The adrenomedullary and glucagon responses of hypopituitary children to insulin-induced hypoglycemia.

Abstract

Summary: The activity of phenyl-N-methyl transferase (PNMT), the adrenomedullary enzyme which catalyzes the N-methylation of norepinephrine (NE) to epinephrine (E) is induced by endogenous glucocorticoid hormones secreted by the adrenal cortex. We quantitated the urinary output of NE and E before, during, and after insulin-induced hypoglycemia in patients with pituitary dysfunction. Plasma concentrations of cortisol, growth hormone, and glucagon were measured simultaneously. The study population was comprised of nine healthy controls (group 1), eight children with growth hormone deficiency (group 2), and eight children with combined growth hormone and cortisol deficiencies (group 3). Recovery from acute hypoglycemia was similar in all groups. Mean plasma glucagon values reached a maximum at 30 min after insulin injection, and no significant differences were observed among the groups. Plasma cortisol levels were similar in groups 1 and 2, maximum values ocurring at 45 min after insulin. Patients in group 3 did not increase their cortisol concentrations above 5.5 μg/d despite a greater than 50% drop in blood glucose. Mean urinary E output of all groups increased significantly above pretest values (groups 1 and 2, P < 0.001; and group 3, P < 0.01), whereas NE levels were unchanged. After hypoglycemia, the mean E increments in the control and cortisol-deficient groups were not significantly different. The data can be interpreted in two ways. Endogenous cortisol production in ACTH-deficient bypopituitary children is sufficient to maintain PNMT activity at a level needed for synthesis of E from NE. Alternatively, cortisol may not be essential for E release during acute hypoglycemia because hypothalamic regulatory mechanisms supervene, and direct neural stimulation promotes PNMT activity and synthesis of E. We conclude that patients with cortisol and growth hormone deficiencies are able to recover from acute hypoglycemia when hepatic glycogen stores are adequate because there is sufficient release of E or because other adrenergic mechanisms stimulate glucagon release and hepatic glycogenolysis. Speculation: Although children with cortisol and growth hormone deficiencies are able to recover from acute hypoglycemia, many do not tolerate a prolonged fast because of diminished gluconeogenesis and depletion of hepatic glycogen.