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Neonates with Symptomatic Hyperinsulinemic Hypoglycemia Generate Inappropriately Low Serum Cortisol Counterregulatory Hormonal Responses

London Center for Pediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom WC1N 3JH; and Institute of Child Health University College, London, United Kingdom WC1N 1EH

Address all correspondence and requests for reprints to: Dr. K. Hussain, Department of Biochemistry, Endocrinology, and Metabolism, Institute of Child Health, University College London, 30 Guilford Street, London, United Kingdom WC1N 1EH. E-mail: k.hussain{at}ich.ucl.ac.uk.

Serum cortisol plays an important role in counterregulation to hypoglycemia. It antagonizes the peripheral effects of insulin and also directly influences glucose metabolism. Classically serum cortisol concentrations rise in response to hypoglycemia, but the response in neonates with hyperinsulinemic hypoglycemia is unclear. To investigate the serum cortisol responses in neonates with hyperinsulinemic hypoglycemia, 13 neonates (34–40 wk gestation; male/female ratio, 7/6) with hyperinsulinemic hypoglycemia underwent diagnostic fasts. The serum cortisol concentration was measured before the commencement of the fast and at the time of hyperinsulinemic hypoglycemia. The hypoglycemia was then treated with iv glucose (1 ml/kg bolus of 10% dextrose), and serum cortisol concentrations were measured at 10-min intervals for a total of 50 min. Six of the 13 neonates had plasma ACTH concentrations measured at the time of hypoglycemia and then received a 62.5-µg iv bolus injection of Synacthen. The mean (±SEM) serum cortisol concentration 15 min before the hypoglycemic episode was 156 ± 24 nmol/liter, and that at the time of hypoglycemia was 182 ± 28 nmol/liter. Mean cortisol concentrations at 10, 20, 30, 40, and 50 min for the first seven neonates who were not given Synacthen at the time of hypoglycemia were 213 ± 44, 223 ± 48, 209 ± 49, 228 ± 46, and 252 ± 30 nmol/liter, respectively. The six neonates who received an iv bolus dose of Synacthen had significantly greater (P < 0.01) serum cortisol concentrations at the same time points, 208 ± 39, 219 ± 46, 378 ± 139, 664 ± 57, 905 ± 121, 1048 ± 247, and 1192 ± 105 nmol/liter, respectively. Plasma ACTH levels were inappropriately low in all six neonates at the time of hypoglycemia (mean plasma ACTH concentration, 13.2 pg/ml). Neonates with hyperinsulinemic hypoglycemia fail to generate an adequate serum cortisol counterregulatory hormonal response. This appears to be related to the lack of drive from the hypothalamic-pituitary axis, with inappropriately low plasma ACTH concentrations at the time of hypoglycemia. The normal serum cortisol response to an iv bolus injection of Synacthen suggests that this is a centrally mediated phenomenon and does not imply that these patients have adrenal insufficiency.

Some of this work was undertaken by Great Ormond Street Hospital for Children National Health Service Trust, who received a proportion of its funding from the National Health Service Executive. The views expressed in this publication are those of the authors and are not necessarily those of the National Health Service Executive.

Abbreviations: HI, Hyperinsulinism in infancy; LHA, lateral hypothalamic area; VMN, ventromedial nucleus.

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