SDHC phaeochromocytoma and paraganglioma: A UK‐wide case series
Year: 2021
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported. DESIGN: This retrospective case series collated data from 18 UK Genetics and Endocrinology departments. PATIENTS: Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included. MEASUREMENTS: Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation. RESULTS: We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11-79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79-0.99) in probands, and 0.16 (CI: 0-0.31) in non-probands, respectively. CONCLUSIONS: This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance.
Source: Clinical Endocrinology
DOI: 10.1111/cen.14594
Authors: Sophie T. Williams, Prodromos Chatzikyriakou, Paul V. Carroll, Barbara M. McGowan, Anand Velusamy, Gemma White, Rupert Obholzer, Scott Akker, Nicola Tufton, Ruth T. Casey, Eamonn R. Maher, Soo‐Mi Park, Mary Porteous, Rebecca Dyer, Tricia Tan, Florian Wernig, Angela F. Brady, Monika Kosicka‐Slawinska, Benjamin C. Whitelaw, Huw Dorkins, Fiona Lalloo, Paul Brennan, Joseph Carlow, Richard Martin, Anna L. Mitchell, Rachel Harrison, Lara Hawkes, John Newell‐Price, Alan Kelsall, Rebecca Igbokwe, Julian Adlard, Schaida Schirwani, Rosemarie Davidson, Patrick J. Morrison, Teng‐Teng Chung, Christopher Bowles, Louise Izatt
Institutions: Guy's Hospital, King's College London, University of Sheffield, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, St Bartholomew's Hospital, Barts Health NHS Trust, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Western General Hospital, Imperial College Healthcare NHS Trust, Northwick Park Hospital, King's College Hospital, Leicester Royal Infirmary, St Mary's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Churchill Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Birmingham Women's Hospital, Chapel Allerton Hospital, Queen Elizabeth University Hospital, Belfast City Hospital, University College Hospital, University College London Hospitals NHS Foundation Trust, University College London, Royal Devon and Exeter Hospital
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G377382894, G6077662935, G8378319365
OpenAlex ID: W3201022176