Biochemical Characteristics, Treatment, and Outcomes of Thyrotoxicosis in Amiodarone-Treated Individuals with Prior Hypothyroidism

Background Evidence regarding the transition from hypothyroidism to thyrotoxicosis in amiodarone-treated patients remains scarce. We compared clinical characteristics, treatments, and outcomes of amiodarone-exposed individuals developing thyrotoxicosis following hypothyroidism (post-hypo-T) versus those without prior thyroid disease (T-controls). Methods This retrospective cohort study utilized electronic health records from a large health maintenance organization (HMO). We included adults from the cardiovascular disease registry with new-onset thyrotoxicosis diagnosed between January 1, 2010, and December 31, 2022, who received amiodarone within the year preceding diagnosis. Follow-up ended on August 31, 2025. Cox regression models adjusted for age and sex were used to analyze outcomes. Results Of 558 individuals, 91 (16%) had prior hypothyroidism and 467 were controls. Post-hypo-T patients were older (70.4±10.1 vs. 67.4±11.0 years; p = 0.02) and had a higher proportion of males (44.0% vs. 25.3%; p < 0.001). Median amiodarone exposure prior to diagnosis was 2.7 versus 2.8 years, respectively (p = 0.01). At diagnosis, post-hypo-T individuals had lower median free thyroxine (fT4) levels (27.0 vs. 31.3 pmol/L; p < 0.001) and free triiodothyronine (fT3) levels (6.4 vs. 7.5 pmol/L; p < 0.001). Over a 7.8-year median follow-up, antithyroid medications were used less frequently in post-hypo-T individuals (37.4% vs. 54.0%; p = 0.004). Glucocorticoid use was numerically lower in post-hypo-T individuals (26.4% vs. 38.5%; p = 0.06). Post-hypo-T individuals had a higher incidence of hypothyroidism requiring levothyroxine (64.8% vs. 17.8%; p < 0.001). Conclusions Among amiodarone-exposed individuals who develop thyrotoxicosis, those with prior hypothyroidism have a milder biochemical presentation, less frequent use of antithyroid drugs or glucocorticoids, and a higher likelihood of recurrent hypothyroidism requiring levothyroxine.