RESUMEN
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.
RESUMEN
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.
RESUMEN
Resting oxygen consumption and energy expenditure is sensitive to slight alterations in thyroid function. This means that timing and magnitude of cold adaptation would to some extent depend on thyroid function. Local thyroid hormone metabolism is important for energy expenditure and dissipation of heat in special tissues. Recruitment of brown adipocytes and upregulation of uncoupling protein 1 in mitochondria depends on high tissue T3 concentrations. Most of this T3 is derived from local 5' deiodination of T4. Brown fat is vital for cold exposed mice and rats, and may be important for temperature adaptation in human neonates. The role of thyroid hormone metabolism in adult human cold adaptation has not been finally clarified. Hypothetically, cold exposure may enhance T3 production by deiodination of T4 in skeletal muscle, which may enhance heat production in muscle via a change in muscle fiber type. Another hypothetical possibility is recruitment of brown adipocytes embedded in white adipose tissue in human adults. Understanding cold adaptation in human adults may lead to development of new drugs against obesity.