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Normotensive Incidentally Discovered Pheochromocytomas Display Specific Biochemical, Cellular, and Molecular Characteristics

Abstract : Design: This was a retrospective cohort recruited from 2001 to 2011 in 2 tertiary care medical departments. Patients and Methods: Clinical, biological, and radiological investigations performed in 96 consecutive patients with sporadic unilateral pheochromocytomas were examined; 47 patients had overt pheochromocytomas responsible for hypertension. Among the patients with incidental pheochromocytomas, 28 had hypertension and 21 were normotensive (NIPs). A total of 62 tumors were examined to determine the Pheochromocytoma of the Adrenal Gland Scale Score, and 29 were studied for the expression of 16 genes involved in chromaffin cell function. Context: A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIPs) are poory known. Objective: The purpose of this work was to assess the clinical, hormonal, histological, and molecular features of NIPs. Results: Tumor size and metaiodobenzylguanidine (MIBG) scintigraphy results were similar for hypertensive pheochromocytomas (HPs) and NIPs. Patients with NIPs displayed reduced summed levels of urinary catecholamines and metanephrines and, more specifically, reduced levels of adrenaline and metadrenaline compared with those of patients with HPs (P < .001). Urinary metanephrines had 98% diagnostic sensitivity in patients with HPs and only 75% in patients with NIPs (P < .01). Tumor diameter positively correlated with the total amount of urinary concentrations of metanephrines in patients with HPs (P < .001) but not in patients with NIPs. NIPs displayed global decreased chromaffin gene expression (reaching significance for 5 of them) and 2 corresponding proteins (phenylethanolamine N-methyltransferase and secretogranin II) and a significant increase in the cellularity, mitotic activity, and presence of atypical mitosis (P < .05). Conclusions: NIPs differ from pheochromocytomas responsible for hypertension and display features of altered chromaffin differentiation. These tumors may be misdiagnosed with the use of the usual biological diagnostic tools.
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Magalie Haissaguerre, Maïté Courel, Sophie Denost, Laurent yon, Christophe Dubessy, et al.. Normotensive Incidentally Discovered Pheochromocytomas Display Specific Biochemical, Cellular, and Molecular Characteristics. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2013, 98 (11), pp.4346-4354. ⟨10.1210/jc.2013-1844⟩. ⟨hal-01706417⟩



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