Counter-Regulatory Hormone Responses to Insulin-Induced Acute Hypoglycemia in Hypopituitary Patients

Abstract

Patients with hypopituitarism are predisposed to fasting hypoglycemia and are considered unusually sensitive to insulin-induced acute hypoglycemia. However, whether impaired response of counter-regulatory hormones, such as glucagon, epinephrine (E), and nor-epinephrine (NE) contribute to the susceptibility to acute hypoglycemia in hypopituitary patients has not been systematically evaluated. Therefore, we compared counter-regulatory hormone responses to insulin-induced acute hypoglycemia in 9 patients with hypopituitarism who were off hormone replacement therapy and 13 normal healthy subjects. All subjects received aa prime-continuous intravenous infusion of insulin (0.1 Unit/kg body weight.h) till plasma glucose declined to less than 2.5 mmol/l or occurrence of hypoglycemic symptoms. All normal subjects and 7 out of 9 hypopituitary patients recovered spontaneously from hypoglycemia. Two hypopituitary patients with hypothalamic pathology however needed intravenous glucose, glucagon and hydrocortisone to assist recovery from hypoglycemia. Overall, patients with hypopituitarism showed a slower rate of recovery of plasma glucose after hypoglycemia than normal subjects (0.78 +/- 0.33 mmol/l.h vs. 1.72 +/- 0.15 mmol/l.h, respectively; p = 0.02). The responses of key counter-regulatory hormones, glucagon, E and NE, to hypoglycemia however were essentially similar in both the groups. We conclude that the lack of cortisol (secondary to ACTH deficiency) and GH in hypopituitary patients may be primarily responsible for the slow recovery of plasma glucose after acute hypoglycemia; and plasma glucagon, E, and NE responses are not impaired.

Impaired Counterregulation of Glucose in a Patient with Hypothalamic Sarcoidosis

“…17 Glucagon and epinephrine have a crucial role in the recovery from insulin-induced hypoglycemia, whereas cortisol and growth hormone are of minor importance. 7,18,19 The normal pattern of glucose recovery that we found in the patients with pituitary insufficiency but presumably normal responses of other counterregulatory hormones 8 further illustrates this concept and points to defective catecholamine and glucagon responses as the factors responsible for the persistent hypoglycemia after intravenous injection of insulin in our patient. Besides stimulating the release of pituitary hormones, the hypoglycemia-mediated activation of hypothalamic centers increases the activity of peripheral cholinergic and sympathetic neurons, which in normal subjects markedly increase the heart rate and muscle sympathetic-nerve activity.…”

Increased insulin sensitivity in young, growth hormone deficient children

“…By inference, growth hormone deficiency (GHD) may be expected to result in increased insulin sensitivity. Young GH deficient children have a tendency to both fasting and readily provoked hypoglycaemia (Hopwood et al ., 1975; Haymond et al ., 1976; Bougneres et al ., 1985), probably resulting from impaired hormonal counter‐regulation (De Feo et al ., 1989; Garg et al ., 1994). Increased insulin sensitivity could also contribute to their hypoglycaemia, however, this has not been directly demonstrated.…”

Risk for severe hypoglycaemia with unawareness in GH‐deficient patients during the insulin tolerance test

“…27 Thus, the nadir of plasma glucose will only last about 5 min, at a mean plasma glucose level just above 2 mmol / l, and will thereafter steadily increase to normal levels. 27 A slow recovery from hypoglycaemia during an ITT has been shown in adults with multiple pituitary deficiencies, 28 and ACTH and GH insufficiency have been suggested as primarily responsible. 28 There was, however, no difference in the duration of hypoglycaemia between the eight patients with or without ACTH insufficiency, which would again favour GH as more important for a quick recovery of insulin-induced hypoglycaemia.…”