High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma

Abstract

Objective: This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n = 11) to those in whom a pituitary ACTH adenoma was documented (n = 11).

Design: The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH-secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed.

Measurements: Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24-hour free urinary cortisol with no suppression in response to low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH-GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery.

Results: Similar results were observed in patients with and without ACTH-secreting adenomas regarding cure rate, and free urinary cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma cortisol levels in cured patients were lower in subjects with ACTH-secreting adenomas than in those without pituitary tumours (P < 0.05). Areas under the curve of PRL (P < 0.002) and LH (P < 0.04) were significantly higher in patients without pituitary adenoma after TRH-GnRH administration. Compared to controls, the peak prolactin level after TRH-GnRH administration was higher in patients without pituitary adenoma (P < 0.005) and lower in those with ACTH adenoma (P < 0.005). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH-GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P < 0.001), while the CT-scan findings were suggestive of pituitary adenoma in six patients of each group.

Conclusion: This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH-secreting adenomas by their high prolactin levels after TRH-GnRH administration.