Thyrotropin hyperresponsiveness to TRH despite hyperthyroxinemia in amiodarone-treated subjects

Abstract

Pituitary responsiveness to TRH was assessed prospectively over 24 weeks, in 15 patients receiving 300 mg amiodarone a day. All developed significant hyperthyroxinemia (both total and free), and marked elevations in reverse T 3 compared to pretreatment levels. Although basal TSH levels were unchanged in all of them, TSH responses to TRH increased by >50% when compared to pretreatment responses, in eight patients, while they remained unchanged (±15%) in the remaining seven. All eight with exaggerated responses also showed significant reductions ( P < .001) in plasma levels of total and free T 3, whereas in the seven who did not show any increase in TSH responses, T 3 levels were unchanged. The increase in TSH response to TRH was strongly correlated ( r = −.82, P < .001) with T 3 levels. Total and free T 4 levels were equally elevated in both groups. These observations indicate that amiodarone effectively blocks the suppressive effect of hyperthyroxinemia on TSH secretion, and that T 3 is the mediator of thyroid feedback control in amiodarone treated patients.