Pheochromocytoma: A Genetic and Diagnostic Update

Leilani B. Mercado-Asis, MD, PhD, MPH; Katherine I. Wolf; Ivana Jochmanova, MD; David Taïeb, MD

Disclosures

Endocr Pract. 2018;24(1):78-90. 

In This Article

Abstract and Introduction

Abstract

Objective: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathologic studies are performed to prove, localize, treat, and monitor disease progression. Improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (<1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment.

Methods: This review outlines the most updated approach to PPGL patients and presents a new diagnostic protocol for physicians to increase earlier tumor identification and accurately assess metastatic behavior.

Conclusion: We present the most recent advances in genetics, epigenetics, metabolomics, biochemical, and imaging diagnoses of this rare tumor to properly assess disease, decide treatment options, and manage follow-up. We also elaborate on new therapeutic perspectives in these very rare neoplastic entities.

Introduction

Pheochromocytomas and paragangliomas (PPGLs) are chromaffin cell neuroendocrine tumors characterized by catecholamine synthesis, release, and metabolism in the adrenal medulla or extra-adrenal sympathetic or parasympathetic paraganglia, respectively.[1] With a prevalence of 0.1 to 0.6% in hypertensive adults and an annual general population incidence of 1 per 100,000, clinical suspicion remains the primary indicator for initiating a biochemical workup to confirm a diagnosis of PPGL.[2]

Patients most commonly present with recurring episodes of hypertension, palpitations, profuse diaphoresis, and pallor.[3,4] Less frequently, PPGL may manifest as nausea, vomiting, flushing, and weight loss. In young patients with normal body weight, the presence of hypertension with diabetes mellitus may suggest PPGL.[5] Recently, Pourian et al established a clinical symptomatology likelihood ratio, which showed that only palpitations, headache, and diaphoresis are significant when considering a possible PPGL diagnosis.[6] Although the general symptoms remain nonspecific, catecholamine-induced organ damage, particularly to the endocrine, metabolic, and cardiovascular systems, should indicate a full diagnostic workup for PPGL. Improper or delayed PPGL diagnosis has long been associated with the destructive results of a sudden catecholamine release that induce adverse cardiovascular events.[7,8] Ferreira et al performed the first prospective study on the extent of cardiac involvement in PPGL patients.[9] Unlike previous reports detailing the reversal of catecholamine-induced myocarditis following removal of the unsuspected tumor,[10] the authors discovered persistent subclinical systolic and diastolic dysfunction in addition to markers for focal and diffuse fibrosis, as well as cardiac abnormalities distinct from the hypertensive control subjects used throughout the study.[9] In the future, early identification of cardiac catecholamine toxicity could predict potentially disastrous cardiovascular events and prevent long-term myocardial alterations.[9]

The present review highlights the latest genetic, metabolomic, biochemical, and functional imaging approaches to update the diagnostic approach for hereditary and sporadic PPGLs.

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