Genetic Dissection of Primary Aldosteronism in a Patient With MEN1 and Ipsilateral Adrenocortical Carcinoma and Adenoma.

Autor:	Parisien-La Salle S; Division of Endocrinology, Department of Medicine, Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada., Corbeil G; Division of Endocrinology, Department of Medicine, Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada., El-Haffaf Z; Division of Genetics, Department of Medicine, Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada., Duranceau C; Division of Endocrinology, Department of Medicine, Chicoutimi Hospital, Université du Québec à Chicoutimi, Chicoutimi, QC, H2X 0C1, Canada., Latour M; Department of Pathology and Cellular Biology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada., Karakiewicz PI; Division of Urology, Department of Surgery, Centre Hospitalier de l'Université de Montréal, Montréal, QC, H2X 0C1, Canada., Lacroix A; Division of Endocrinology, Department of Medicine, Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada., Bourdeau I; Division of Endocrinology, Department of Medicine, Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, H2X 0C1, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 Dec 17; Vol. 108 (1), pp. 26-32.
DOI:	10.1210/clinem/dgac564
Abstrakt:	Background: Adrenal tumors are found in up to 40% of patients with multiple endocrine neoplasia type 1 (MEN1). However, adrenocortical carcinomas (ACC) and primary aldosteronism (PA) are rare in MEN1. Case: A 48-year-old woman known to have primary hyperparathyroidism and hypertension with hypokalemia was referred for a right complex 8-cm adrenal mass with a 38.1 SUVmax uptake on 18F-FDG PET/CT. PA was confirmed by saline suppression test (aldosterone 1948 pmol/L-1675 pmol/L; normal range [N]: <165 post saline infusion) and suppressed renin levels (<5 ng/L; N: 5-20). Catecholamines, androgens, 24-hour urinary cortisol, and pituitary panel were normal. A right open adrenalectomy revealed a concomitant 4-cm oncocytic ACC and a 2.3-cm adrenocortical adenoma. Immunohistochemistry showed high expression of aldosterone synthase protein in the adenoma but not in the ACC, supporting excess aldosterone production by the adenoma. Genetic Analysis: After genetic counseling, the patient underwent genetic analysis of leucocyte and tumoral DNA. Sequencing of MEN1 revealed a heterozygous germline pathogenic variant in MEN1 (c.1556delC, p.Pro519Leufs*40). The wild-type MEN1 allele was lost in the tumoral DNA of both the resected adenoma and carcinoma. Sequencing analysis of driver genes in PA revealed a somatic pathogenic variant in exon 2 of the KCNJ5 gene (c.451G>A, p.Gly151Arg) only in the aldosteronoma. Conclusion: To our knowledge, we describe the first case of adrenal collision tumors in a patient carrying a germline pathogenic variant of the MEN1 gene associated with MEN1 loss of heterozygosity in both oncocytic ACC and adenoma and a somatic KCNJ5 pathogenic variant leading to aldosterone-producing adenoma. This case gives new insights on adrenal tumorigenesis in MEN1 patients. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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