Recovery of Bone Mineral Density after Surgical Cure, but not by Ketoconazole Treatment, in Cushing’s Syndrome

Abstract:

The aim of our study was to retrospectively assess the effect of treatment on bone mineral density (BMD) in patients with Cushing’s syndrome. Nineteen patients (17 women, 2 men; mean age ± SD, 41 ± 10 years; preoperative duration of disease 20 ± 15 months) were studied. Six patients had a cortisol-producing adenoma and 13 had pituitary-dependent bilateral adrenal hyperplasia. BMD of the lumbar spine (L2–L4) was measured by dual-energy X-ray absorptiometry just before and 1–10 years after adrenalectomy or pituitary adenomectomy. Patients were divided in two groups. The first group of 9 patients (6 adrenal and 3 pituitary adenomas; group A) included those treated successfully by surgery (>5 years follow-up in the case of pituitary surgery). The second group of 10 patients (group B) included those treated with the steroidogenesis inhibitor ketoconazole, 300–600 mg/day, after unsuccessful pituitary surgery. In group A, restoration of normal cortisol was associated with a significant increase in BMD (from 829 ± 112 mg/cm² to 952 ± 107 mg/cm²; p = 0.002). In group B, no changes in BMD were observed (from 857 ± 160 to 847 ± 163 mg/cm²), in spite of markedly decreased or normalized cortisol levels during ketoconazole treatment. These findings indicate that definitive correction of hypercortisolism restores BMD to normal levels in patients with Cushing’s syndrome. In patients treated with ketoconazole after unsuccessful pituitary surgery, even when normalization of cortisol levels was achieved, BMD remained low. This would suggest an interfering effect of this drug on bone metabolism.