Endocrine Abstracts

JOINT1288

Background: Phaeochromocytomas and paragangliomas have an annual incidence of 0. 5-2 cases per million children, with 70-80% linked to inherited pathogenic variants in tumour suppressor genes⁽¹⁾. An international consensus statement (2024) underscored the need for lifelong surveillance of asymptomatic variant carriers identified through family-based genetic testing, from childhood/early adulthood⁽¹⁾. Surveillance enhances early detection and timely management of tumours.

Methods: This retrospective audit analysed uptake and outcomes of annual surveillance offered to young people identified through family-based genetic testing and referred to Barts Health NHS Trust from 2019-2024.

Results: The audit included a population of 55 individuals aged 5-19. Of these, 48 (87%) had heterozygous variants in SDHB, 4 (7%) in SDHD, and 1 (2%) in each of SDHA, SDHC, and TMEM127. Of those aged under 10, each year, an average of 92% (range 82-100%) attended clinic reviews (face-to-face/telephone), 75% (range 42-93%) undertook 24-hour urinary metanephrine screening, and 94% (range 83-100%) attended for ultrasound neck/abdomen/pelvis. Of those aged 10 and over, each year, 85% (range 50-100%) attended clinic reviews (face-to-face/telephone), 82% (range 76-91%) had plasma metanephrines tested and 84% (range 75-91%) attended MRI scans (alternating MRI abdomen/pelvis and MRI neck/thorax/abdomen/pelvis). During the audit period, 2 patients, both SDHB variant carriers, had lesions identified on first surveillance. The first was diagnosed with a retroperitoneal paraganglioma (20x23x27mm) at age 8. 7, suspected following an elevated 24-hour urinary normetadrenaline/creatinine ratio at 851nmol/mol (normal <300nmol/mol), and confirmed by MRI. The second was diagnosed with a left adrenal phaeochromocytoma (28x22mm) at age 16. 9, detected on MRI. They had raised plasma normetanephrine at 1308pmol/l (normal <775pmol/l). Alpha-blocked resection was followed by 6-monthly imaging and plasma metanephrines for 5 and 1 years respectively. No recurrences/metastases have since been identified. Over this period, 27 of 202 scans conducted (ultrasound/MRI) showed unrelated incidental findings (22 individuals). 10 underwent further investigations and 1 required treatment. Work is ongoing to understand patient experiences and the psychological impact of screening on patients and their families.

Discussion: Within our cohort, the annual screening programme demonstrates good compliance and is effective at detecting lesions early. Since screening revealed pathology in children under 10, this supports early surveillance for variant carriers identified through family-based genetic testing.

References: 1. Casey RT, Hendriks E, Deal C, Waguespack SG, Wiegering V, Redlich A, et al. International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents. Nat Rev Endocrinol [Internet]. 2024 Dec 15;20(12):729–48. Available from:https://www. nature. com/articles/s41574-024-01024-5. [Accessed:30/08/2024]