GROWTH-HORMONE RESPONSE TO GROWTH HORMONE-RELEASING HORMONE VARIES WITH THE HYPOTHALAMIC-PITUITARY ABNORMALITIES

Mie determined growth hormone (GH) and insulin-like growth factor I (I GF-I) levels after a 3 h infusion of escalating doses of growth hormon e-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypo pituitary patients with marked differences in pituitary features at ma gnetic resonance imaging (MRI) in order to evaluate further the contri bution of MRI in the definition of pituitary GH reserve in GH-deficien t patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were st udied, Group I comprised 13 patients: seven with isolated GH deficienc y (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI. Group II cons isted of eight patients with IGHD and small anterior pituitary/empty s ella, while in group III eight had IGHD and normal morphology of the p ituitary gland. Growth hormone and IGF-I levels were measured during s aline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1- 29) at escalating doses for 3 h: 0.2 mu g/kg at. 09.00-10.00 h, 0.4 mu g/kg at 10.00-11.00 h, 0.6 mu g/kg at 11.00-12.00 h and an intravenou s bolus of 2 mu g/kg at 12.00h. In the group I patients, the peak GH r esponse to GHRH(1-29) was delayed (135-180 min) and extremely low (med ian 2mU/l). In group II it was delayed (135-180 min), high (median 34. 8 mU/l) and persistent (median 37.4 mU/l at 18 5-210 min). In group II I the peak response was high (median 30.8 mU/l) and relatively early ( 75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 /- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impai red GH response to 3h of continuous infusion of escalating doses of GH RH(1-29) was strikingly indicative for pituitary stalk abnormality, st rengthening the case for use of GHRH in the differential diagnosis of GH deficiency, The low GH response, more severe in MPHD patients, migh t be dependent on the residual somatotrope cells, while the better res ponse (34.6 mU/l) in the group Ia patients might suggest that prolonge d GHRH infusion could help in evaluating the amount of residual GH pit uitary tissue. Pituitary GH reserve, given the GH response to GHRH inf usion in GH-deficient patients with small anterior pituitary/empty sel la, seems to be maintained.