Dopamine infusion studies in patients with pathological hyperprolactinemia: evidence of normal prolactin suppressibility but abnormal dopamine metabolism.

The cause of pathological hyperprolactinemia (PHP) is not known, although it has been postulated that lactotroph refractoriness to dopamine (DA) is an important factor. We, therefore, studied PRL suppressibility in response to iv DA administered in a dose designed to achieve peripheral plasma DA concentrations in the range reported in rat pituitary portal plasma. Nine normal subjects and 14 patients (8 with probable microadenomas and 6 with macroadenomas) with PHP were studied during a 4-h infusion of 0.5 micrograms/kg X min DA. Serum PRL levels decreased in normal subjects to 18 +/- 3% (mean +/- SEM) of initial basal levels, not significantly different from the fall to 22 +/- 2% of basal levels found in patients with PHP. Maximal PRL suppression in patients with probable microadenomas (21 +/- 2%) was not significantly different from that in those with macroadenomas (22.8 +/- 2.0%). Upon cessation of DA infusion, there was a rapid rebound in PRL release, which was significantly greater (P less than 0.05) in patients (155 +/- 15%) than in normal subjects (118 +/- 13%). Plasma DA levels were measured by gas chromatography/mass spectroscopy and were significantly higher (P less than 0.05) in patients than in normal subjects during the infusion. The MCR for DA in normal subjects (12.5 +/- 2.8 liters/kg X h) was significantly greater (P less than 0.005) than that in patients (6.2 +/- 0.5 liters/kg X h). The data show that the release of PRL in patients with PHP is not refractory to physiological concentrations of DA, but that there is an abnormality of peripheral DA metabolism in these patients. We conclude that the development of PHP is unlikely to be due to insensitivity of lactotrophs to endogenous DA and that patients with PHP have a systemic disturbance of DA metabolism.