Detection of recurrent Cushing's disease: proposal for standardized patient monitoring following transsphenoidal surgery

Transsphenoidal surgery (TSS) is first-line treatment for Cushing's disease (CD), a devastating disorder of hypercortisolism resulting from overproduction of adrenocorticotropic hormone by a pituitary adenoma. Surgical success rates vary widely and disease may recur years after remission is achieved. Recognizing CD recurrence can be challenging; although there is general acceptance among endocrinologists that patients need lifelong follow-up, there are currently no standardized monitoring guidelines. To begin addressing this need we created a novel, systematic algorithm by integrating information from literature on relapse rates in surgically-treated CD patients and our own clinical experiences. Reported recurrence rates range from 3 to 47 % (mean time to recurrence 16-49 months), emphasizing the need for careful post-surgical patient monitoring. We recommend that patients with post-operative serum cortisol < 2 A mu g/dL (measured 2-3 days post-surgery) be monitored semiannually for 3 years and annually thereafter. Patients with post-operative cortisol between 2 and 5 A mu g/dL may experience persistent or subclinical CD and should be evaluated every 2-3 months until biochemical control is achieved or additional treatment is initiated. Post-operative cortisol > 5 A mu g/dL often signifies persistent disease and second-line treatment (e.g., immediate repeat pituitary surgery, radiotherapy, and/or medical therapy) may be considered. This follow-up algorithm aims to (a) enable early diagnosis and treatment of recurrent CD, thereby minimizing the detrimental effects of hypercortisolism, and (b) begin addressing the need for standardized guidelines for vigilant monitoring of CD patients treated by TSS, as demonstrated by the reported rates of recurrence.