Growth hormone secretagogues in children with altered growth

A diagnostic test was devised to evaluate pituitary growth hormone (GH) secretory potential. GH secretory dynamics were assessed in children with and without GH deficiency. The GH response was measured to GH-releasing hormone (GHRH) and the GH-releasing peptide GHRP-2, administered sequentially. The mean (+/- SEM) peak GH response to GHRP-2 was 20.1 +/- 5.5, 63.6 +/- 24.9 and 42.2 +/- 4.3 micrograms/l for GH-deficient, slowly growing non-GH-deficient and control children, respectively (p < 0.02 and p < 0.05 for GH-deficient vs controls and slowly growing children, respectively). Corresponding values for area under the curve (AUC) were 995 +/- 371. 2460 +/- 953 and 1598 +/- 274 micrograms/l x minute. Peak GH (and AUC) responses to GHRH were 19.6 +/- 5.1 micrograms/l (924 +/- 232 micrograms/l x minute), 31.4 +/- 8.4 micrograms/l (1544 +/- 449 micrograms/l x minute) and 39.8 +/- 7.8 micrograms/l (2201 +/- 437 micrograms/l x minute) for the same three groups, respectively (p < 0.05 for peak GH in GH-deficient patients vs controls, and p < 0.02 and p < 0.01 for AUC in GH-deficient vs slowly growing children and controls, respectively). The ratio of the peak GH response to GHRP-2 and GHRH was similar in all three groups. As these secretagogues stimulate different aspects of hypothalamic function (i.e., they are functional complements), robust GH secretion in response to GHRH or GHRP could suggest adequate endogenous GHRP or GHRH, respectively. A poor response to either GH secretagogue administered individually could represent inadequacy of its endogenous complement. The integrity of functional pituitary elements could be differentiated from inadequate complements by administering both GH secretagogues simultaneously. Application of these principles should allow a better definition of the underlying disorder and provide the basis for therapeutic strategies for those patients with abnormal GH production and/or secretion.