Surveillance Improves Outcomes for Carriers of SDHB Pathogenic Variants: A Multicenter Study

• Published in: The journal of clinical endocrinology and metabolism 2022-04, Vol.107 (5), p.e1907-e1916
• Main Authors: Davidoff, Dahlia F, Benn, Diana E, Field, Michael, Crook, Ashley, Robinson, Bruce G, Tucker, Katherine, De Abreu Lourenco, Richard, Burgess, John R, Clifton-Bligh, Roderick J
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Gland Neoplasms - epidemiology; Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - pathology; Adult; Aged; Australia; Australia - epidemiology; Child; Development and progression; Genetics; Germ-Line Mutation; Humans; Metastasis; Middle Aged; Mortality; Mutation; Online Only; Paraganglioma - diagnosis; Paraganglioma - epidemiology; Paraganglioma - genetics; Patient outcomes; Prospective Studies; Retrospective Studies; Succinate Dehydrogenase - genetics; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgac019

Carriers of succinate dehydrogenase type B (SDHB) pathogenic variants (PVs) are at risk of pheochromocytoma and paraganglioma (PPGL) from a young age. It is widely recommended carriers enter a surveillance program to detect tumors, but there are limited studies addressing outcomes of surveillance protocols for SDHB PV carriers. The purpose of this study was to describe surveillance-detected (s-d) tumors in SDHB PV carriers enrolled in a surveillance program and to compare their outcomes to probands. This was a multicenter study of SDHB PV carriers with at least 1 surveillance episode (clinical, biochemical, imaging) in Australian genetics clinics. Data were collected by both retrospective and ongoing prospective follow-up. Median duration of follow-up was 6.0 years. 181 SDHB PV carriers (33 probands and 148 nonprobands) were assessed. Tumors were detected in 20% of nonprobands undergoing surveillance (age range 9-76 years). Estimated 10-year metastasis-free survival was 66% for probands and 84% for nonprobands with s-d tumors (P = .027). S-d tumors were smaller than those in probands (median 27 mm vs 45 mm respectively, P = .001). Tumor size ≥40 mm was associated with progression to metastatic disease (OR 16.9, 95% CI 2.3-187.9, P = .001). Patients with s-d tumors had lower mortality compared to probands: 10-year overall survival was 79% for probands and 100% for nonprobands (P = .029). SDHB carriers with s-d tumors had smaller tumors, reduced risk of metastatic disease, and lower mortality than probands. Our results suggest that SDHB PV carriers should undertake surveillance to improve clinical outcomes.