Impact of severe hypothyroidism on cyclophosphamide disposition and routes of metabolism and transport in a patient with treatment-resistant lupus nephritis.

Objective: To report what we believe to be the first case of severe hypothyroidism with reduced drug metabolism and transport activity.

Case Summary: A 32-year-old African American woman with a history of treatment-resistant lupus nephritis and concurrent hypothyroidism was participating in a clinical study to evaluate cyclophosphamide pharmacokinetics in patients with glomerulonephritis due to lupus nephritis and small-vessel vasculitis. Thyroid-stimulating hormone levels ranged from 60 to 300 μIU/mL, despite high doses of thyroid replacement hormone (levothyroxine 400 μg twice weekly).