Gender variation in PTH sensitivity and rhythmicity following growth hormone replacement in adult growth hormone-deficient patients.

Abstract

Adult GH deficiency (AGHD) is associated with osteoporosis and reduced bone turnover; factors improved by GH replacement (GHR), with men gaining greater benefit than women. Reduction in sensitivity of bone and kidney to the effects of PTH may underlie AGHD changes in bone turnover. We determined the gender difference in PTH target-organ sensitivity following GHR in AGHD patients. Twenty AGHD patients (10 men) were admitted to hospital before and after GHR initiation. Half-hourly blood samples were collected for PTH, calcium, nephrogenous cyclic AMP (NcAMP, marker of PTH activity), type-I collagen C-telopeptide (CTX, bone resorption marker) and procollagen type-I amino-terminal propeptide (PINP, bone formation marker). The 24-h mean PTH concentration decreased in both genders (P < 0.001), with maximal changes seen 6 and 12 months following GHR in men and women, respectively. Increases in 24-h mean NcAMP (P < 0.05), calcium (P < 0.001) and bone turnover markers (P < 0.001) occurred in both genders following GHR, with maximal changes at 1 month in men, but at 3 months for NcAMP, calcium and CTX and 12 months for PINP in women. Maximal NcAMP increase was higher in men (P = 0.009). Following GHR, PTH target-organ sensitivity increased in both genders, demonstrated by simultaneous reduction in PTH concentration and increase in NcAMP, calcium and bone turnover. In women, improvement in renal PTH sensitivity was delayed and reduced, and changes in bone turnover were delayed, with increase in bone resorption preceding bone formation. Both factors may contribute to the reduced bone mineral density (BMD) response to GHR observed in women.