1Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool. L7 8XP; 2Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool. L69 3GA.
BACKGROUND: Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Growth Hormone replacement (GHR) results in increased bone mineral density (BMD), with greater benefit derived in men. PTH plays an important role in bone metabolism and reports suggest that bone and renal insensitivity to PTH may contribute to changes in bone turnover in AGHD.
OBJECTIVES: To determine the gender difference in PTH, phosphocalcium metabolism and bone turnover response to GHR in AGHD.
METHODS: 16 patients (8 men) with AGHD were consented to the study. Half-hourly blood and 3-hourly urine samples were collected at baseline, and 1, 3, 6 and 12 months following GHR, for PTH, calcium, phosphate, nephrogenous cAMP (NcAMP, marker of PTH activity), bone resorption markers (serum CTx and urinary NTx) and bone formation marker (serum PINP). Local Ethical Committee approval was obtained.
RESULTS: 24-hour mean PTH decreased similarly in both genders (p<0.001) to 6 months, and continued to decrease in women at 12 months (p<0.001). NcAMP and serum phosphate increased in both genders (p<0.02), with greater percentage changes in men (p<0.001). Serum calcium increased in both genders (p<0.001), with a greater percentage change in women (p<0.001). Urinary calcium and phosphate decreased in men (p=0.045), but not women. Bone markers increased simultaneously between 0 and 3 months in men (p<0.001) and remained above baseline at 12 months. In women, CTx and NTx significantly increased from 1 month (p<0,001), while PINP increased significantly from 3 months (p<0.001).
CONCLUSION: The significant differences we observed, between genders, in PTH, NcAMP and phosphocalcium response to GHR, suggest increased end-organ responsiveness to the effects of PTH, in addition to increased direct GH effect, in men compared to women. In women, bone resorption preceded bone formation, contrasting the simultaneous increase demonstrated by men. These factors may explain the gender difference in BMD response to GH.