Differential diagnosis of hyperandrogenism

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Abstract

Background: Androgen-producing tumors represent an extremely rare group of hormonally active adrenal neoplasms. Their clinical course is characterized by hirsutism, menstrual irregularities, acne, virilization and other manifestations of hyperandrogenism. This condition should be differentially diagnosed with diseases such as polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), Itsenko–Cushing syndrome and adrogen-producing ovarian tumors, which are also characterized by androgen excess.

Case report: The presented clinical case is an example of long-term observation of a reproductive-aged woman with a clinical picture of hyperandrogenism and reproductive dysfunction; she received ineffective treatment for CAH and PCOS at different periods of her life. Multisteroid hormone analysis of blood serum by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), genetic testing combined with high-precision imaging techniques made it possible to establish the diagnosis of androgen-producing adrenal mass as the underlying cause of the disease more than 20 years after the appearance of the first symptoms. After performing adrenalectomy for the tumor, the level of androgens and their metabolites became normal, and the menstrual cycle restored.

Conclusion: Patients with manifestations of hyperandrogenism should have laboratory evaluation of possible hormonal disorders, imaging of the adrenal glands and ovaries (pelvic MRI, MSCT of the retroperitoneal space), and genetic testing for CYP21A2 gene mutations, when necessary, to exclude the excessive androgen production or adrenocortical tumorigenesis. In order to identify the source of hyperandrogenism, multisteroid blood analysis may be performed as an additional method using HPLC-MS/MS.

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About the authors

Ksenia V. Ivashchenko

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: kseniya223@mail.ru
ORCID iD: 0000-0002-0786-7809

Endocrinologist, PhD Student

Russian Federation, Moscow

Natalya V. Molashenko

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: molashenko@mail.ru
ORCID iD: 0000-0001-6265-1210
SPIN-code: 5679-2808

PhD, Endocrinologist

Russian Federation, Moscow

Nadezhda M. Platonova

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: doc-platonova@inbox.ru
ORCID iD: 0000-0001-6388-1544
SPIN-code: 4053-3033

Dr. Med. Sci., Professor, Head of the Department of Therapeutic Endocrinology

Russian Federation, Moscow

Anna A. Roslyakova

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: aroslyakova12@gmail.com
ORCID iD: 0000-0003-1857-5083
SPIN-code: 5984-4175

Endocrinologist

Russian Federation, Moscow

Vitaly A. Ioutsi

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: vitalik_org@mail.ru
ORCID iD: 0000-0001-9002-1662
SPIN-code: 9734-0997

PhD, Head of the Laboratory of Metabolomic and Proteomic Studies

Russian Federation, Moscow

Maxim V. Ovcharov

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: ovcharov.maksim@endocrincentr.ru
ORCID iD: 0000-0001-7879-2034
SPIN-code: 6999-1893

PhD, Senior Researcher at the Laboratory of Metabolomic and Proteomic Studies

Russian Federation, Moscow

Maria A. Antsupova

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: masha_ancupova@mail.ru

Researcher at the Laboratory of Metabolomic and Proteomic Studies

Russian Federation, Moscow

Anastasia M. Lapshina

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: anastasya.lapshina@endocrincentr.ru
ORCID iD: 0000-0003-4353-6705

PhD, Pathologist

Russian Federation, Moscow

Svetlana A. Buryakina

National Medical Research Center for Endocrinology, Ministry of Health of Russia

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

PhD, Radiologist

Russian Federation, Moscow

Dmitry G. Beltsevich

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: belts67@gmail.com
ORCID iD: 0000-0001-7098-4584

Dr. Med. Sci., Professor

Russian Federation, Moscow

Nikolay S. Kuznetsov

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: kuznetsov-enc@yandex.ru
ORCID iD: 0000-0002-9419-7013
SPIN-code: 8412-1098

Dr. Med. Sci., Professor

Russian Federation, Moscow

Elena N. Andreeva

National Medical Research Center for Endocrinology, Ministry of Health of Russia; Russian University of Medicine, Ministry of Health of Russia

Email: endogin@mail.ru
ORCID iD: 0000-0001-8425-0020
SPIN-code: 1239-2937

Dr. Med. Sci., Professor, Director of the Institute of Reproductive Medicine

Russian Federation, Moscow; Moscow

Ekaterina A. Troshina

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Email: troshina@inbox.ru
ORCID iD: 0000-0002-8520-8702
SPIN-code: 8821-8990

Dr. Med. Sci., Professor, Corresponding Member of the RAS

Russian Federation, Moscow

Galina A. Melnichenko

National Medical Research Center for Endocrinology, Ministry of Health of Russia

Author for correspondence.
Email: teofrast2000@mail.ru
ORCID iD: 0000-0002-5634-7877
SPIN-code: 8615-0038

Dr. Med. Sci., Professor, Corresponding Member of the RAS, Deputy Director for Scientific Work

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Adrenal MSCT: A. Native phase. B. Arterial phase. В. Venous phase. D. Delayed phase

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3. Fig. 2. Pathomorphological findings of the adrenal gland. Diffuse tumour growth (3.6 cm in size) of the right adrenal gland tissue is determined, mainly of solid structure consisting of large irregularly shaped cells with granular eosinophilic cytoplasm and polymorphic nuclei. There are focal haemorrhages in the thickness of the tumour tissue. No signs of invasion of its own capsule and/or vessels were revealed. Haematoxylin and eosin staining. A - x300. B - x400

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4. Fig. 3. Disorders of synthesis of steroidogenesis enzymes

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