Endocrine Abstracts

SDH mutations that contribute 15%–20% of PCC/PGL syndromes predispose to the development of tumours that originate from Adrenal, Parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. We conducted a retrospective analysis to identify the prevalence of PCC/PGL and elevated biomarkers during initial screening in patients newly identified as carrying a pathogenic SDH mutation.

Method: Data collection from our random cohort of patients with SDH mutations at Guy’s and St. Thomas’s NHS Foundation Trust. Following confirmation of a pathogenic SDH mutation, all patients had measurement of plasma Metanephrines and whole-body (incl. head & neck) MRI.

Results: Thirty-five adult patients (mean age 39 years; range 10–66) were included. All were asymptomatic and identified as carrying a mutation in SDH gene through family screening (3 with SDHA, 24 with SDHB, 3 with SDHC and 5 with SDHD). 10 of 35 patients (29% - 5 with SDHB mutation and 5 with SDHD mutation) had a tumour at initial screening. Tumour locations were as follows; Four head and neck (3 × SDHD, 1 × SDHB), five abdominal (2 × SDHD, 3 × SDHB) and one thoracic (SDHB). Four patients had elevated plasma Metanephrines at initial screening (11%), one of whom had a malignant thoracic PGL detected 6 months during follow up. (mutation in SDHB).

Conclusion: The tumour burden is high (29%) in these adult patients with SDH mutations during initial screening. Tumours involving the genes SDHD and SDHB were more prevalent and malignant potential is consistently prevalent in SDHB as reported in literature. Interestingly, few abdominal PGLs in our cohort were non-secretory. A multivariate analysis of our cohort of more than 500 patients will guide the screening and follow-up strategy for these patients long term.