Effects of Growth Hormone Replacement on Parathyroid Hormone Sensitivity and Bone Mineral Metabolism

Abstract

Adult GH deficiency (AGHD) is associated with reduced bone mineral density, and decreased end-organ sensitivity to the effects of PTH has been suggested as a possible underlying mechanism. We investigated the effects of GH replacement (GHR) on PTH circulating activity and its association with phosphocalcium metabolism and bone turnover in 16 (8 men and 8 women) AGHD patients. Half-hourly blood and 3 hourly urine sampling was performed on each patient over a 24-h period before GHR and then after 1, 3, 6, and 12 months of GHR. GH was commenced at a dose of 0.5 IU/d and was titrated to achieve and maintain an IGF-I SD score within 2 SD of the age-related reference range. The target IGF-I SD score was achieved within 3 months and was maintained at 12 months after GHR in all patients. Our results demonstrated a significant decrease in serum PTH at all visits after GHR compared with baseline values (P < 0.001), with a concomitant increase in nephrogenous cAMP excretion at 1 (P < 0.001) and 3 (P < 0.05) months and increases in serum calcium (P < 0.001), serum phosphate (P < 0.001), 1,25-dihydroxyvitamin D(3) (P < 0.001), type I collagen C-telopeptide (a bone resorption marker; P < 0.001), and procollagen type I amino-terminal propeptide (a bone formation marker; P < 0.001). Simultaneously, we observed a significant decrease in urinary calcium excretion (P < 0.001) and an increase in maximum tubular phosphate reabsorption (P < 0.001). Together these results suggest increased end-organ responsiveness to the effects of circulating PTH resulting in increased bone turnover and reduced calcium excretion. Significant circadian rhythms were observed for serum PTH, phosphate, type I collagen C-telopeptide, and procollagen type I amino-terminal propeptide before and after GHR. However, sustained PTH secretion was observed between 1400-2200 h, with a reduced nocturnal rise in untreated AGHD patients, whereas PTH secretion decreased significantly between 1400-2200 h (P < 0.001), with a significant increase in nocturnal PTH secretion (P < 0.001) after 12 months of GHR. Our results demonstrate that GH may have a regulatory role in bone mineral metabolism, and our data provide a possible underlying mechanism for the development of osteoporosis in AGHD patients. The changes observed after GHR may further explain the beneficial effects of GHR on bone mineral density that have consistently been reported.

Parathyroid responsiveness to hypocalcemic and hypercalcemic stimuli in adult growth hormone deficiency after growth hormone replacement

“…These findings were associated with low bone turnover and changes in phosphocalcium metabolism in untreated AGHD patients, suggesting decreased end-organ sensitivity to the effects of PTH (2). In a more recent study (4), we demonstrated that growth hormone replacement (GHR) significantly decreases PTH concentration with changes in PTH secretory pattern and a significant increase in NcAMP. In addition, we observed a significant increase in bone turnover and changes in phosphocalcium metabolism, suggesting an increase in end-organ sensitivity to PTH.…”

Circadian rhythm of circulating sclerostin in healthy young men

“…3,4 •Circadian rhythm parameters evaluated were: 1) midline estimate statistic of rhythm (MESOR), rhythm-adjusted mean; 2) amplitude and 3) acrophase.…”

Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency

“…over that of 24,25(OH)2D3 with a moderate increase in intestinal Ca absorption in dogs (27). In a study in GHD humans, GH administration at bedtime caused a nocturnal increase in PTH production followed by a decrease in PTH during daytime as compared with untreated GHD adults (28). It could be hypothesized that such a 24-h PTH pattern during GH therapy could be beneficial for bone density.…”