The adverse consequences of growth hormone (GH) deficiency (GHD) on bone growth in children is well described. Whether adult GHD is associated with bone loss is unknown. We evaluated 14 patients with hypothalamic-pituitary tumors (HPT) acquired during adulthood (5 men, 9 women; mean age = 48.1 +/- 4.6 years; mean BMI = 28.8 +/- 1.7) and 14 age-, sex-, and weight-matched controls. Nine HPT patients were receiving gonadal steroid replacement therapy for a mean of 11 years. All subjects had basal IGF-I and IGFBP-3 levels prior to testing with GH-releasing hormone [1 microgram/kg IV bolus; responses expressed as maximum percentage increase above baseline (PERGH)]. Bone mineral density (BMD) of the spine, hip, and total body were measured by dual-energy X-ray absorptiometry. Mean BMD Z-scores of the HPT patients were significantly lower in the femoral neck, Ward's triangle, and trochanter than in controls (all P < 0.05). Mean total body BMD (g/cm2) was also lower in the patient group (1.04 +/- 0.03 versus 1.13 +/- 0.03, P < 0.05). For the subgroup of HPT patients receiving conventional gonadal steroids, mean BMD Z-scores of the lumbar spine also were significantly lower than controls (-1.84 +/- 0.43 versus -0.57 +/- 0.46, P < 0.05). PERGH and IGF-I were correlated with Z-scores of the femoral neck (r = 0.47, P < 0.01; r = 0.45, P < 0.01) and Ward's triangle (r = 0.47, P < 0.01; r = 0.41, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)