Endocrine Abstracts

Aim: Antithyroid drugs (ATD) methimazole and propylthiouracil (PTU) are the drugs of choice for treatment of hyperthyroidism. Agranulocytosisis, the most severe side effect of these medications, occurs in 0.2–0.5% of patients. ATDs are used also in patients with amiodarone-induced thyrotoxicosis (AIT). Our objective was to evaluate the risk for agranulocytosis, associated with ATDs, in patients with AIT, and to compare the risk with the risk of ATD-associated agranulocytosis in thyrotoxicosis due to other etiologies.

Methods: A retrospective cohort study within Clalit Health Care database was conducted of all patients with thyrotoxicosis, newly treated with ATD between 1.1.2002-31.12.2015 and followed until 3 months from the last ATD prescription dispensing, or an event of agranulocytosis. High ATD dose was defined if either methimazole or PTU was administered in an average daily dose above the median dose for that drug.

Results: The cohort included 14,781 patients with thyrotoxicosis treated with ATDs. 39 patients (0.3% of the cohort) developed agranulocytosis during 40,551 years of follow-up: incidence rate 9.62 (6.84–13.15) for 10,000 years of follow up. Mean follow-up time was 2.7 years (S.D. 3.1 years). Agranulocytosis occurred after a median of 55 days. Higher ATD dose was independently associated with higher risk for agranulocytosis HR 3.53 (1.64–7.63) regardless of amiodarone. Age was also associated with increased agranulocytosis risk in univariate Cox regression analysis with HR=1.02 (1.01–1.04) for each 1-year increase. Five hundred ninety three of 14,781 patients were treated with amiodarone at cohort entry. 1.3% of AIT patients developed agranulocytosis on ATD therapy, as opposed to only 0.2% of patients with thyrotoxicosis due to other etiologies. In a Cox regression multivariable model amiodarone treatment at cohort entry was associated with significantly higher risk for developing agranulocytosis during ATD treatment independently of dose and age, HR 5.15 (2.10–12.60).

Conclusion: AIT patients are at increased risk for ATD-associated agranulocytosis. Higher ATD dose is an independent risk factor for agranulocytosis. We suggest closer monitoring of ATD-treated AIT patients for agranulocytosis, and initiation with lower ATD dose in AIT patients, reserving dose escalation for irresponsive cases.