GROWTH-HORMONE (GH) PROFILES IN RESPONSE TO CONTINUOUS SUBCUTANEOUS INFUSION OF GH-RELEASING HORMONE(1-29)-NH2 IN CHILDREN WITH GH DEFICIENCY

Six children presenting with partial growth hormone (GH) deficiency (m ean GH peak in two different tests. 8.0 +/- 1.3 mug/l) aged 8-10.3 yea rs (mean, 2.7 +/- 0.9 years) were treated for 6 months by continuous s ubcutaneous infusion of GH-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2 ); 24-hour GH profiles and height velocity were measured. A biphasic e ffect of GHRH(1-29)-NH2 infusion was observed. After an early substant ial increase in the 24-hour integrated concentration of GH, from 1.6 /- 0.1 to 3.5 +/- 0.7 mug/l/minute, a subsequent consistent decrease o ccurred by 3 months, which was more pronounced after 6 months (mean 24 -hour integrated concentration of GH, 1.9 +/-9 mug/l/minute). This eff ect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 mug/l dur ing a 24-hour period. No correlation was found between these changes a nd height velocity. Three children did not grow significantly, the oth er three children who had a growth response to GHRH(1-29)-NH2 were tho se with the lowest 24-hour integrated GH concentration at the end of t he study. The possible mechanisms involved in this biphasic effect, in cluding GHRH antibodies, changes in somatostatin levels and/or desensi tization of pituitary GHRH receptors, have been investigated.