Biphasic Amiodarone-Induced Thyroid Dysfunction: De Novo Hypothyroidism Followed by Delayed Type 2 Thyrotoxicosis: A Case Report.

Amiodarone disrupts thyroid function in 15% to 20% of patients through iodine overload and direct cytotoxicity, with amiodarone-induced thyrotoxicosis (AIT) classified as type 1 (iodine-driven excess synthesis in abnormal glands) or type 2 (destructive thyroiditis in normal glands). Type 2 AIT often manifests late or after drug discontinuation due to amiodarone's prolonged tissue persistence (terminal half-life 26-107 days, mean approximately 53 days), and biphasic patterns where hypothyroidism precedes thyrotoxicosis are rarely reported, particularly de novo in previously euthyroid patients. This case involved a 66-year-old man with paroxysmal atrial fibrillation and normal baseline thyroid function (thyroid-stimulating hormone [TSH] 2.5 mIU/L, free T4 1.1 ng/dL) treated with amiodarone 200 mg daily for 22 months (cumulative dose approximately 13,200 mg), who developed hypothyroidism (TSH 6.34 mIU/L), leading to amiodarone discontinuation and levothyroxine initiation. Nine months postdiscontinuation, subclinical hyperthyroidism emerged (TSH 0.066 mIU/L), prompting levothyroxine cessation, and 11 months postdiscontinuation, overt thyrotoxicosis presented with palpitations, 6.4 kg weight loss, and atrial flutter (TSH 0.008 mIU/L, free T4 3.24 ng/dL, free T3 6.8 pg/mL). Negative thyroid autoantibodies and ultrasound showing diffuse thyromegaly with reduced parenchymal vascularity on color flow Doppler supported a type 2 AIT diagnosis, as this imaging feature is most specific for distinguishing subtypes. Thionamide therapy proved ineffective, but prednisone (40-50 mg daily, tapered over 4 months) restored euthyroidism within 4 months. This case demonstrated sequential dual toxicity in a typical thyroid, with type 2 AIT emerging nearly 1 year postdiscontinuation, highlighting the need for extended postdiscontinuation monitoring in select cases pending prospective data.