Hazards of ketoconazole therapy in testotoxicosis

An eight-year-old boy with Leydig cell hyperplasia (testotoxicosis) was admitted with a three-day history of rash, vomiting and diarrhoea, followed by acute onset of breathlessness and confusion. He was shocked, with liver cell and renal failure, erythematous rash and severe interstitial pneumonitis. He had been treated with ketoconazole for four years prior to admission, receiving 1200 mg daily during the preceding year. Cessation of ketoconazole therapy was associated with full clinical recovery but relapse of testotoxicosis. Ketoconazole was reintroduced cautiously at a lower dose, with no ill-effect, and reasonable control of testotoxicosis. We conclude that this boy's illness, including the interstitial pneumonitis, represented a reaction to ketoconazole which was dose-related rather than idiosyncratic.