Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.