Dynamic Evaluation of Prolactin Secretion with Perphenazine in Normal and Hyperprolactinemic Subjects

Abstract

Precise criteria for normal phenothiazine-induced prolactin responsiveness were established in men and women following oral perphenazine (Trilafon^®) ingestion. Perphenazine was chosen in lieu of the more commonly utilized phenothiazine, chlorpromazine, because of its freedom from major side effects. During 77 studies, the perphenazine test was found to be a safe and simple outpatient procedure. In order to determine whether the perphenazine test would discriminate pituitary tumor associated elevations in serum prolactin from hyperprolactinemia on a functional basis, the dynamic response of serum prolactin to perphenazine observed in normal subjects was compared to that observed in 3 groups of hyperprolactinemic patients. Group I consisted of 11 patients with histologically proven pituitary tumors; Group II of 12 patients with neuro-ophthalmologic and/or radiographic abnormalities consistent with the presence of pituitary tumors; and Group III of 11 patients without evidence of pituitary tumors. Following perphenazine ingestion, normal women demonstrated a significantly greater prolactin response than normal men. The dynamics of the normal perphenazine-induced prolactin response were defined as follows: 1) a maximum increment of prolactin above baseline of 71 ± 7 ng/ml (1 SEM) with a range of 26-154 ng/ml in women and 20 ± 3 ng/ml with a range of 6-37 ng/ml in men; 2) a substantial increase in serum prolactin concentration in each subject by 3 hours following drug ingestion with a mean increment above baseline of 52 ± 7 ng/ml in women and 16 ± 3 ng/ml in men; and 3) sustained elevations in serum prolactin at 4, 5, and 6 hours in women (increments of 67 ± 7, 62 ± 7, and 54 ± 6 ng/ml, respectively) and in men (18 ± 3, 19 ± 3, and 15 ± 2, respectively). Although random fluctuations in serum prolactin concentration were evident in some patients in Group I, none had normal dynamics as defined by our criteria. In Group II, 9 out of 12 patients failed to respond to perphenazine administration and two patients had normal responses. In contrast to the findings in the first two groups, the majority, or 7 of 11 patients, in Group III had normal prolactin dynamics. In 4 the responses were indistinguishable from the tumor groups. We conclude from this study that each patient with a histologically proven pituitary tumor had an abnormal perphenazine-induced prolactin response suggesting that prolactin responsiveness may be impaired in hyperprolactinemic pituitary tumor patients. The majority of patients with presumptive radiographic evidence of pituitary tumors also had abnormal responses; whereas, the majority of subjects without evidence of tumors had normal prolactin responses. Aberrant responses in the minority of patients in each of the latter 2 groups may have resulted from inaccuracies in classifying patients on the basis of sella polytomography. An alternate explanation is that a minority of patients with and without pituitary tumors may have aberrant perphenazineinduced prolactin responses. Long-term follow-up of these 2 groups of patients will be necessary to explore further the possible predictive value of the perphenazine test in identifying pituitary tumor patients.