Endocrine Abstracts

Since 2019 the nationally commissioned NHS Genomic Medicine Service (GMC) has provided the opportunity for endocrine doctors to directly request genetic testing, without the need to involve clinical genetics service, known as ‘mainstreaming’. The tests are R coded and have specific eligibility criteria. At KCH we have developed a small endocrine genetics clinic. We conducted an audit/service review to see the range of tests that were being requested and the extent pathogenic variants were detected.

Methods: We reviewed the most recent 100 cases seen in our endocrine genetics clinic, from Feb 2023 to June 2025, and recorded the test completed and whether a pathogenic variant was detected. Patients with pathogenic variants were referred on to the local clinical genetics service for cascade testing where appropriate.

Results: The most common test requests are for Paraganglioma, MEN1, MEN2 and Li-Fraumeni testing, in the context of adrenal cancer. Pathogenic variants were detected in 21% of cases, these were predominantly paraganglioma cases (12/34), but also MEN1 (2/10), ARMC5 in the context bilateral adrenal nodularity (2/3) and Lynch syndrome in adrenal cancer (1/1). The rate of unexpected findings and variants of uncertain significance (VUS) was low at 2%. Examples include 2q microdeletion (on R26 test) and VUS of the AIP gene in R217 test.

Discussion: The range of tests requested reflects the clinical caseload of the department, with a large number of paragangliomas, adrenal cancer cases and pituitary tumours. Paediatric cases fall under a separate pathway. The highest rate of detection of pathogenic variants was in PGL at 35%, reflecting the high heritability of these tumours. The audit confirms the importance of genetic testing early in the pathway to inform care of affected individuals and to enable cascade testing in family members. The rate of unexpected genetic findings was low, and not clinically challenging.