Blunted prolactin response to hypoglycemia in patients with hypothalamic-pituitary disease and in subjects receiving estrogen

Abstract

The prolactin response to hypoglycemia was evaluated in 22 control subjects and 8 patients with hypothalamic-pituitary disease but normal basal serum prolactin levels. Eighteen of the 22 control subjects demonstrated at least a twofold prolactin rise in response to hypoglycemia. In contrast to the control subjects, none of the 8 patients demon-strated a prolactin response to hypoglycemia. This blunted prolactin response to hypoglycemia was the only endocrine abnormality in 3 of these 8 patients. In an attempt to better determine the sensitivity of the prolactin response to hypoglycemia as an index of early pituitary disease, the effect of a short course of estrogen on the prolactin response to hypoglycemia was examined. Estrogen was selected because of its known acute stimulatory effect on pituitary mitosis and chronic effects that lead to pituitary tumor formation in rodents. Accordingly, diethylstilbestrol (DES) 5 mg t.i.d. was administered orally to 6 normal men for 3 days, a period known to stimulate pituitary mitotic activity in rodents. Diethylstilbestrol treatment caused significant elevation of the baseline prolactin (8 ± 2 versus 18 ± 3 ng/ml, p < 0.05); however, the prolactin response to hypoglycemia was blunted (8 ± 2–30 ± 10 ng/ml, p < 0.05, before DES; 18 ± 3–20 ± 5 ng/ml after DES, p > 0.05). This estrogen-induced blunted prolactin response to hypoglycemia resembled the blunted prolactin response to hypoglycemia found in patients with hypothalamic-pituitary disease.