medwireNews: A European Standard Clinical Practice Guidance has been published in the European Journal of Endocrinology on the diagnosis and treatment of adrenal and extra-adrenal paragangliomas (PGLs) in children and adolescents.
The multidisciplinary panel of the European Cooperative Study Group for Paediatric Rare Tumours says their guidance complements the 2024 international consensus statement on paediatric PGLs by accounting for region-specific factors, and highlighting “actionable pathways tailored to European systems, integration into rare-tumour registries, biobanking and molecular networks, and harmonized workflows in European clinical practice.”
Michaela Kuhlen (University of Augsburg, Germany) and co-authors say that a “high index of clinical suspicion” and a “structured and multidisciplinary diagnostic approach” is required for PGLs in children and adolescents due to “their rarity and often subtle or intermittent manifestations” of excess catecholamine.
The recommendations for initial clinical evaluation detail clinical signs and symptoms, assessment of family history and syndromic features, and physical examination, followed by first-line biochemical confirmation via measurement of plasma-free metanephrine and normetanephrine.
Categorising tumours by adrenergic, noradrenergic or dopaminergic phenotype “may provide clues to tumour site, heritable background, or metastatic potential”, the authors say, albeit that these “are not definitive and must always be interpreted in conjunction with imaging and genetic testing.”
Anatomical imaging is essential for confirmation of diagnosis and treatment planning, they continue, while different types of functional imaging are recommended for patients with suspected multifocal or metastatic disease, or in the presence of genetic or biochemical markers associated with a high risk of metastasis.
The guidance emphasizes the role of genetic testing for paediatric PGL, which “should be considered hereditary until proven otherwise” due to the high proportion of patients with germline pathogenic variants, while somatic tumour sequencing and somatic profiling may also be useful.
Turning to treatment, the authors detail preoperative management advice on the use of alpha-adrenergic blockade and cardiovascular assessment, as well as imaging and biochemistry to guide surgical approach. Cortical-sparing adrenalectomy is recommended for synchronous bilateral adrenal PGL, especially in children with hereditary syndromes, but not indicated for children with SDHB pathogenic variants.
Minimally invasive adrenalectomy is preferred for localized tumours, whereas open surgery may be required for technically challenging or anatomically complex disease and patients with local invasion, the authors say. They emphasize that “[w]henever feasible, children should be referred to expert centres to optimize outcomes”, including for resection of extra-adrenal paragangliomas.
Metastatic disease occurs in 10–20% of patients overall and “watchful waiting” may be “appropriate” for those with asymptomatic, indolent disease, state Kuhlen and co-workers. However, up to 50% of those with hereditary disease may develop metastases and treatment is indicated for symptomatic and progressive metastases. The guidance discusses the need for tailored management of metastases using radionuclide therapy, other systemic agents such as targeted therapies (eg, tyrosine kinase inhibitors), focal therapies and palliative care.
“Given the lifelong risk of recurrence, development of new primary tumours, and metastatic progression – particularly in those with hereditary PGL – long-term follow-up is essential”, including a careful handover of information during transition to adult care, the guidance recommends.
This may include lifelong biochemical monitoring, repeated magnetic resonance imaging, and syndrome-specific surveillance, such as screening for medullary thyroid carcinoma and parathyroid disease in children with RET alterations.
“While these recommendations reflect current best practices, several aspects of paediatric PGL remain under-researched”, the authors conclude.
“Ongoing collaboration across European and international networks is essential to strengthen the evidence base, address remaining uncertainties, and improve outcomes for affected children, adolescents, and families.”
By Lynda Williams
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