Hypoglycemia as a provocative test of prolactin release

Abstract

Insulin-induced hypoglycemia has been traditionally used to test growth hormone (GH) and cortisol reserve. In order to determine its usefulness as a provocative test for prolactin (PRL) release, 31 healthy men and women, 38 patients with definite pituitary abnormalities (pituitary tumors, 17; hypopituitarism [other causes]—complete, 4, or partial, 17), and 17 patients with suspected pituitary dysfunction (delayed puberty, 5; short stature, 4; secondary amenorrhea, 6; empty sella, 2, received regular i.v. insulin (0.05–0.15 U/kg), and the plasma was assayed serially for PRL, GH, cortisol, and glucose. In the 31 healthy subjects, PRL increased from 16.3 ± 1.8 ng/ml (mean ± SEM) to 45.5 ± 7.9 ( p < 0.001) at 60 min and was still elevated at 120 min (25.8 ± 3.1 ng/ml). The maximal rise to 52.2 ± 8.0 ng/ml occurred between 40 and 90 min. There was no significant sex difference in the maximal PRL increase, maximal increment, or concentration at any time. In 21 of the 31 subjects, PRL increased at least 10 ng/ml with a doubling of baseline levels—criteria for a positive response. In addition, 12 of the healthy subjects received thyrotropin-releasing hormone (TRH) (500 μg i.v.) while 5 received chlorpromazine (50 mg i.m.). There was no significant difference among the maximal prolactin increments following insulin (36.7 ± 7.9 ng/ml), TRH (46.4 ± 6.3 ng/ml), or chlorpromazine (63.4 ± 21.9 ng/ml). In patients with definite pituitary abnormalities, 28 of 38 had diminished PRL release after insulin. Of these 28, 23 also had inadequate GH and 13 impaired cortisol release. In the 10 partially hypopituitary subjects with normal PRL responses, GH increased normally in 7 and cortisol in all. Thirteen of the 17 patients with suspected pituitary dysfunction had adequate PRL increases, while the GH and cortisol responses were intact in 16 and 17 subjects, respectively. Overall, the PRL response was concordant with changes in GH in 44 of 55 patients and in cortisol in 32 of 55 patients. It is concluded that insulin-induced hypoglycemia (1) releases PRL in most normal subjects and (2) is useful in determining the integrity of the hypothalamic pituitary axis for PRL release in patients with suspected abnormalities of pituitary function. Moreover, in combination with TRH, it may aid in localizing the site of abnormality in patients with these disorders.