Hyperprolactinemia in Cushing's disease
Bruno, O.D.; Pinkas, M.; Rossi, M.A.
Medicina 45(1): 5-10
1985
ISSN/ISBN: 0025-7680 PMID: 2851694 Document Number: 259957
Several authors have reported changes in prolactin secretion in diseases of the hypothalamic-hypophyseal-adrenal axis. In normal subjects, the administration of glucocorticoids can acutely diminish the prolactin response to hypoglycemia. Hyperprolactinemia and its correlation with plasma ACTH has been described in Nelson's syndrome. Similarly, high prolactin levels have been observed in Cushing's disease and, in the latter, an association with the amenorrhea-galactorrhea syndrome has been reported. However, other investigators have found normal basal serum prolactin and the absence of its normal nocturnal increase in patients with Cushing's disease. We investigated the immunoreactive basal plasma ACTH and the basal and TRH-stimulated serum prolactin levels in 23 women with Cushing's disease (Table 1); the relationship between prolactin levels and the presence of pituitary tumors was also investigated. Basal plasma ACTH concentrations ranged from 28 to 478 pg/ml. Of the 23 patients, 14 (60.8%) had elevated PRL levels (over 24 ng/ml). Prolactin increases were moderate (25 to 76 ng/ml) in all but one patient (600 ng/ml) (Fig. 1). No significant correlation between PRL and ACTH concentration was found. In 17 of the 23 patients, a pituitary adenoma was found at surgery (15 cases) or autopsy (2 cases): of the 17, 10 were hyperprolactinemic. PRL responses to intravenous TRH were evaluated in 7 patients with normal or slightly raised basal levels: two of them showed hyperresponsiveness to TRH whereas the remaining behaved normally (Fig.2). No relationship could be found between basal PRL level and response to TRH and the presence or type of pituitary tumors. The administration of the dopamine agonist, bromocryptine, to one of the hyperprolactinemic patients with amenorrhea resulted in resumption of cyclic vaginal bleeding in spite of unchanged hypercortisolism; her prolactin values changed from 29 ng/ml before treatment to 7 ng/ml under bromocryptine, just prior to the successful removal of a small pituitary adenoma (Fig.3). Some hypotheses can be proposed to explain the occurrence of hyperprolactinemia in Cushing's disease. First, the role of hypercortisolism seems unlikely in view of the known effects of glucocorticoids on prolactin secretion in normals and of the persistence of hyperprolactinemia after total adrenalectomy for Cushing's disease (Nelson's syndrome). Secondly, one must consider the hypothetical role that .beta.-endorphin, which is an habitual companion of ACTH release, may have in stimulating PRL release since such an action has been demonstrated in in vitro studies. Thirdly, a primitive dopamine depletion of the hypothalamus could be the cause of prolactin stimulation; the demonstration of neural tissue in intermediate lobe adenomas in some patients with Cushing's disease, hyperprolactinemia and significant suppression of ACTH secretion by bromocryptine seem to militate in this sense. Finally, a most probably mechanism could be the direct secretion of prolactin by a mixed adenoma. Indeed, the prevalence of hyperprolactinemia in the present series is similar to that reported for acromegaly and for the so-called "functionless" chromophobe adenoma. In addition, the simultaneous production of ACTH and PRL by two different cellular lines in a case of Cushing's disease with hyperprolactinemia has recently been reported. Whatever the mechanism, the finding of high PRL levels during the evaluation of a patient with Cushing's syndrome is suggestive of a pituitary origin. The elevated PRL concentrations might also be partially responsible for the severe menstrual alterations currently seen in Cushing's disease.