Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis

Pituitary. 2021 Oct;24(5):797-809. doi: 10.1007/s11102-021-01158-z. Epub 2021 May 25.


Purpose: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development.

Data sources: Systematic literature search in four databases.

Study selection: Observational studies reporting the prevalence of NS after BA in adult patients with CD.

Data extraction: Data extraction and risk of bias assessment were performed by three independent investigators.

Data synthesis: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)].

Conclusions: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.

Keywords: Bilateral adrenalectomy; Corticotroph adenoma; Cushing’s disease; Nelson’s syndrome.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adrenalectomy
  • Adult
  • Humans
  • Nelson Syndrome* / epidemiology
  • Nelson Syndrome* / surgery
  • Pituitary ACTH Hypersecretion* / epidemiology
  • Pituitary ACTH Hypersecretion* / surgery
  • Pituitary Gland
  • Prevalence