Phaeochromocytomas/paragangliomas and adverse clinical outcomes in patients with Neurofibromatosis type 1

Abstract

IntroductionPhaeochromocytomas/paragangliomas (PHAEO/PG) are linked to hereditary syndromes including Neurofibromatosis type 1 (NF-1). Current guidelines do not recommend biochemical screening for PHAEO/PG in asymptomatic or normotensive patients with NF-1. This strategy may miss preventable morbidities in those patients who ultimately present with symptomatic PHAEO/PG. Our aim was to review the literature and extract data on mode of presentation and the incidence of reported adverse outcomes.MethodsPubMed and EMBASE literature search using the keywords ‘Phaeochromocytoma’, ‘Paraganglioma’ and ‘Neurofibromatosis’ was performed looking for reported cases from 2000 to 2018.ResultsSeventy-three reports of NF-1 patients with PHAEO/PG were found. Patients were predominately women (n = 40) with a median age of 46 years (range 16–82). PHAEO/PG was found incidentally in most patients, 36/73 did not present with typical symptoms while 27 patients were normotensive at diagnosis. Thirty-one patients had adverse outcomes including metastases and death.ConclusionGiven the protean presentation of PHAEO/PG, relying on symptomology and blood pressure status as triggers for screening, is associated with adverse outcomes. Further studies are required to ascertain whether biochemical screening in asymptomatic and normotensive patients with NF-1 can reduce the rate of adverse outcomes.

Clinical Presentation and Outcomes of Phaeochromocytomas/Paragangliomas in Neurofibromatosis Type 1

“…A recent review of all published isolated case reports of PHAEO/PG in patients with NF1 found at least 73 cases; 36/73 did not present with any of classical symptoms while 27/73 were normotensive at the time of PHAEO/PG diagnosis. 33 Furthermore, it was found that 31/73 of patients presented with life-threatening complications and interestingly, the majority were relatively young (age <40 years). These findings, in contrast to Képénékian et al, 20 would favour considering screening at an earlier age.…”

Screening for Hereditary Pheochromocytoma in a Patient with Neurofibromatosis Type 1: A Case Report

“…In English-language literature there are 73 case reports from the last 18 years. 30 In these cases, PHEO was more prevalent in women,…”

“…9,11,19,27 Compared with VHL and MEN2, PHEO in NF1 is more frequently unilateral (90% of cases), diagnosed incidentally, later in life and in patients with no familial history. 9,11,19,27,29,30 These differences might be related to the fact that current guidelines do not recommend routine biochemical or imaging screening of PHEO in asymptomatic/normotensive patients with NF1, despite the recommendation of doing it for patients with VHL or MEN2. 31 Recent studies reinforce the idea that PHEO prevalence in NF1 is underestimated and it may have atypical presentation (asymptomatic/normotensive or associated with non-specific symptoms).…”

“…Most of these are life-threatening cardiovascular complications that result from PHEO crisis triggered by tumour manipulation, pregnancy, drugs or metastatic disease. 11,27,30,[32][33][34] Furthermore, patients with PHEO associated with NF1 have more intraoperative hypertension variability and perioperative complications than patients with other genetic syndromes. 35 As a preventive measure, authors highlight the important role of routine screening in the absence of hypertension or classical symptoms, particularly prior to elective surgeries, during preconception planning or early in pregnancy.…”

“…35 As a preventive measure, authors highlight the important role of routine screening in the absence of hypertension or classical symptoms, particularly prior to elective surgeries, during preconception planning or early in pregnancy. 11,27,29,30,32,34 For biochemical diagnosis it is necessary to confirm the inappropriately elevated secretion of catecholamines and its metabolites through free plasma metanephrines or fractionated urinary metanephrines.…”