PMID- 36179244
OWN - NLM
STAT- MEDLINE
DCOM- 20221220
LR  - 20230201
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 108
IP  - 1
DP  - 2022 Dec 17
TI  - Genetic Dissection of Primary Aldosteronism in a Patient With MEN1 and 
      Ipsilateral Adrenocortical Carcinoma and Adenoma.
PG  - 26-32
LID - 10.1210/clinem/dgac564 [doi]
AB  - 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.
CI  - (c) 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.
FAU - Parisien-La Salle, Stefanie
AU  - Parisien-La Salle S
AUID- ORCID: 0000-0001-5960-4181
AD  - Division of Endocrinology, Department of Medicine, Research Center, Centre 
      hospitalier de l'Universite de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
FAU - Corbeil, Gilles
AU  - Corbeil G
AD  - Division of Endocrinology, Department of Medicine, Research Center, Centre 
      hospitalier de l'Universite de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
FAU - El-Haffaf, Zaki
AU  - El-Haffaf Z
AD  - Division of Genetics, Department of Medicine, Research Center, Centre hospitalier 
      de l'Universite de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
FAU - Duranceau, Caroline
AU  - Duranceau C
AD  - Division of Endocrinology, Department of Medicine, Chicoutimi Hospital, 
      Universite du Quebec a Chicoutimi, Chicoutimi, QC, H2X 0C1, Canada.
FAU - Latour, Mathieu
AU  - Latour M
AD  - Department of Pathology and Cellular Biology, Centre hospitalier de l'Universite 
      de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
FAU - Karakiewicz, Pierre I
AU  - Karakiewicz PI
AD  - Division of Urology, Department of Surgery, Centre Hospitalier de l'Universite de 
      Montreal, Montreal, QC, H2X 0C1, Canada.
FAU - Lacroix, Andre
AU  - Lacroix A
AUID- ORCID: 0000-0003-4137-3025
AD  - Division of Endocrinology, Department of Medicine, Research Center, Centre 
      hospitalier de l'Universite de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
FAU - Bourdeau, Isabelle
AU  - Bourdeau I
AUID- ORCID: 0000-0002-8000-4313
AD  - Division of Endocrinology, Department of Medicine, Research Center, Centre 
      hospitalier de l'Universite de Montreal (CHUM), Montreal, QC, H2X 0C1, Canada.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 4964P6T9RB (Aldosterone)
RN  - 0 (KCNJ5 protein, human)
RN  - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels)
SB  - IM
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - *Adrenocortical Carcinoma/complications/genetics/surgery
MH  - Aldosterone/metabolism
MH  - *Multiple Endocrine Neoplasia Type 1/complications
MH  - *Hyperaldosteronism/genetics/surgery
MH  - *Adrenal Cortex Neoplasms/complications/genetics/surgery
MH  - Positron Emission Tomography Computed Tomography
MH  - *Adrenocortical Adenoma/complications/genetics/surgery
MH  - *Adenoma/complications/genetics/surgery
MH  - *Adrenal Gland Neoplasms/complications/genetics/surgery
MH  - G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics
OTO - NOTNLM
OT  - MEN1
OT  - genetics
OT  - oncocytic adrenocortical carcinoma
OT  - primary aldosteronism
EDAT- 2022/10/01 06:00
MHDA- 2022/12/21 06:00
CRDT- 2022/09/30 15:53
PHST- 2022/05/05 00:00 [received]
PHST- 2022/10/01 06:00 [pubmed]
PHST- 2022/12/21 06:00 [medline]
PHST- 2022/09/30 15:53 [entrez]
AID - 6732503 [pii]
AID - 10.1210/clinem/dgac564 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Dec 17;108(1):26-32. doi: 10.1210/clinem/dgac564.