A Laboratory Medicine Perspective on the Investigation of Phaeochromocytoma and Paraganglioma

Abstract

Phaeochromocytomas (PC) and sympathetic paragangliomas (PGL) are potentially malignant tumours arising from the adrenal medulla (PC) or elsewhere in the sympathetic nervous system (PGL). These tumours usually secrete catecholamines and are associated with significant morbidity and mortality, so accurate and timely diagnosis is essential. The initial diagnosis of phaeochromocytoma/paraganglioma (PPGL) is often dependent on biochemical testing. There is a range of pre-analytical, analytical and post-analytical factors influencing the analytical and diagnostic performance of biochemical tests for PPGL. Pre-analytical factors include patient preparation, sample handling and choice of test. Analytical factors include choice of methodology and the potential for analytical interference from medications and other compounds. Important factors in the post-analytical phase include provision of appropriate reference ranges, an understanding of the potential effects of various medications on metanephrine concentrations in urine and plasma and a consideration of PPGL prevalence in the patient population being tested. This article reviews these pre-analytical, analytical and post-analytical factors that must be understood in order to provide effective laboratory services for biochemical testing in the diagnosis of PPGL.

Keywords: metanephrines; paraganglioma; phaeochromocytoma.

Figure 1

PPGL genetic pre-disposition syndromes. Para-PGL = parasympathetic PGL. Symp-PGL = sympathetic PGL. PC = phaeochromocytoma. NET = neuroendocrine tumour. TCA = tricarboxylic acid.

Figure 2

Summary of catecholamine synthetic and metabolic pathways. TH = tyrosine hydroxylase, AAAD = aromatic L-amino acid decarboxylase, DBH = dopamine β-hydroxylase, PNMT = phenylethanolamine N-methyltransferase, COMT = catechol O-methyltransferase, MAO = monoamine oxidase. * Via other intermediates.

Figure 3

Summary of the relative advantages and disadvantages of different methodologies from measuring urine/plasma metanephrines.

Figure 4

Varying prevalence, positive predictive value and negative value in biochemical testing for PPGL in different patient populations.