Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children

Abstract

Objective. Graves' disease is the most common cause of hyperthyroidism in the pediatric population. Antithyroid medications used in children and adults include propylthiouracil (PTU) and methimazole (MMI). At our center we have routinely used MMI for Graves' disease therapy. Our goals are to provide insights into adverse events that can be associated with MMI use. Methods. We reviewed the adverse events associated with MMI use in our last one hundred consecutive pediatric patients treated with this medication. Results. The range in the patient age was 3.5 to 18 years. The patients were treated with an average daily dose of MMI of 0.3+/-0.2 mg/kg/day. Adverse events attributed to the use of the medication were seen in 19 patients at 17+/-7 weeks of therapy. The most common side effects included pruritus and hives, which were seen in 8 patients. Three patients developed diffuse arthralgia and joint pain. Two patients developed neutropenia. Three patients developed Stevens-Johnson syndrome, requiring hospitalization in 1 child. Cholestatic jaundice was observed in 1 patient. No specific risk-factors for the development of adverse events were identified. Conclusions. MMI use in children is associated with a low but real risk of minor and major side effects.

Graves' Disease Presenting with Severe Cholestasis

“…Of note, the patient had resolution of both the hyperthyroidism and cholestasis while treated with methimazole, an agent known to, on occasion, cause cholestasis (13)(14)(15). Propylthiouracil was not used for treatment due to recent publications reporting higher rates of hepatotoxicity in children (16).…”

MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves’ disease

“…ANCA-positive vasculitis occurs only in exceptional cases, and susceptibility to this condition seems to be higher in patients of Asian origin (26). The risk appears to increase with the duration of PTU therapy, following the opposite pattern to other adverse effects of ATDs, which typically occur during the first 3-6 months of treatment (25,26,27). In adults, MMI/CMZ use has also been shown to be associated with ANCA positivity, although the risk for this combination is lower than that reported for PTU (26,28).…”

“…The use of ATDs, such as MMI/CMZ or PTU, is associated with an increase in the risk of some minor reversible adverse reactions (such as skin rash, urticaria, arthralgia and less frequently, gastrointestinal problems) in approximately 5-25% of cases, requiring concomitant transitory antihistamine treatment in some cases, and the risk of much rarer severe skin reactions (Stevens-Johnson syndrome) (25). The frequency of agranulocytosis, the most severe side effect, is between 0.2 and 0.5% for both drugs.…”

Lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy

“…StevensJohnson syndrome was diagnosed in three of these patients, one of which required hospitalization. 19,20 Another study, focusing on hepatic and cutaneous side effects of ATDs, found an increase in the frequency of dermatological reactions in patients taking 30 mg/day MMI as compared to those taking MMI at lower dosages and PTU 300 mg/day. 21 The authors also showed that patients who experienced side effects with an ATD did not have an increased tendency to develop adverse reactions after switching to another medication of the same class.…”