Early repeat surgery for persistent Cushing’s disease: indication, approach and results

Persistence of hypercortisolism after transsphenoidal surgery for Cushing’s disease may be caused by residual tumor tissue, primary removal of a non-ACTH secreting, coexisting adenoma, or negative pituitary exploration. Further treatment options include radio- or pharmacotherapy, adrenalectomy, and repeat pituitary surgery. We evaluated our long-term experience with early repeat surgery in Cushing’s disease which, if successful, is the treatment modality with the most rapid effect.

In between 1986 and 2002, 538 patients diagnosed with Cushing’s disease were treated. Sixty-two patients (11.7%) did not experience remission (determined within the first postoperative days prior to substitution), of whom 20 patients (33%) were selected for early re-surgery during the same hospital stay. Selection criteria included suspected residual tumor tissue accessible by surgery (18 patients), or negative exploration despite endocrinological proven pituitary dependency (2 patients). Re-operation was performed prior to scarring, allowing a rapid re-exposure of the pituitary. Re-exploration of the pituitary was performed, the sella was opened allowing the inspection of both sides of the pituitary up to the cavernous sinus. Intraoperatively, direct ACTH measurement from the cavernous sinus as well as cytology was available, since 1997 also intra-tissue ACTH determination.

Sixteen of 20 patients (80%) achieved remission by early repeat surgery, four patients remained hypercortisolemic, of whom one was successfully re-operated three months later. Of the sixteen initially cured patients, one patient experienced recurrence of disease after five years, successfully treated again by surgery. Surgical complications included CSF-fistula in four cases, partial anterior lobe insufficiency in eight cases, permanent diabetes insipidus in three cases.

In selected patients and experienced hands, early repeat surgery offers a significant chance in failed transsphenoidal surgery. Not surprisingly, additional pituitary exploration increases the risk of anterior and posterior lobe insufficiency.