Ectopic ACTH-secreting pituitary adenomas

The diagnosis of Cushing's disease (CD) is based on several endocrinological parameters, with no single test being specific. In a certain amount of patients MRI fails to detect a pituitary tumor. Extensive pituitary exploration may be necessary. Sometimes hypophysectomy is advocated, ignoring the possibility of ectopic pituitary adenoma.

Out of 70 patients undergoing transsphenoidal surgery for ACTH-secreting pituitary adenomas, four (6%) presented with primarily ectopic adenomas (2 primary operations, 2 reoperations; 3 with CD, one with Nelson's syndrome).

Patient 1 (female, 32 ys) underwent negative pituitary exploration for CD elsewhere without remission. After reoperation with excision of a purely intracavernous microadenoma and subsequent remission, recurrence of hypercortisolism occurred after 14 months. Sellar MRI was negative, bilateral adrenalectomy (blAdx) was performed. Patient 2 (female, 36 ys) with CD and negative MRI was primarily operated on a 5 mm microadenoma located outside the sellar compartment in the left cavernous sinus using intraoperative ultrasound. Long term remission of hypercortisolism was achieved. Patient 3 (female, 34 ys) had undergone extensive negative pituitary exploration for CD elsewhere 13 years before, and underwent subsequent blAdx. After 9 years transsphenoidal surgery for an exclusively left parasellar infiltrative macroadenoma was performed. ACTH declined from > 800 pg/ml to < 80 pg/ml. No tumor remnant was visible in MRI. Case 4 (female, 38 ys) with endocrinological proven CD underwent (negative) pituitary exploration with removal of a small mucosal tumor at the septum of the sphenoid sinus during transsphenoidal approach. This turned out to be an ACTH-secreting adenoma. Remission of hypercortisolism occurred.

In cases with negative pituitary exploration, the possilibity of ectopic ACTH-secreting adenoma should be taken into account. Hypophysectomy should be avoided in primary operations.