Reduction of the pituitary GH releasable pool in short children with GH neurosecretory dysfunction

OBJECTIVES The classical 'GH neurosecretory dysfunction' (GHNSD) refers to slowly growing children with normal GH responses to classical provocative t ests but impaired spontaneous GH secretion over 24 h frequently leading to low IGF-I levels. Thus it has been assumed that these subjects have insuffi ciency of spontaneous GH secretion due to neuroendocrine abnormalities in s pite of a normal releasable pool of GH. However, classical provocative test s do not reliably assess the maximal somatotroph capacity; thus it is still unclear if the GH pool is really preserved or not. GHRH + arginine test is more potent than the classical tests and evaluates the maximal secretory c apacity of somatotroph cells. The GH response to this stimulus is reproduci ble and also independent of age and puberty. DESIGN AND PATIENTS We studied the GH response to GHRH (1 mu g/kg iv) + arg inine (ARG, 0.5 g/kg iv) in 19 short children with GHNSD (14 boys and 5 gir ls, age: 12.1 +/- 0.7 years, pubertal stages I-III, HV-SDS between -1.6 and -4.9; GH peak > 10 mu g/l after classical stimuli but mean GH concentratio n (mGHc) < 3 mu g/l). The results in GHNSD were compared with those in 38 s hort children with idiopathic or organic severe GHD (GHD, 29 boys and 9 gir ls, age: 11.2 +/- 0.6 years., pubertal stages I-III, HV-SDS between -1.8 an d -4.4; GH peak < 10 mu g/l after 2 classical provocative tests) and in 83 children with normal or familial short stature (NC, 59 boys and 24 girls, a ge: 11.5 +/- 0.3 years., pubertal stages I-III; HV-SDS > 25th centile, norm al IGF-I levels). RESULTS Mean IGF-I levels in GHNSD (121.9 +/- 20.3 mu g/l) were lower (P < 0.001) than those in NC (270.3 +/- 13.8 mu g/l) but higher (P < 0.001) than those in GHD (72.0 +/- 4.0 mu g/l). The mean GH concentration (mGHc) in GH NSD (2.1 +/- 0.1 mu g/l) was lower (P < 0.01) than that in NC (4.9 +/- 0.5 mu g/l) but higher (P < 0.01) than that in GHD (1.5 +/- 0.2 mu g/l). On the other hand, the mean peak GH response to GHRH + ARG in GHNSD (43.7 +/- 3.7 mu g/l) was markedly higher (P < 0.001) than that in GHD (8.2 +/- 0.9 mu g /l) but significantly lower (P < 0.01) than that in NC (60.4 +/- 2.7 mu g/l ). All GHD patients had peak GH responses to GHRH + ARG below the 3rd centi le limit of normality (20 mu g/l), while all GHNSD patients had peak GH res ponses within the normal range. No significant correlation was found betwee n GH peak after GHRH + ARG, mGHc and IGF-I levels in each group. CONCLUSION Our study demonstrates that short children with 'GH neurosecreto ry dysfunction' show reduction in the GH releasable pool evaluated by the p rovocative and potent GHRH + arginine test. However, the peak GH response t o a single GHRH + arginine test in GH neurosecretory dysfunction is always within the normal range indicating that this test as well as classical stim uli does not distinguish normal subjects from GH neurosecretory dysfunction .