EARLY REPEAT SURGERY FOR PERSISTENT CUSHINGS-DISEASE

The potential efficacy of early repeat transsphenoidal surgery for per sistent Cushing's disease has not previously been examined. On 222 pat ients with no prior pituitary treatment and a preoperative diagnosis o f Cushing's disease, 29 (13%) remained hypercortisolemic after an init ial transsphenoidal pituitary exploration. Seventeen of these 29 patie nts underwent further surgery 7 to 46 days after the initial transsphe noidal approach in order to completely excise suspected residual tumor . Patients were followed for 4 to 84 months (mean +/- standard deviati on, 34 +/- 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 mu g/day was cons idered evidence of recurrence). Of the 17 patients with repeat surgery , 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 mu g/dl); however, in three of these 12, hypercortisolism r ecurred 5, 12, and 24 months later. In 14 patients a lesion that appea red to be a tumor was identified during the initial procedure or on hi stological examination. Of these, 12 had immediate resolution of hyper cortisolism and nine are still in remission. Three patients, in whom n o adenoma could be identified during the initial surgery or an examina tion of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (4 1%) of the 17 patients developed hypopituitarism requiring treatment w ith thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomograp hy or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 pa tients), and the failure of these 17 patients to respond to the initia l transsphenoidal surgery suggest that they may comprise a subset of p atients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, sinc e the alternative treatments (such as radiation therapy, long-term dru g therapy, or bilateral adrenalectomy) also have potential adverse eff ects, early reoperation deserves consideration for the management of p ersistent Cushing's disease, especially when an adrenocorticotrophic h ormone-secreting adenoma was partially excised during the first surger y.