RECURRENT HYPOGLYCEMIA DOES NOT IMPAIR THE CORTISOL RESPONSE TO ADRENOCORTICOTROPIN INFUSION IN HEALTHY HUMANS

Previous studies have shown that hypoglycemia may reduce counterregula tory responses to subsequent hypoglycemia in healthy subjects and in p atients with diabetes. The effect of hypoglycemia on the hormonal resp onse to a nonhypoglycemic stimulus is uncertain. To test the hypothesi s that the cortisol response to corticotropin (ACTH) infusion is indep endent of antecedent hypoglycemia, 10 healthy subjects received a stan dard ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] int ravenously over 240 minutes) at 8:00 AM on day 1 and day 3 and a hypog lycemic insulin clamp study (1 mU/kg/min) at 8:00 AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L to 2. 8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03 an d 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects als o had paired control studies in random order during which a 330-minute euglycemic clamp (mean glucose, 5.0 +/- 0.11 mmol/L) instead of a hyp oglycemic clamp was performed on day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol (435 +/- 46 v 317 +/- 40 n mol/L, P < .02) both decreased from day 1 to day 3 following interveni ng hypoglycemia. In contrast, with intervening euglycemia, neither bas al ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/- 38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC) for the cortisol response to successive ACTH infusions was incre ased (4,734 +/- 428 nmol/L over 240 minutes [day 3] v 3,526 +/- 434 nm ol/L over 240 minutes [day 1], P < .01). The maximum incremental corti sol response was also significantly increased (805 +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with interval euglycem ia (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3.709 +/- 391 nmol /L over 240 minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3] v 592 +/- 85 nmol/L [day 1] were unchanged. Fol lowing exposure to intermittent hypoglycemia in healthy humans, fastin g morning ACTH and cortisol levels are reduced and the incremental cor tisol response to an infusion of ACTH is enhanced. The enhanced cortis ol response to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal gl and by endogenous ACTH produced during the hypoglycemia. These data su ggest that adrenal function testing by exogenous ACTH administration i s not impaired by prior exposure to hypoglycemia. Moreover, the reduce d cortisol response to recurrent hypoglycemia in patients with well-co ntrolled diabetes is not likely the result of impaired adrenal respons iveness. Copyright (C) 1998 by W.B. Saunders Company.