-up, without current or former treatment for thyroid disease and with measurements of TSH and weight at both examinations. Multiple linear regression models were used, stratified by sex and adjusted for age, smoking status, and leisure time physical activity. RESULTS: Baseline TSH concentration was not associated with change in weight (women, P = 0.17; men, P = 0.72), and baseline body mass index (BMI) was not associated with change in TSH (women, P = 0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly associated in both sexes. Weight increased by 0.3 kg (95% confidence interval [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a determinant of future weight changes, and BMI was not a determinant for TSH changes, but an association between weight change and TSH change was present

Predictors of Initial and Sustained Remission in Patients Treated with Antithyroid Drugs for Graves’ Hyperthyroidism: The RISG Study

Purpose. To study predictors of attaining (part 1) and sustaining (part 2) remission in patients with Graves’ hyperthyroidism (GH) treated with antithyroid drugs (ATD). Methods. In the prospective first part, the included patients were treated with ATD until a prespecified definition of remission (thyrotropin > 0.4 mU/L and TSH-receptor antibodies (TRAb) ≤ 1. 0 IU/L in a patient receiving a methimazole dose ≤ 5 mg/day, on two occasions two months apart) was met, or for 24 months. In the second part, patients attaining remission in part 1 were randomized to treatment or observation and followed until relapse or for 24 months. Results. 173 patients completed study 1 and 53% attained remission. TRAb and age were the only significant predictors of remission. Patients with baseline TRAb below vs above 10 IU/L attained remission in 63% compared to 39%, and 5 months priorly (p<0.001). In study 2, 96.4% of the patients randomized to treatment (n=33) sustained remission compared to 66% in the observation group (n=33). Treatment arm was the only significant parameter (p<0.001) of sustained remission. Conclusion. Baseline TRAb was prognostic for attaining remission in GH. Consecutive TRAb measurements during treatment were not worthwhile, but a single measurement after 6-8 months in patients with initial TRAb < 10 IU/L could substantially shorten the treatment period in a subgroup of patients. Only 3.6% of the patients in remission experienced relapse during follow-up when treated with a combination of fixed low dose methimazole and L-T4. ClinTrial.gov registration number is  NCT00796913

Is serum TSH a biomarker of thyroid carcinoma in patients residing in a mildly iodine-deficient area?

PURPOSE: To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid carcinoma (DTC) in a mildly iodine-deficient area.METHODS: Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortification program in Denmark.RESULTS: Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years] were included. S-TSH was significantly higher in the DTC group [median (IQR): 1.3 (0.9-1.9 mIU/L)] compared with the benign TND group [0.9 (0.6-1.5 mIU/L)] (p &lt; 0.0001). The median s-TSH in the background population was similar to that found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p &lt; 0.0001). There was no association between s-TSH and DTC disease stage (p = 0.08-0.87).CONCLUSIONS: s-TSH was significantly higher in patients with DTC than in those with benign TND. However, this difference can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.</p