Efficacy of tablet glucocorticoids depending on their starting dose in patients with type 2 amiodarone-induced thyrotoxicosis: a prospective randomized study

Abstract

Background: Glucocorticoids are the first-line pharmacotherapy for amiodarone-induced destructive thyroiditis. Despite the availability of clinical guidelines, there is no unified approach to patient management (indications for prescription, starting dose, duration of therapy and withdrawal algorithm). The issues of dose-dependent effect of glucocorticoids, verification of factor of delayed treatment response, prediction of severity and duration of thyrotoxicosis remain unresolved. Aim: To evaluate the efficacy of various regimens of tablet glucocorticoids in patients with type 2 amiodarone-induced thyrotoxicosis. Methods: This was a prospective randomized open-label comparative controlled trial of the efficacy of two starting doses of prednisolone 30 mg (n = 22) and 60 (n = 22) mg daily. The study groups were comparable for gender (men to women ratio 2:1), age, anthropometric and main clinical and laboratory characteristics. After euthyroidism has been achieved, thyroid function was assessed twice at 1 and 2 months during the dose reduction and at 1, 3, 6, 9, and 12 months after prednisolone withdrawal. The follow up was 15 to 24 months. The efficacy of therapy was evaluated by the time to euthyroidism, thyrotoxicosis duration, rate of recurrent waves of destruction and relapses. We looked for predictors of delayed treatment response and severe and prolonged thyrotoxicosis. Results: There were no significant differences in the time to euthyroidism (Mantel-Cox log rank test 0.859), duration of thyrotoxicosis (Mantel-Cox log rank test 0.813), rate of recurrent waves of destruction (0.721) and relapses (0.464). Within 30 days of therapy, remission was obtained in 11/22 (50.0%) patients in active control group (prednisolone 30 mg) and in 12/22 (54.5%) patients in the 60 mg group. Delayed response ( 60 days) was defined by recurrent waves of destruction (RR = 34.7, 95% CI: 3.7–321.8; R² = 0.430; p = 0.002). High risk of severe thyrotoxicosis was predicted by the age ≤ 54 years (AUC 0.749 ± 0.095, 95% CI: 0.562–0.936; p = 0.038; sensitivity 71.4%, specificity 62.2%). The duration of thyrotoxicosis was associated with body mass index (B = -7.4, R = 0.481, R² = 0.0231; p = 0.024) and cumulative amiodarone dose (B = 0.4, R = 0.472, R² = 0.223; p = 0.026). A combination of adverse events (hyperglycemia, infection, proximal myopathy, change in appearance, hematomas) and their severity were more frequent in the patients who had received the 60 mg prednisolone starting dose (p = 0.014). Conclusion: Compared to lower doses, the use of high doses of glucocorticoids is associated with a greater severity of side effects and does not ensure any significant acceleration of thyrotoxicosis remission. The potential factors of unfavorable clinical course of type 2 amiodarone-induced thyrotoxicosis are age, body mass index, and cumulative dose of amiodarone.