Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening

Abstract

BackgroundPheochromocytomas and Paragangliomas (PCC/PGL) are rare endocrine tumors that are mostly benign, but often hormone producing, causing significant morbidity and mortality due to excess catecholamine secretion and cardiovascular crises. It is estimated that 30% of PCC/PGL are due to germline mutations, including Neurofibromatosis type 1 (NF1). There is little published data describing the phenotype of NF1-associated PCC/PGL and there are no established recommendations for PCC/PGL screening in NF1.MethodsWe conducted a retrospective chart review of 17 patients with NF1-associated PCC/PGL who received care at a large academic referral center between the years of 1992–2016.ResultsAverage age of diagnosis was 42 years old. Both genders were equally affected. Average tumor size was 3.9 cm. Nine patients were hypertensive; one had orthostatic hypotension; three had tachycardia; the remaining two patients had normal BP and HR. Most tumors were benign, unilateral adrenal tumors that were hormonally active. Two had metastatic disease. Six patients experienced cardiovascular crises; three of which occurred during elective surgeries for neurofibroma removal, and a fourth occurred during labor and delivery.ConclusionThese data highlight the importance of screening for PCC/PGL in NF1, especially prior to surgical procedures and pregnancy, labor and delivery as these events can trigger a cardiovascular crisis. Screening is easily accomplished with plasma or urine free fractionated metanephrine levels.Electronic supplementary materialThe online version of this article (10.1186/s40842-018-0065-4) contains supplementary material, which is available to authorized users.

Genetic Counseling for Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis—Practice Resource of the National Society of Genetic Counselors

“…Additional reproductive considerations exist for women with NF1, as they are at greater risk for antenatal and peripartum complications (Leppavirta et al., 2017; Petr & Else, 2018; Terry et al., 2013). Complications include gestational hypertension, preeclampsia, placental abruption, intrauterine growth retardation, cerebrovascular disease, cardiovascular crisis associated with pheochromocytomas and paragangliomas, preterm labor, and the need for cesarean delivery.…”

‘Adrenal rush’ in a patient with Neurofibromatosis-1

“…In another study where NF-1 patients over the age of 18 years were imaged for PHEO, the majority of the patients diagnosed with PHEO-whether [11]. Another important fact is that normotensive NF-1 patients with pheochromocytoma have a similar postoperative mortality rate when compared to those with hypertension [12]. Thus, failure to diagnose an underlying PHEO in NF-1 patients can have devastating consequences.…”

“…However, the frequency of screening can be every 3 years instead of every year, as the prevalence of PHEO is lower in NF1 compared to VHL and MEN syndromes [13]. In addition, some authorities have favored the routine screening of pheochromocytoma in all patients with NF-1 prior to any surgical procedures and/or pregnancy [12].…”

Isolated Pheochromocytoma in a 73-Year-Old Man With No Clinical Manifestations of Type 1 Neurofibromatosis Carrying an Unsuspected Deletion of the Entire NF1 Gene

“…This disease causes multi-organ involvement, which can include PHEOs in 0.1–7% (2, 10). The incidence might be underestimated due to the lack of formal recommendations to universally screen biochemically NF1 patients for PHEOs, as there are in other genetic syndromes such as Von-Hippel-Lindau or MEN2 (10, 11). Recent data showed that 31% of PHEOs in NF1 are found incidentally and only 7.3% were diagnosed following biochemical testing (12).…”