Initial Disease Severity and Methimazole Titration for Graves’ Disease: A Retrospective Longitudinal Cohort Study

Abstract Context Graves’ Disease (GD) is the most common cause of thyrotoxicosis. Medical therapy with methimazole is the most common way to treat GD, but it has a narrow and dynamic therapeutic index, requiring frequent monitoring for titration. It is unclear how much initial disease severity (IDS) affects titration patterns. Objective Identify associations between IDS with methimazole dose and thyrotoxicosis control after initiation of therapy. Design Retrospective longitudinal cohort study (2018–2024) Setting A single tertiary medical center Patients or Other Participants The study included 152 patients, aged 18 and older, diagnosed with GD. It encompassed 1432 encounters. Main Outcome Measure(s) The analysis focused on the association of IDS, age, and sex with average decrease in methimazole dose per encounter, biochemical thyroid status per encounter, time until first euthyroid encounter, and dose of methimazole after 180 days of treatment. Results IDS was positively associated with percentage dose reduction of methimazole per encounter (P = 0.012) and proportion of hypothyroid encounters (P = 0.0101). There was no association of IDS with the proportion of hyperthyroid encounters (P = 0.088), methimazole dose after 180 days (P = 0.222), nor time to first encounter with euthyroid status. Age and sex were not associated with changes in dose or biochemical thyroid status. Conclusions When given a larger dose of methimazole, patients with severe thyrotoxicosis from GD reach euthyroid status as quickly as other patients with GD. However, these patients have more lability in thyroid control and may benefit from more frequent monitoring. After 6 months, severity of initial thyrotoxicosis was not associated with methimazole dose.