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Effect of Central Nervous System Dopaminergic Activation on Prolactin Secretion in Man: Evidence for a Common Central Defect in Hyperprolactinemic Patients with and without Radiological Signs of Pituitary Tumors^*

Department of Obstetrics and Gynecology, University of Milan, the Second Department of Medicine, Fatebenefratelli Hospital, and the Biostatistical Unit, Mario Negri Institut for Pharmacological Research Milan, Italy

Address requests for reprints to: Dr. P. G. Crosignani, Clinica Ostetrica e Ginecologia IV, Facolta di Medicina, Universita Degli Studi di Milano, Via M. Mellon, 52, Milano 20129, Italy.

Previously, it has been shown that the PRLsuppressive effect of L-dopa is unchanged by carbidopa pretreatment in healthy subjects but is markedly impaired in patients with PRL-secreting tumors, suggesting that the inhibitory action of L-dopa is mediated through the central nervous system (CNS) in normal humans and peripherally in patients with prolactinomas. Also, it has been claimed that the administration of nomifensine, a drug which stimulates CNS but not pituitary dopamine receptors, inhibits PRL secretion in hyperprolactinemic patients without, but not with, evidence of pituitary tumors. To further evaluate the possible diagnostic applications of these tests, Ldopa (500 mg) alone and 100 mg plus 35 mg carbidopa after carbidopa pretreatment (50 mg every 6 h) or nomifensine (200 mg) were administered orally to healthy subjects and patients with hyperprolactinemia of different etiology. The mean serum PRL concentration was similarly inhibited in normal subjects by L-dopa alone and by carbidopa plus L-dopa (mean nadir levels, 33.6 ± 2.5% and 31.7 ± 2.8% of basal, respectively; n = 16), while in hyperprolactinemic patients, L-dopa alone was significantly more effective than the combined treatment in both patients with and without radiological evidence of pituitary tumors [n = 20 for each group; mean nadir of serum PRL levels, 32.5 ± 3.9% and 60.1 ± 4.7%, respectively in the tumor group (P < 0.01) and 35.5 ± 3.2% and 60.8 ± 5.1% in patients with normal sella turcicas (P < 0.01)]. Nomifensine administration significantly lowered serum PRL levels only in healthy subjects (mean nadir, 58.9 ± 4.7% n = 19; P < 0.01), while slight decreases occurred in both hyperprolactinemic patient groups. Impaired PRL inhibitory responses to carbidopa plus L-dopa and to nomifensine were also observed in some hyperprolactinemic patients with hypothalamic tumors.

The present results show that none of these tests may be used in the differential diagnosis of hyperprolactinemic states and provide evidence for the existence of a common defect in CNS dopaminergic inhibition of PRL secretion in hyperprolactinemic patients with and without radiological signs of pituitary tumors as well as in patients with hypothalamo-pituitary disconnection. These findings suggest that subjects with hyperprolactinemia of unknown etiology may harbor a pituitary microadenoma too small to be radiologically detected.

^* This work was supported in part by CNR Reproductive Biology and Control of Neoplastic Growth Programs.

Received April 14, 1980.