Objective: To attempt to establish a reference range of glucagon concentrations during hypoglycemia.
Methods: We measured glucagon, cortisol, and growth hormone responses in 65 patients with insulinoma and 29 normal control subjects who underwent a 72-hour fast. For comparison, we also assessed these responses in eight patients with noninsulinoma pancreatogenous hypoglycemia syndrome.
Results: At the end of the fasts, median serum cortisol (19.0 mg/dL [range, 3.7 to 44.0] versus 11.0 mg/dL [range, 5.0 to 28.0], respectively; P<0.001) and growth hormone levels (3.5 ng/mL [range, 0.1 to 46.0] versus 1.2 ng/mL [range, 0.1 to 34.0], respectively; P = 0.021) were higher, whereas plasma glucagon (54.5 pg/mL [range, 11.0 to 170.0] versus 75.0 pg/mL [range, 17.0 to 940.0], respectively; P = 0.012) was lower in patients with insulinoma (serum glucose level, 39 mg/dL [range, 14 to 58]) than in control subjects (serum glucose level, 63 mg/dL [range, 47 to 89]). In contrast, the 8 patients with noninsulinoma pancreatogenous hypoglycemia syndrome, a disorder of postprandial hyperinsulinemic hypoglycemia with normal findings on a 72-hour fast (serum glucose level, 71.5 mg/dL [range, 48 to 82]), had concentrations of glucagon (81.0 pg/mL [range, 47.0 to 150.0]), cortisol (10.5 mg/dL [range, 2.7 to 17.0]), and growth hormone (1.5 ng/mL [range, 0.8 to 6.9]) similar to those in the control subjects. On multivariate analysis, the duration of the fast, baseline glucagon concentration, and male gender (but not age, body mass index, or concentrations of glucose and insulin) were correlated with end-of-fast glucagon concentration.
Conclusion: Defective glucagon secretion in hypoglycemic disorders applies to the stimulus of hypoglycemia but not to food deprivation. A conservative estimate for glucagon deficiency based on the minimal observed glucagon response could be a level of 10 pg/mL during hypoglycemia.