Effects of pulsatile administration of growth hormone (GH)-releasing hormone on short term linear growth in children with GH deficiency

Abstract

To assess the efficacy of GH-releasing hormone (GHRH) in the treatment of GH deficiency, we measured the effects of pulsatile iv GHRH administration on GH secretion, plasma levels of somatomedin-C (SmC), and short term linear growth (as determined by lower leg measurements) in seven GH-deficient children in a placebo-controlled study. Either GHRH, at a dose of 1 microgram/kg (seven patients), or 0.9% saline (NS; four of these patients) was given iv every 3 h for 9-12 days; all patients also received GH for a similar period. Lower leg length was measured every 3 weeks before and after each treatment. GHRH was more effective than placebo in accelerating linear growth (P less than 0.05). The responses, however, were heterogeneous; four of the children responded with accelerated growth, and three did not. Two of the children who failed to grow had no increase in plasma GH or SmC during GHRH administration, and one had an attenuated GH response. The four children who grew had induction of pulsatile GH secretion [mean peak GH, 10.4 +/- 1.3 (+/- SEM) ng/ml after GHRH vs. 1.5 +/- 0.5 ng/ml after NS; P less than 0.05] and elevation in SmC levels (maximum, 0.5 +/- 0.1 U/ml during GHRH vs. 0.19 +/- 0.05 during NS; P less than 0.01). The lower leg growth velocity during GHRH treatment (2.8 +/- 0.2 mm/3 weeks) was greater than their own basal rate (0.6 +/- 0.2 mm/3 weeks; P less than 0.01) or their growth during placebo treatment (0.4 +/- 0.2 mm/3 weeks; P less than 0.01). Thus, repeated administration of GHRH stimulated increases in GH and SmC in some but not all GH-deficient children. The growth response appears to be related to the magnitude of the GHRH-stimulated rise in GH levels. GHRH increases short term linear growth in some children with GH deficiency and holds promise as an alternative to GH as a form of therapy in these patients.