ECE2015 Guided Posters Endocrine tumours and neoplasia – Adrenal Tumour (7 abstracts)
Penetrance and optimal surveillance for SDHB mutation carriers
Karin Eijkelenkamp 1 , Thamara E Osinga 1 , Mirjam M de Jong 2 , Wim J Sluiter 1 , Robin P F Dullaart 1 , Thera P Links 1 , Michiel N Kerstens 1 & Anouk N A van der Horst-Schrivers 1
1Department of Endocrinology and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands; 2Department of Clinical Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Context: Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to head and neck paraganglioma (HNPGL), sympathetic PGL, phaeochromocytoma and renal cell carcinoma for which regular surveillance is required. SDHB-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis stating that the combination of an inactivating germline mutation as a first hit and somatic loss of function of the wild type allele as a second hit is essential for tumor development. The aim of this study was to assess the penetrance and optimal surveillance for different manifestations of SDHB mutation carriers.
Patients and methods: This study included all SDHB mutation carriers (18 index cases from 20 non-consanguineous families) who were prospectively followed at the department of Endocrinology at the University Medical Center of Groningen. Kaplan Meier curves were used to assess the penetrance. Poisson distribution model was used to calculate the hit rate and average time to detect the first and subsequent manifestation, to assess the optimal age to start surveillance and intervals.
Results: Eighty-three SDHB mutation carriers (33 men and 50 women) were included. Twenty-three mutation carriers (28%) had a manifestation, of whom 18 carriers (22%) were index patients. First manifestations included HNPGL (n=15), sympathetic PGL (n=9) and phaeochromocytoma (n=1), with an overall penetrance 35% at the age of 60 years. The optimal age to start surveillance for HNPGL was age 24 years, with a subsequent interval of 4 years.
Conclusion: This study emphasises a relatively low penetrance of disease in SDHB mutation carriers. By using a Poisson distribution model a more accurate estimation of the age to initiate surveillance and subsequent intervals is provided for HNPGL, suggesting that guideline recommendation regarding the screening of these mutation carriers might need to be revised.
Volume 37
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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