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Hereditary Cushing’s syndrome caused by primary bilateral macronodular adrenal hyperplasia due to ARMC5 mutation with concomitant primary hyperparathyroidism: the first known case in Russia

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Abstract


Primary bilateral macronodular adrenal hyperplasia (PBMAH), a genetically heterogeneous disease, is a rare cause of Cushing’s syndrome. Until recently, few cases were attributed to mutations in known genes. However, in 2013, ARMC5, a newly discovered tumor suppressor gene, was identified. Further studies have shown that mutations in the ARMC5 gene are found in 25–55% of all PBMAH cases.

This article describes a clinical case of hereditary Cushing’s syndrome caused by PBMAH in a 37-year old patient. The patient’s family history is remarkable for the presence of Cushing’s syndrome and PBMAH in the patient’s mother. Bilateral adrenalectomy was performed as the treatment of choice. Genetic analysis using whole-exome sequencing confirmed the hereditary cause of the disease, revealing a germline heterozygous mutation in the ARMC5 gene. The patient also had concomitant mild primary hyperparathyroidism, which had not been observed before in genetic carriers with the ARMC5 mutation.


Elizaveta O. Mamedova

Endocrinology Research Centre

Author for correspondence.
Email: lilybet@mail.ru
ORCID iD: 0000-0002-9783-3599
SPIN-code: 3904-6017

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Evgeny V. Vasilyev

Endocrinology Research Centre

Email: vas-evg@yandex.ru
ORCID iD: 0000-0003-1107-362X
SPIN-code: 5767-1569

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

PhD

Vasily M. Petrov

Endocrinology Research Centre

Email: petrov.vasily@gmail.com
ORCID iD: 0000-0002-0520-9132
SPIN-code: 4358-2147

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

PhD

Natalya S. Izmailova

Endocrinology Research Centre

Email: nizm2013@mail.ru
ORCID iD: 0000-0002-4713-5661
SPIN-code: 1984-1519

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Svetlana A. Buryakina

Endocrinology Research Centre

Email: sburyakina@yandex.ru
ORCID iD: 0000-0001-9065-7791
SPIN-code: 5675-0651

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Liudmila Ya. Rozhinskaya

Endocrinology Research Centre

Email: lrozhinskaya@gmail.com
ORCID iD: 0000-0001-7041-0732
SPIN-code: 5691-7775

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, Professor

Anatoly N. Tiulpakov

Endocrinology Research Centre

Email: anatolytiulpakov@gmail.com
ORCID iD: 0000-0001-8500-4841
SPIN-code: 8396-1798

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Zhanna E. Belaya

Endocrinology Research Centre

Email: jannabelaya@gmail.com
ORCID iD: 0000-0002-6674-6441
SPIN-code: 4746-7173

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

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Supplementary files

Supplementary Files Action
1. Fig. 1. MSCT of the adrenal glands of the patient Y., arterial phase, axial projection (the adrenal glands are indicated by arrows). View (395KB) Indexing metadata
2. Fig. 2. MSCT of the adrenal glands of the patient Y., arterial phase, coronary projection (the adrenal glands are indicated by arrows). View (554KB) Indexing metadata
3. Fig. 3. Bilateral macronodular hyperplasia of the adrenal glands, macropreparation. In enlarged adrenal glandslarge yellow nodes are determined. a - the right adrenal gland; b - left adrenal gland. View (984KB) Indexing metadata
4. Fig. 4. Bilateral macronodular hyperplasia of the adrenal glands, microslide (stained with hematoxylin and eosin, magnification × 50, × 100, × 200). a - some nodes are encapsulated and have connective tissue trabeculae; b, c - nodes are built from large bright cells, merging into strands and clusters. View (1MB) Indexing metadata

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Copyright (c) 2019 Mamedova E.O., Vasilyev E.V., Petrov V.M., Izmailova N.S., Buryakina S.A., Rozhinskaya L.Y., Tiulpakov A.N., Belaya Z.E.

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