Treatment of pituitary-dependent Cushing's syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery

BACKGROUND The preferred treatment of Cushing's disease (CD) nowadays is tr anssphenoidal pituitary surgery (TPS). Prior to TPS, patients at the Leiden University Medical Centre were treated by unilateral adrenalectomy followe d by external pituitary irradiation (UAPI). We report on long-term results of both UAPI and TPS and compare remission, relapse rates, and complication s. PATIENTS AND METHODS A retrospective study was carried out on 130 patients with CD. Patients with pituitary macroadenoma were excluded. Eighty-six and 44 patients underwent UAPI and TPS, respectively. Of these patients, 85 an d 41 were evaluable for long-term results. RESULTS Remission following UAPI and TPS was identical at 64% (54/85 and 27 /41). Cumulative relapse was also comparable - 17% (9/54) and 22% (6/27), r espectively, - for UAPI and TPS, although the mean follow-up periods were d ifferent - 21.4 years and 8.5 years, respectively. Cumulative disease-free survival curves after UAPI and TPS are identical until 5 years of follow-up , but diverge thereafter indicating more sustained remissions following UAP I (P = 0.17, Wilcoxon statistic). Pituitary dysfunction following UAPI (36% ) and pituitary surgery (55%) likewise did not differ significantly. Howeve r, pituitary dysfunction was an immediate event after TPS, whereas it devel oped after a mean interval of 17.8 years following UAPI. Low-dose dexamethasone testing during follow-up had no value in predicting therapeutic outcome. CONCLUSIONS The results of unilateral adrenalectomy followed by external pi tuitary irradiation do not justify that this therapy is totally abandoned i n favour of transsphenoidal pituitary surgery. Unilateral adrenalectomy fol lowed by external pituitary irradiation is a valid therapeutic modality for the treatment of Cushing's disease, and could be considered as alternative to bilateral adrenalectomy and under some circumstances to transsphenoidal pituitary surgery.