Phaeochromocytoma/paragangliomas in patients with Neurofibromatosis-1: time to re-visit the clinical practice guidelines?
A Al-Sharefi1, U Javaid1, P Perros1, J Ealing2,3, P Truran4, S Nag5,
S Kamaruddin6, K Abouglila6, F Cains3, L Lewis3, R A James1
1Department of Endocrinology, The Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon-Tyne, UK; 2Manchester Centre for Clinical Neuroscience, Salford Royal NHS Foundation Trust, Manchester, UK; 3Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK; 4Department of Endocrine Surgery, The Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK; 5Department of Endocrinology, The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK; 6Department of Endocrinology, County Durham and Darlington NHS Foundation Trust, Durham, UK.
Introduction: Patients with neurofibromatosis type 1 (NF1) are at risk of developing phaeochromocytomas/paragangliomas (PHAEO/PG). Unlike in other familial PHAEO/PG syndromes, there are no published guidelines regarding screening in asymptomatic or normotensive patients with NF1. This strategy may be associated with preventable morbidities in those patients who ultimately present with symptomatic PHAEO/PG.
Objective: To describe the mode of presentation and the incidence of adverse clinical outcomes attributed to PHAEO/PG in NF1.
Methods: A retrospective study was performed in a tertiary referral centre in Northern England in collaboration with the national complex NF1 centre. Hospital records and databases between 1998–2018 were searched.
Results: Twenty-seven patients with NF1 and PHAEO/PG were identified. In all but one, PHAEO/PG was diagnosed after NF1. The median age at the time of diagnosis of PHAEO/PG was 43 years (range 22–65) and 21/27 (78%) were females. The diagnosis was mostly incidental in 13/27 (48%) while classical PHAEO/PG symptoms were found in 15/27 (56%), and hypertension was found in 14/27 (52%) of NF1 patients prior to PHAEO/PG diagnosis. No patient had undergone biochemical screening for PHAEO/PG. Metastatic disease was evident in 2/27 patients, 8 suffered potentially avoidable complications attributed to PHAEO/PG (including two deaths).
Conclusion: The course of PHAEO/PG
in NF1 is associated with an unpredictable presentation and potentially
avoidable adverse outcomes. We recommend that routine biochemical screening for
PHAEO/PG should be part of the care package offered to all patients with NF1 by
regular measurements of plasma free or urinary fractionated metanephrines
starting from early adolescence and
repeated every 3 years.