Long-term follow-up and predictors of recurrence of Cushing's disease

Transsphenoidal surgery is the first-line treatment for Cushing's disease to selectively remove the tumor. The rate of postoperative remission is estimated around 70%-80% in expert centers. However, the long-term remission rate is lower because of recurrence during follow-up that can be observed in 15% to 25% of the patients depending on the studies and duration of follow-up. There is no significant predictive factor of recurrence before surgery, but postoperative corticotroph insufficiency and its duration has been found to be a protective factor for recurrence in many studies. The persistence of a positive response to desmopressin after surgery is associated with a higher rate of recurrence. Long term monitoring for recurrence with annual clinical and hormonal investigations after the hypothalamic-pituitary-adrenal axis postoperative recovery is advised. The biological tests used for the diagnosis of Cushing's syndrome (24 h-urinary-free cortisol [UFC], late-night salivary or serum cortisol, 1 mg dexamethasone suppression test) can be used to screen for recurrence. Several studies report that increased late night cortisol and alterations of dynamic testing can be observed before the increased 24 h-UFC. For this reason it is suggested that late-night salivary cortisol would be a very sensitive tool to diagnose recurrence, pending the realization of several assays in case of borderline or discrepant result. This review will summarize the knowledge about recurrence of Cushing's disease after pituitary surgery and the current recommendations for its monitoring and diagnosis.