Elevated Serum Creatine Kinase During the Treatment of Patients with Graves’ Disease with Antithyroid Drugs: New Insights into an Old Issue

Serum creatine kinase (CK) elevation can occur in some patients with Graves' disease treated with antithyroid drugs (ATDs). This study retrospectively investigated clinical characteristics and biochemical data of patients with Graves' disease who experienced serum CK elevation during ATD treatment. CK elevation was observed in 29.6% (37/125) of patients, with 11.2% (14/125) being symptomatic. This incidence is higher than previously reported (13.5%). There were no differences in pre-treatment characteristics between patients with and without CK elevation. The intervals between the initiation of ATD treatment or normalization of thyroid function and the onset of CK elevation were 11.3±8.0 and 5.8±6.6 weeks, respectively, and peak serum CK levels averaged 441.9±394.0 IU/l. Markedly elevated serum CK were accompanied by increased serum myoglobin levels. Serum CK elevation occurred either continuously or intermittently, or as a single episode during the course of treatment. Thyroid function at the time of CK elevation varied from hyperthyroid to normal to hypothyroid. In conclusion, serum CK elevation in patients with Graves' disease treated with ATDs is not uncommon, with symptomatic cases accounting for approximately 10%, and the frequency increasing to around 30% when asymptomatic cases are included. The characteristics observed in our patients suggest the involvement of alternative, as yet unknown mechanisms beyond the relative hypothyroidism theory and the ATD side-effect theory in the development of CK elevation during ATD treatment in patients with Graves' disease.