Journal of Clinical Endocrinology & Metabolism, Vol 65, 1177-1182, Copyright © 1987 by Endocrine Society

ARTICLES

Evaluation of hypothalamic dysfunction in growth hormone (GH)-deficient patients using single versus multiple doses of GH-releasing hormone (GHRH-44) and evidence for diurnal variation in somatotroph responsiveness to GHRH in GH-deficient patients

EA Schriock, JA Hulse, DA Harris, SL Kaplan and MM Grumbach
Department of Pediatrics, University of California, San Francisco 94143.

To examine the efficacy of multiple doses of GHRH-44 to enhance GH secretion and to determine the number of GHRH-44 doses required to exclude hypothalamic dysfunction, 12 doses of GHRH-44 were administered iv every 2 h to 4 GH-deficient patients beginning in the morning (group A) and to 4 GH-deficient patients beginning in the evening (group B). Five additional GH-deficient patients (group C) were given 4-18 GHRH-44 doses. The first and last doses were 5 micrograms/kg; all others were 1 microgram/kg. Higher GH responses were attained by 9 of the 13 patients after multiple GHRH-44 doses than after the initial GHRH-44 dose. After the first GHRH-44 dose, the peak plasma GH concentrations were less than 7 micrograms/L in 9 patients; 4 of 9 achieved GH concentrations above 7 micrograms/L after 5-7 GHRH-44 doses; 2 had measurable levels below 7 micrograms/L. GH concentrations remained undetectable in 3 older patients in group C. In the patients who had detectable GH levels after GHRH-44 treatment, serum somatomedin-C concentrations increased from 0.67 +/- 0.14 (+/- SEM) to 0.79 +/- 0.14 U/mL after 6 GHRH-44 doses (P less than 0.01; n = 10) then to 1.00 +/- 0.14 (+/- SEM) U/mL after an additional 4-6 GHRH-44 doses (P less than 0.05; n = 9). After 6 GHRH-44 doses in groups A and B, the integrated GH concentrations between 2000 and 0800 h were greater than the integrated GH concentrations between 0800 and 2000 h (P less than 0.02). These findings indicate that a hypothalamic defect cannot be excluded on the basis of an impaired response to a single dose of GHRH-44, that the number of GHRH doses required to stimulate GH release in GH-deficient patients is variable, and that in addition to the possibility of genetically determined GHRH insensitivity some non-responding patients have developed severe acquired resistance to GHRH. Evidence for diurnal variation in the responsiveness of somatotropes to GHRH-44 in GH- deficient patients was also found.

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