Clinical review: The strategy of immediate reoperation for transsphenoidal surgery for Cushing's disease

Context: Transsphenoidal surgery is currently the primary therapeutic option for Cushing's disease. Despite considerable initial success, 10-30% of patients fail to achieve lasting remission. Evidence Acquisition: We evaluated a strategy of immediate reoperation in surgical failures judged by plasma cortisol levels that did not fall to 2 mu g/dl or less within 72 h of surgery. Of 215 patients with presumed ACTH microadenomas, treated between 1993 and 2004, 12 met inclusion criteria and had prompt (within 15 d) reoperation for residual or missed ACTH microadenoma. These 12 patients represent 28% of those who did not have evidence of postoperative adrenal insufficiency. Evidence Synthesis: Based on an outcome measure of sustained subnormal or normal plasma cortisol levels, eight of 12 patients (67%) achieved remission from the two operations. Adjunctive therapies (radiotherapy, gamma knife radiosurgery, and adrenalectomy) led to remission in another three patients. It is recognized that this outcome required either total hypophysectomy (one patient) or postoperative hypopituitarism (all patients in remission). Conclusion: Magnetic resonance imaging was not usually helpful in determining therapeutic strategies; however, inferior petrosal sinus sampling was critical in providing confidence that the disease was of pituitary origin. A treatment algorithm is recommended, based on this study.