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

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.