Risk factors and long-term outcome in pituitary-dependent Cushing's disease

Although transphenoidal pituitary microsurgery has become the treatment of choice in Cushing's disease, other procedures, such as bilateral adrenalectomy and pituitary irradiation, are currently in use in its management. Indeed, no treatment has proven to be fully satisfactory for this condition. The rates of cure and recurrence after pituitary surgery or irradiation and the incidence of Nelson's syndrome after bilateral adrenalectomy are still open issues. A population of 162 patients with pituitary-dependent Cushing's disease was studied at 1 institution and had a follow-up of at least 2 yr after treatment (median, 7 yr). Patients were divided in subgroups according to the type of treatment: transsphenoidal pituitary microsurgery, bilateral adrenalectomy, or pituitary irradiation. Survival analysis was employed to characterize the outcome of treatment in each subgroup. Predictive factors for success of pituitary surgery were also evaluated. The estimated cumulative percentage of patients remaining in remission after successful pituitary surgery (n = 79) was 93.7% after 2 yr, 80.6% after 5 yr, 78.5% after 7 yr, and 74.1% after 10 yr. Of 8 risk factors examined, the following attained statistical significance: age, clinical severity, presence of major depression, pre- and posttreatment urinary cortisol levels, and posttreatment ACTH level. Pituitary surgery was successful in 79 of 103 patients (76.7%). Surgical failure was significantly associated with lack of pituitary adenoma and the clinical severity and presence of major depression. Of patients treated by bilateral adrenalectomy (n = 63), the estimated cumulative percentage remaining free of Nelson's syndrome was 87.1% after 2 yr, 79.3% after 7 yr, and 71.2% after 10 yr. The occurrence of Nelson's syndrome was significantly related to the pretreatment urinary cortisol level and the presence of pituitary adenoma at previous pituitary surgery. After cure by pituitary irradiation (n = 23), the estimated cumulative percentage of patients remaining in remission was 100% after 2 yr, 81.8% after 5 yr, 71.6% after 7 yr, and 65.1% after 10 yr. Previous pituitary surgery, although unsuccessful, appeared to be a protective factor for relapse. The results indicate that relapse after cure by either pituitary surgery or irradiation is a considerable clinical problem that increases over time. Our findings ascribe new importance to the clinical presentation of patients and indicate subgroups that are at high risk for relapse after pituitary surgery or irradiation and for developing Nelson's syndrome after bilateral adrenalectomy.