Prediction of Syndromic Pheochromocytoma and Paraganglioma Based on Biochemical Phenotype

Presentation Number: SUN 386
Date of Presentation: April 2nd, 2017

Qi Yan*1, Irina Bancos1, Lucinda M Gruber2, Cristian Bancos1, Travis J. McKenzie1 and William F Young Jr.1
1Mayo Clinic, Rochester, MN, 2Mayo Clinic School of Graduate Medical Education, Rochester, MN

Abstract

Background: Neurofibromatosis type 1 (NF1), multiple endocrine neoplasia type 2 (MEN2), and von Hippel Lindau (VHL) are the three most common genetic syndromes predisposing to pheochromocytoma and paraganglioma (PPGL). Patients diagnosed with PPGL in the context of VHL are thought to uniformly present with a noradrenergic biochemical phenotype, while PPGL in patients with MEN2 and NF1 present with an adrenergic biochemical phenotype.

Aim: To evaluate the accuracy of catecholamine biochemical phenotype in predicting the type of syndromic PPGL in patients with MEN2, VHL, and NF1.

Materials and Methods: We retrospectively reviewed medical records of patients with MEN2, NF1, and VHL who were diagnosed with PPGL between 1971 and 2016. To account for differences in assays over the years, measurements of norepinephrine, epinephrine, metanephrine, and normetanephrine were converted into Standard Scores (SS) (SS = [(measured value) – (maximum normal value)] / (maximum normal value)]).

Results: Of 121 patients (40 NF1, 48 MEN2, 33 VHL) who presented with PPGL, 102 (84%) had hypersecretion of catecholamines and metanephrines. The median SS for metanephrine was lower in patients with VHL as compared to NF1 and MEN2 (24-hr urine: -0.7 vs 4.0 and 1.6, respectively [P <0.05]; plasma: -0.8 vs 1.2 and 0.66, respectively [P<0.05]). The median SS for normetanephrine was higher in VHL as compared to NF1 and MEN2 (24-hr urine: 3.6 vs 0.8 and 0.9, respectively [P=0.08]; plasma: 7.8 vs 4.3 and 1.3, respectively [P<0.05]). However, 5 patients (15%) with VHL presented with an adrenergic biochemical phenotype with a metanephrine SS of 2.7-27.8. Three patients (6%) with MEN2 presented with a noradrenergic biochemical phenotype with a metanephrine SS<0.5 and a normetanephrine SS of 6.7,39, and 47.

Conclusion: Although predictive, the biochemical phenotype of PPGL in MEN2 and VHL lacks accuracy. Fifteen percent of patients diagnosed with PPGL in the context of VHL presented with an adrenergic biochemical phenotype and 6% of patients with MEN2 the PPGL had a noradrenergic phenotype.

 

Nothing to Disclose: QY, IB, LMG, CB, TJM, WFY Jr.