Endocrine Abstracts

Background: Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours arising from the adrenal medulla or extra-adrenal sympathetic and parasympathetic paraganglia. Paediatric cases account for only 10–20% of all detected cases of PPGL. Approximately 70–80% of PPGL in children are caused by an inherited pathogenic variant in one of at least 25 tumour susceptibility genes. Thus, germline genetic testing has high priority in the diagnostic work-up and guides personalized diagnostics, management, therapeutic and surveillance strategies in children and adolescents with PPGL.

Methods: Medical records were retrospectively analysed for paediatric patients followed in the paediatric neuroendocrine clinic at the Evelina Children’s Hospital, London between 2013 and 2025.

Results: We describe a case series of 6 paediatric patients (5/6 male) diagnosed with PCC (n = 4) and PPGL (n = 2) at median age of 10.74 (09.6-16.4) years, through histopathological confirmation. Routine PPGL surveillance detected 2/6 with known PPGL genetic susceptibility. The majority had symptomatic presentation: 3/6 hypertension, 1/6 transient weakness of the tongue and hearing loss. Histopathology report incidentally confirmed the diagnosis in 1/6 who underwent nephrectomy for unilateral kidney dysplasia due to chronic hypertension without undergoing endocrine work-up.4/6 had elevated plasma normetadrenaline levels and 1/6 had elevated plasma methoxytyramine levels. 4/6 had unilateral non-malignant PCC; 1/6 developed a second PCC in the other adrenal gland 1.6 years after the first. 5/6 had germline mutations (3/6 SDHB; 2/6 VHL). 1/6 had somatic VHL mutation on tumour analysis. 2/6 were diagnosed as a part of the cascade screening and in 1/6 the screening of the relatives led to the mother being diagnosed with the same mutation.

Conclusion: In paediatric patients with confirmed hereditary PPGL, lifelong follow-up is essential to screen for both metastatic disease and metachronous tumours or syndrome-related pathologies. The long-term surveillance protocols should be tailored to the specific pathogenic variant. Cascade genetic testing in the wider family is required, as 4 of these paediatric cases were the first PPGL presentation in their family. In all cases the pathogenic variant was confirmed as being inherited from a parent. The penetrance of PPGL in non-index cases is gene-dependent.