Sympathoadrenal counterregulation in patients with hypothalamic craniopharyngioma

In humans, the role of hypothalamic centers for activation of counterregulatory release of catecholamines and glucagon during hypoglycemia is unclear. To address this question, we investigated the counterregulatory response to acute insulin-induced hypoglycemia of glucagon, epinephrine, and norepinephrine in eight patients who had undergone transcranial surgery for a craniopharyngioma extending to the hypothalamic region. We compared the patients' responses with those of four patients suffering from hypopituitarism and of six healthy subjects. After the i.v. injection of 0.1 U of human insulin per kg of body weight in the patients or 0.15 U in healthy subjects, the plasma glucose concentrations decreased to similar minimum levels within 30 min in all three groups. All subjects recovered spontaneously from hypoglycemia within 2 h. In five of eight craniopharyngioma patients, only a small counterregulatory rise in plasma epinephrine (< or =2-fold) and norepinephrine could be observed (P < 0.05 for epinephrine and P = 0.22 for norepinephrine vs. healthy controls). During hypoglycemia, virtually no adrenergic symptoms (tremor, heart pounding, and anxiety) were reported by these five patients, and changes in the heart rate were diminished. In three craniopharyngioma patients, the counterregulatory increase in catecholamines was unimpaired, adrenergic symptoms were reported and a rise in heart rate was observed during hypoglycemia. In all craniopharyngioma patients, the counterregulatory glucagon response to hypoglycemia was preserved and orthostasis increased both catecholamines and the heart rate similar to in the patients with hypopituitarism as well as in the healthy controls. Our results demonstrate selective impairment of counterregulatory sympathoadrenal activation in patients who had undergone surgery for a craniopharyngioma extending to the hypothalamic region. This strongly suggests the involvement of hypothalamic centers in hypoglycemia-induced activation of the sympathoadrenal axis in humans. It remains unclear as to whether hypoglycemia-induced glucagon secretion is also controlled by the hypothalamus. However, a common hypothalamic center controlling both counterregulatory catecholamine and glucagon release is unlikely, and sympathoadrenal activation is not required for hypoglycemia-induced glucagon secretion in humans.