CIRCULATING IMMUNOREACTIVE GROWTH-HORMONE RELEASING HORMONE CONCENTRATIONS AND GROWTH-HORMONE RESPONSE TO GROWTH-HORMONE RELEASING HORMONE IN SHORT CHILDREN

To study the role of peripheral immunoreactive growth hormone releasin g hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6-16.3 years) and a mean relative heig ht score of -3.2 SD (range -5.0-2.1 SD) were investigated. The childre n were divided into prepubertal (n = 35) and pubertal (n = 11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1 ) GH deficient subjects (maximal GH < 10 mu g/l in both tests); (2) di scordant responders (maximal GH < 10 mu g/l in one test and 1 10 mu g/ l in the other); and (3) normal responders (maximal GH > 10 mu g/l in both tests). Peripheral ir-GHRH concentrations were measured during th e IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into roup 3. Children in group 1 were older than those in group 3. There were no significant cant differences in r elative heights and weights or absolute and relative growth velocities between the groups. Subjects in, groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant dif ferences in the basal plasma ir-GHRH concentrations between the groups . Nine children (19.6%) had somatotrophs with a poor response to a sin gle dose of exogenous GHRH (maximal GH < 10 mu g/l). These subjects ha d increased basal plasma ir-GHRH concentrations. All of them had a dec reased GH response to IIH and/or clonidine. Pubertal children had high er circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r = -0.46; P < 0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observati ons suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating co mplementary evaluation of their spontaneous GH secretion ; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH respon ses in pharmacological tests respond normally to GHRH and (4) the pitu itary sensitivity to GHRH decreases with increasing age. Peripheral ir -GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature . The GHRH test is of limited value in the diagnosis of GHD, since a n ormal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.