Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis

Purpose Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. Methods Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded. Results The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro-vmacroadenomas (83%v68%,p < 0.01), imaging-visible adenomas (81%v69%,p < 0.01), adenomas confirmed on histopathology (87%v45%,p < 0.01), absence of cavernous sinus invasion (80%v30%,p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 mu g/dL (< 55 nmol/L; 95%v46%,p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmolv1726 nmol,p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 mu g/dL (< 55 nmol/L; 100%v38%,p < 0.01) and operations for recurrencevpersistence (80%v54%,p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. Conclusions TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 mu g/dL (< 55 nmol/L).