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

Pia Burman, Oskar Ragnarsson, Henrik Falhammar, Gudmundur Johannsson, Erik Schwarcz, Anna-Karin Åkerman, Bertil Ekman, Jeanette Wahlberg, Eva Marie Erfurth, David Petranek, Cecilia Follin, Eleni Papakokkinou, Britt Edén Engström, Charlotte Höybye, Sophie Bensing, Katarina Berinder, Maria Petersson, Per Dahlqvist, Daniel S Olsson, Dimitrios Chantzichristos, Hanne Krage Carlsen, Marta Piasecka

Journal: Pituitary 2022;24(5):797-809

PMID: 34036460

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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 (I 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.

Address: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.; The Department of Endocrinology, Sahlgrenska University Hospital, Blå stråket 5, 413 45, Gothenburg, Sweden.; Department of Environmental and Occupational Health School of Public Health and Community Medicine, University of Gothenburg, 4053, Gothenburg, Sweden.; Department of Public Health and Clinical Medicine, Umeå University, 901 87, Umeå, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden.; Department of Endocrinology, Karolinska University Hospital, 171 76, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Uppsala University Hospital, and Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, 751 85, Uppsala, Sweden.; Department of Endocrinology, Skåne University Hospital, University of Lund, 205 02, Malmö, Sweden.; Department of Endocrinology, Skåne University Hospital, 222 42, Lund, Sweden.; Department of Endocrinology and Department of Medical and Health Sciences, Linköping University, 581 83, Linköping, Sweden.; Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, 702 81, Örebro, SE, Sweden.; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden. [email protected].; The Department of Endocrinology, Sahlgrenska University Hospital, Blå stråket 5, 413 45, Gothenburg, Sweden. [email protected].

DOI: 10.1007/s11102-021-01158-z