Hyperprolactinemia in Cushing's disease and Nelson's syndrome

In an attempt to clarify the pathogenesis of hyperprolactinemia associated with Cushing's disease, PRL secretion was evaluated in 42 patients with hyperadrenocorticism (Cushing's disease, 26; and adrenocortical adenoma, 16) and in 10 patients with Nelson's syndrome. Mild hyperprolactinemia was found in 6 patients with Cushing's disease (23%) and in 5 patients with Nelson's syndrome (50%). In contrast, basal plasma levels of PRL were normal in all of the patients with Cushing's syndrome secondary to adrenocortical adenoma. Injection of TRH unequivocally induced PRL release; however, the responses were blunted in patients with Cushing's disease and in those with Nelson's syndrome who had hyperprolactinemia. Short term administration of dexamethasone, on the other hand, failed to alter PRL secretion in these patients. In 5 patients with Cushing's disease, plasma levels of PRL were reevaluated when they developed a typical clinical picture of Nelson's syndrome after bilateral adrenalectomy. Four patients had a definite increase in PRL levels. Immunohistochemistry of pituitary adenomas surgically removed from 7 patients with Cushing's disease or Nelson's syndrome demonstrated, in 4 of them, the presence of PRL-containing cells as well as ACTH-containing cells. Two of these patients had hyperprolactinemia, which was corrected by the removal of pituitary tumors. These results suggest that hyperprolactinemia is not a fortuitous occurrence in patients with Cushing's disease and could be explained by the concomitant production and secretion of PRL from corticotroph adenomas.