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

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

Eleni Papakokkinou  1   2 , Marta Piasecka  1   2 , Hanne Krage Carlsen  3 , Dimitrios Chantzichristos  1   2 , Daniel S Olsson  1   2 , Per Dahlqvist  4 , Maria Petersson  5   6 , Katarina Berinder  5   6 , Sophie Bensing  5   6 , Charlotte Höybye  5   6 , Britt Edén Engström  7 , Pia Burman  8 , Cecilia Follin  9 , David Petranek  9 , Eva Marie Erfurth  9 , Jeanette Wahlberg  10   11 , Bertil Ekman  10 , Anna-Karin Åkerman  11 , Erik Schwarcz  11 , Gudmundur Johannsson  1   2 , Henrik Falhammar  5   6 , Oskar Ragnarsson  12   13
Affiliations
Meta-Analysis

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

Eleni Papakokkinou et al. Pituitary. 2021 Oct.

Abstract

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.

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Flowchart of study selection
Fig. 2
Fig. 2
Forest plot showing individual studies and pooled prevalence of Nelson’s syndrome after bilateral adrenalectomy in patients with Cushing’s disease. *Additional data
Fig. 3
Fig. 3
Forest plot showing individual studies using magnetic resonance imaging and pooled prevalence of Nelson’s syndrome after bilateral adrenalectomy in patients with Cushing’s disease
Fig. 4
Fig. 4
Forest plot showing the RR (relative risk) and 95% CI for Nelson’s syndrome in patients treated with radiotherapy prior to bilateral adrenalectomy versus no radiotherapy. RR could not be calculated when there were no cases in the RTX or no RTX arms, and when no events in either arm. *Additional data. RTX, radiotherapy prior to bilateral adrenalectomy or prophylactic radiotherapy
Fig. 5
Fig. 5
Forest plot showing the RR (relative risk) and 95% CI for Nelson’s syndrome in patients treated with pituitary surgery prior to bilateral adrenalectomy versus no pituitary surgery. RR could not be calculated when there were no cases in the surgery or no surgery arms, and when no events in either arm. *additional data. Abbreviations: Surgery, pituitary surgery prior to bilateral adrenalectomy
Fig. 6
Fig. 6
Bubble plot showing the influence of age at BA on the prevalence of Nelson’s syndrome. The bubble sizes are proportional to the weight of the studies in the meta-analysis. Coefficient estimate (β) and p value for the effect of age at BA are indicated by the regression line
See this image and copyright information in PMC

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