Absence of nocturnal elevation of plasma prolactin concentrations in Cushing's disease

The mean prolactin concentration during sleep and the per cent change (increase) and increment in the nocturnal elevation of plasma prolactin concentrations were significantly reduced (P less than .01, less than .01, and less than .001, respectively) in 6 untreated patients with clinically active Cushing's disease, compared with concentrations seen in normal subjects. There was no significant difference between mean-awake and mean-sleep plasma prolactin concentration in these patients, in contrast to that seen in normal subjects. In contrast, patients with hypercorticism secondary to adrenal adenoma (n = 2) or receiving long-term, high-dose corticosteroid therapy (n = 6) did not differ significantly from normal subjects in the percentage change seen in the nocturnal elevation of their plasma prolactin concentrations. Although mean prolactin concentration during sleep was reduced in these two categories of hypercorticism, a significant difference was still present between mean-awake and mean-sleep plasma prolactin concentration. (The nocturnal increment in plasma prolactin concentrations in these patients with hypercorticism compared with that of normal subjects was reduced, P less than .02). The difference between the percentage change and nocturnal increment observed in patients with Cushing's disease versus that seen in these two categories of hypercorticism was significant at P less than .02 and P less than .01, respectively. Four untreated patients with localized hypothalamic tumors also showed a significant reduction in the percentage change and increment in the nocturnal elevation of plasma prolactin concentrations (P less than .05 and P less than .02). In contrast to these findings, the prolactin responses to thyrotropin-releasing hormone (indicative of pituitary responsiveness) in patients with Cushing's disease, patients with adrenal adenoma, or those receiving chronic corticosteroid therapy, were all within the normal range seen in sex-matched control subjects. These findings provide additional evidence for the suggestion that there is altered hypothalamic function in patients with Cushing's disease.