Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

Abstract

Objective: To analyze the effectiveness and reproductivity of a challenge with clonidine (CLO) plus GHRH administration to establish a state of GH-deficiency and the causes of it. Methods: 24 children (17M, 7F) with stature <1 or 2 SD from P3, previously studied with different classical tests, were given CLO (150 μg/m2 orally, at time 0’) plus GHRH (60’ later, 1 μg/kg, iv). This test was repeated but giving placebo at time 0’. For comparison purposes, 20 agematched normal children (14M, 6F) were studied. Growth velocity (GV) and bone age (BA) before performing CLO +GHRH were considered. Results: While classical GH tests show a great variability of negative or positive GH responses in the same short patient, all but two patients significantly responded to CLO+GHRH (GH peak: 42.2 ± 19 vs. 41.6 ± 3.5 in controls). Controls showed a significant positive correlation between the amplitude of GH response and chronological and bone age (R=0.832; F=37.6; P=0.001, multiple regression analysis): y=a+b × BA+c × CA, where y=GH peak, BA=bone age, CA=chronological age, and a, b and c are constants. This equation allows to establish the value of GH peak theoretically obtained after CLO+GHRH challenge in a normal child. Applying this equation to the responses to CLO+GHRH in short children a deviation, ranging between -435% and +41%, was obtained between theoretical and real GH peaks (%DT-R). Responses between -20% to +20% were considered normal. Plotting these responses (% DT-R) against the SD of the mean of the BA to GV ratio in normal children, five populations were defined: 1) Low response and low GV for BA; 2) Low response and normal GV for BA; 3) Normal response and low GV for BA; 4) Normal response and normal GV for BA; and 5) High response and low GV for BA. Conclusion: The test CLO+GHRH is safe, effective and unique to detect GH-deficiency and its causes in short children and adults.