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

Anna Stroud*, Pearl Dhaliwal, Raquel Alvarado, Mark J. Winder, Benjamin P. Jonker, Jessica W. Grayson, Aneeza Hamizan, Richard J. Harvey, Ann McCormack

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)


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- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 μg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 μg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, 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 μg/dL (< 55 nmol/L).

Original languageEnglish
Pages (from-to)595-609
Number of pages15
Issue number5
Early online date20 Jul 2020
Publication statusPublished - Oct 2020


  • ACTH-secreting pituitary adenoma
  • Cushing disease
  • Pituitary neoplasms
  • Transsphenoidal surgery

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