Background: PCC and PGL are rare in CYP. National childrens registry data reveal an annual incidence of 0.2 and 0.3 per million in 59 and 1014 year age groups respectively. Almost all result from a genetic predisposition, can present with non-specific symptoms, and represent a significant management challenge.
Aims: We aimed to provide the first interdisciplinary national management guidelines using the AGREEII framework for CYP with confirmed or suspected PCC/PGL, and endorsed by the Royal College of Paediatrics and Child Health, UK Childrens Cancer & Leukaemia Group and the British Society for Paediatric Endocrinology & Diabetes.
Methods: 113 PICO clinical questions were formulated by a specialist GDG, and systematic literature searches conducted via Ovid MEDLINE and Cochrane Library databases identifying 526 articles. Publications were filtered and 397 reviewed using GRADE. Where evidence was lacking or conflicting, a two-stage international Delphi consensus process was conducted to make recommendations.
Results: 39 recommendations on assessment, investigations, medical/surgical management and long-term follow-up of survivors are made; 21 were sent to consensus and achieved agreement. Importantly, the GDG recommend CYP with PCC/PGL are managed in a specialist endocrine centre, linked to tertiary paediatric oncology, by a designated, age-appropriate multidisciplinary team and experienced lead clinician. Clinical assessment, including a three-generation family history, should be targeted to identify genetically determined PCC/PGL (Von Hippel Lindau (VHL), familial paraganglioma (mutations in succinate dehydrogenase genes, SDHx), Multiple Endocrine Neoplasia 2, Neurofibromatosis 1), and genetic testing offered for all CYP with PCC/PGL after counselling. For CYP who undergo bilateral/completion adrenalectomy or cortical sparing surgery, peri-operative steroid replacement should be led by a nominated endocrinologist. Subspecialist, including critical care, input is required for timely identification of peri-operative hypertension, hypotension and hypoglycaemia (the latter two prompting exclusion of hypocorti-solism/adrenal crisis and commencement of stress-dose steroid). CYP who have undergone adrenocortical sparing surgery should continue maintenance steroid replacement until adrenocortical reserve is tested post-operatively. Patients with SDHB mutations/VHL have a high risk of recurrent disease and malignancy, however all CYP diagnosed with PCC/PGL should have life-long follow up because of the propensity for new events.
Conclusions: These guidelines provide the first evidence- and consensus-based national recommendations for the management of PCC/PGL in CYP, and highlight a need for further audit and research in this rare, but potentially serious, condition. Their implementation should improve the quality of care and long-term health-related survival of CYP with PCC/PGL.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology