Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome

Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare but treacherous catecholamine-producing tumors which, if overlooked or improperly treated, will almost invariably prove fatal. Patients with MEN2 PHEOs have a high incidence of paroxysmal attacks and a higher prevalence of hypertension and other cardiovascular problems than do patients with Von-Hippel-Lindau (VHL) PHEOs. Compared to measurements of deconjugated metanephrines, plasma concentrations of free metanephrines are relatively independent of renal function and therefore more suitable for diagnosis of PHEO/PGL. Recently, the focus of Positron Emission Tomography (PET) imaging for these tumors has been the localization of PHEO. Although a limited number of studies are available, [F-18]-fluorodopamine ([F-18]DA) PET has been found to be the best overall imaging modality in the localization of PHEO. For adrenal PHEOs, this method seems to be comparable to other functional modalities such as [F-18]-fluorodopa ([F-18]DOPA) PET or [I-123]-metaiodobenzylguanidine ([I-123]MIBG) scintigraphy. For extraadrenal PHEOs, data are limited and more extensive studies are needed. In patients with metastatic PHEO, the sensitivity of [F-18] DA PET is superior to [I-123] MIBG. The so called flip-flop imaging showing superiority of non-specific [F-18] flurodeoxyglucose (FDG) PET over specific [F-18] DA PET has been described in rapidly progressive, often metastatic SDHB-associated PHEOs. Whether these data reflect PHEO cell dedifferentiation (e.g. losing Norepinephrine Transporter - NET) or increased metabolic rate remains to be established.