Symptomatic reactive hypoglycemia during glucose tolerance test in lithium-treated patients

Glucose, insulin, glucagon, and cortisol responses during a five-hour oral glucose tolerance test (GTT) were evaluated in nine patients with bipolar affective disorders who were receiving lithium treatment and in seven control patients with bipolar affective disorders who were not receiving any treatment. Both the lithium-treated and the control patients were in stable mood at the time of GTT. During GTT mean nadir serum glucose of 48 +/- 2 mg/dL in the lithium-treated patients was significantly lower (P less than 0.001) than mean nadir serum glucose of 62 +/- 2 mg/dL observed in the control subjects. Seven of these nine lithium-treated patients, but none of the control patients, experienced hypoglycemic symptoms coinciding with low serum glucose concentration. In response to hypoglycemia, mean serum cortisol significantly rose (P less than 0.01) to 22 +/- 3 micrograms/dL in the lithium-treated patients, whereas mean serum cortisol levels gradually declined to 10 +/- 2 micrograms/dL in the control patients at 300 minutes. Despite symptomatic postglucose hypoglycemia, plasma glucagon levels in the lithium-treated patients were similar to those observed in the control patients. These findings suggest that chronic lithium treatment is associated with a symptomatic and biochemical hypoglycemia during GTT, which is characterized by a rise in serum cortisol but by lack of appropriate rise in plasma glucagon concentrations.