Low bone mineral density in adults with previous hypothalamic-pituitary tumors: Correlations with serum growth hormone responses to GH-releasing hormone, insulin-like growth factor I, and IGF binding protein 3

Summary

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 hypothalamicpituitary tumors (HPT) acquired during adulthood (5 men, 9 women; $\bar x$ age=48.1±4.6 years; $\bar x$ 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 μg/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-l 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). These results indicate that adults with previous HPTs have significantly lower spine and hip BMD compared with healthy controls, regardless of gonadal steroid therapy, and that this premature bone loss is associated with relative GHD. IGF-I and PERGH measurements might be useful markers to identify such patients at risk for reduced BMD.