The Biochemical Spectrum of Pheochromocytoma

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that secrete catecholamines. While classic symptoms such as palpitations, sweating, and headaches may occur, many patients exhibit nonspecific or mild signs due to intermittent or low-level catecholamine secretion. This variability complicates diagnosis and increases the risk of missed or delayed detection. In this case series, we describe four patients with PPGLs demonstrating variable catecholamine secretion from overt secretion to low levels of secretion, where a clinician might incorrectly exclude the diagnosis of PPGL based on a biochemical test within the normal range. Key elements to improve detection of PPGLs from patients with minimal catecholamine secretion include a careful history on clinical symptoms of catecholamine excess, serial biochemical testing over time, utilizing nuclear medicine studies, Hounsfield units >10 from computed tomography (CT), and family history of PPGLs. Our findings from this case series help the clinician to appreciate the broad biochemical spectrum of PPGLs from no detectable or minimal catecholamine secretion to overt secretion, and how to navigate such an evaluation.