Endocrine Abstracts

Introduction: The simultaneous occurrence of two drug-induced thyroid dysfunctions is rare. We present a case of central hypothyroidism due to bexarotene (BXC), followed by Interferon-α (IFNα)-induced Graves’ disease (GD) thyrotoxicosis after 2 years.

Case Report: A 56-year-old man with no prior thyroid disease was diagnosed with cutaneous T-cell lymphoma and commenced treatment with BXC 600 mg/day and IFNα 90 mg/week concurrently. After two weeks, TSH was <0.004 uUI/ml (0.4-4.0) and FT4 was <0.49 ng/dl (0.7-1.5). MRI revealed no selar or parasellar lesions. Central hypothyroidism due to BXC was diagnosed and levothyroxine (L-T4) was initiated at 50 mg/day, gradually reaching 88 mg/day (1.4 mg/kg/day). BXC dose was reduced to 300 mg/day due to severe hypertriglyceridemia and the therapy with IFNα was maintained. After 25 months, TSH remained <0.004 uUI/ml and FT4 was 2.04 ng/dl under L-T4 88 mg/day, which was reduced to 75 mg/day. Four months later, the patient exhibited weight loss, tremors, palpitations, and abnormal thyroid levels (TSH <0.004 uUI/ml, FT4 4.60 ng/dl, FT3 >20 pg/ml (1.8-4.2); anti-TPO antibodies 342 UI/ml (<5.6), TRAbs 30 U/l (<2). IFNα-induced GD was diagnosed. L-T4 was ceased and methimazole (MMI) 15 mg/day initiated. One week later his thyroid function was: TSH <0.004 uUI/ml, FT4 0.79 ng/dl (0.7-1.5), FT3 3.1 pg/ml (1.8-4.2). Recently the patient was under IFNα 90 mg/week and BXC 150 mg/day, maintaining unmeasurable TSH, a FT4 of 1.5 ng/dl and FT3 of 5.3 pg/ml on MMI 12.5 mg/day (increased to 15 mg/day). Unfortunately, the patient deceased at 58 years old due to the progression of the cutaneous T-cell lymphoma with neurolymphomatous involvement.

Conclusions: BXC leads to central hypothyroidism in 30% cases by decreasing TSH secretion and increasing peripheral thyroid hormone metabolism. L-T4 can be initiated with or after confirming reduced FT4 levels, with doses up to 3 mg/kg/day. IFNα can induce autoimmune (Hashimoto’s thyroiditis (HT) and GD) and non-autoimmune (non-autoimmune hypothyroidism and destructive thyroiditis) thyroid diseases via immune dysregulation, T cell activation, and direct follicular cell toxicity. IFNα-induced GD is less common than HT and destructive thyroiditis, often irreversible with dose reduction or cessation. In this case, diagnosing GD was delayed as TSH suppression was inherent to central hypothyroidism from BXC and since the initial FT4 elevation was interpreted as excessive L-T4 dosage. The gradual BXC dose reduction led to increased MMI dosage due to predominant IFNα-induced hyperthyroidism. Vigilant thyroid function monitoring during concurrent medication therapies causing thyroid dysfunction is crucial.