Growth Hormone Deficiency Is Not Associated with Impaired Vagal Cholinergic Nervous System Activity in Children

Abstract

ABSTRACT. Central cholinergic mechanisms mediate release of growth hormone (GH) as well as peripheral secretion of pancreatic polypeptide (PP). To determine if impaired ability to secrete GH is associated with defective P P response, we studied the PP, epinephrine, and norepinephrine responses to insulin-induced hypoglycemia in 31 children evaluated for GH deficiency by insulin-arginine stimulation (IATT) and 24-h integrated concentrations of GH (IC-GH). Eleven patients had normal GH by IATT and IC-GH (controls), 10 patients had normal GH by IATT but subnormal IC-GH, 10 patients had GH deficiency by both IATT and IC-GH. P P levels peaked at the time of glucose nadir, and remained elevated for 20 min thereafter. The peak P P and incremental P P change from baseline were not significantly different among the three groups. The log peak P P response was inversely correlated with the glucose nadir ( r = -0.5, p < 0.005). Peak P P levels were also significantly correlated with the peak epinephrine levels ( r = 0 . 6 ,~ < 0.001) but not with norepinephrine.Our findings suggest that 1 ) GH deficiency disorders are not associated with impaired vagal cholinergic response to hypoglycemia; 2) in children the magnitude of P P response is inversely related to the degree of hypoglycemia; and 3) the peripheral hormonal manifestation of autonomic nervous system responses to hypoglycemia as measured by P P and epinephrine levels are closely correlated. (Pediatr Res 24: 574-576,1988) Abbreviations GH, growth hormone PP, pancreatic polypeptide E, epinephrine NE, norepinephrine IC, integrated concentration hPP, human P P GHND, GH neurosecretory dysfunction GHD, GH deficiency Central cholinergic mechanisms mediate GH release (1, 2) as well as secretion of PP (3, 4). Cholinergic agonists potentiate the secretion of both GH and PP and conversely antagonists of cholinergic muscarinic receptors such as pirenzepine and atropine blunt the secretion of these hormones (1, 5). We tested the hypothesis that children with impaired GH secretion might also have impairment of vagal cholinergic activity, manifested by deficient PP secretion. During insulin-induced hypoglycemia which is a potent stimulant for PP and GH secretion (3, 6 4 , we evaluated the responses of autonomic nervous system activity in children with GH deficiency syndromes. SUBJECTS AND METHODSPatients in this study were referred for evaluation of short stature. None of the patients had gastrointestinal or pancreatic disorders at the time of evaluation. All diagnostic procedures were conducted in the Endocrine Diagnostic Unit at the University of Maryland. After an overnight fast, each patient underwent an insulin tolerance test (8) followed by an arginine stimulation test for diagnosis of GH deficiency (8). During insulin-induced hypoglycemia blood glucose levels were followed in real time using a continuous glucose monitor (9, 10). Blood samples for GH, PP, E, NE, and cortisol were drawn at baseline at 20 min, at glucose nadir identified in real time, and at 10 and 20 min af...