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Метод сравнительного селективного забора крови из надпочечниковых вен в дифференциальной диагностике первичного гиперальдостеронизма на примере клинического случая
Метод сравнительного селективного забора крови из надпочечниковых вен в дифференциальной диагностике первичного гиперальдостеронизма на примере клинического случая
Ситкин И.И., Романова Н.Ю., Платонова Н.М. и др. Метод сравнительного селективного забора крови из надпочечниковых вен в дифференциальной диагностике первичного гиперальдостеронизма на примере клинического случая. Consilium Medicum. 2019; 21 (4): 109–113. DOI: 10.26442/20751753.2019.4.190334
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Аннотация
Первичный гиперальдостеронизм (ПГА) является наиболее распространенной причиной эндокринной артериальной гипертензии, встречающейся у 5–10% пациентов с артериальной гипертензией. Получены убедительные доказательства, указывающие, что ПГА повышает риск сердечно-сосудистых осложнений, соответственно, ранняя диагностика и лечение пациентов с определением дальнейшей тактики – ключевой шаг для предотвращения прогрессирования сердечно-сосудистых осложнений. Выбор наиболее подходящего метода лечения для пациентов с ПГА зависит от диагностики нозологических подтипов – двусторонняя гиперплазия надпочечников (также известная как идиопатический гиперальдостеронизм), при которой рекомендован консервативный метод лечения, или односторонний гиперальдостеронизм вследствие альдостеронпродуцирующей аденомы, при которой тактикой выбора является хирургическое лечение (односторонняя адреналэктомия). Кроме того, «очевидные» надпочечниковые аденомы фактически могут оказаться участками очаговой гиперплазии – диагностическая ошибка в этом случае приводит к необоснованному выполнению односторонней адреналэктомии. В целях уточнения латерализации гиперпродукции альдостерона используется сравнительный селективный забор крови из надпочечниковых вен. Однако данный метод дорогостоящий и инвазивный, требует оснащенной рентгеноперационной, квалифицированного эндоваскулярного хирурга и проводится в специализированных центрах. В настоящем клиническом случае мы хотим продемонстрировать важность поэтапной диагностики ПГА.
Ключевые слова: первичный гиперальдостеронизм, гипокалиемия, альдостерон-рениновое соотношение, сравнительный селективный забор из надпочечниковых вен, альдостерома, антагонист минералокортикоидных рецепторов, клинический случай.
Ключевые слова: первичный гиперальдостеронизм, гипокалиемия, альдостерон-рениновое соотношение, сравнительный селективный забор из надпочечниковых вен, альдостерома, антагонист минералокортикоидных рецепторов, клинический случай.
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Primary aldosteronism is the most common cause of endocrine hypertension, occurring in 5–10% of patients with hypertension. Convincing evidence has been obtained indicating that primary aldosteronism increases the risk of cardiovascular complications, respectively, early diagnosis and treatment of patients with the definition of further tactics is a key step to prevent the progression of cardiovascular complications. The choice of the most appropriate treatment method for patients with primary aldosteronism depends on the diagnosis of nosological subtypes – bilateral adrenal hyperplasia (also known as idiopathic aldosteronism), which recommends a conservative treatment or unilateral aldosteronism due to aldosterone-producing adenoma, in which surgical treatment (adrenalectomy) is the tactic of choice. In addition, the "obvious" adrenal adenomas may in fact turn out to be areas of focal hyperplasia – a diagnostic error in this case leads to the unreasonable implementation of adrenalectomy. In order to clarify the lateralization of aldosterone hyperproduction, adrenal venous sampling is used. However, this method requires constant radiography, qualified endovascular surgery and is carried out in centralized medical hospitals. In this clinical case, we want to demonstrate the importance of a diagnosis of primary aldosteronism step by step.
Key words: primary aldosteronism, hypokalemia, aldosterone-renin ratio, adrenal venous sampling, aldosterone-producing adenoma, mineralocorticoid antagonist, clinical case.
Key words: primary aldosteronism, hypokalemia, aldosterone-renin ratio, adrenal venous sampling, aldosterone-producing adenoma, mineralocorticoid antagonist, clinical case.
Полный текст
Список литературы
1. Мельниченко Г.А., Платонова Н.М., Бельцевич Д.Г. и др. Первичный гиперальдостеронизм: диагностика и лечение. Новый взгляд на проблему. По материалам Проекта клинических рекомендаций Российской ассоциации эндокринологов по диагностике и лечению первичного гиперальдостеронизма. Consilium Medicum. 2017; 19 (4): 75-85.
[Melnichenko G.A., Platonova N.M., Beltsevich D.G. et al. Primary hyperaldosteronism: diagnosis and treatment. A new look at the problem. According to the materials of the Russian Association of Endocrinologists clinical guidelines for primary hyperaldosteronism diagnosis and treatment Consilium Medicum. 2017; 19 (4): 75–85 (in Russian).]
2. Mancia GI, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
3. Mulatero P, Bertello C, Sukor N et al. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension 2010; 55: 667–73.
4. Ladurner K, Hallfeldt J, Id O et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest 2017; 47: 372–7.
5. Haase M, Riester A, Kropil P et al. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab 2014; 99: 4397–402.
6. Omura K, Ota H, Takahashi Y et al. Anatomical variations of the right adrenal vein. Hypertension 2017; 69: 428–34.
7. Rossi GP, Auchus RJ, Brown M et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 64: 151–60.
8. Miotto D, De Toni R, Pitter G et al. Impact of accessory hepatic veins on adrenal vein sampling for identification of surgically curable primary aldosteronism. Hypertension 2009; 54: 885–9.
9. Dekkers T, Prejbisz A, Kool LJ et al. Investigators S. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcomebased randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739–46.
10. Cesari M, Ceolotto G, Rossitto G et al. The intra-procedural cortisol assay during adrenal vein sampling: rationale and design of a randomized study (IPadua). High Blood Press Cardiovasc Prev 2017; 24: 167–70.
11. Fischer E, Hanslik G, Pallauf A et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97: 3965–73.
12. Rossi GP. Update in adrenal venous sampling for primary aldosteronism. Current Opinion in endocrinology, diabetes, and obesity 2018; 25 (3): 160–71.
13. Yoneda T, Karashima S, Kometani M et al. Impact of new quick gold nanoparticle-based cortisol assay during adrenal vein sampling for primary aldosteronism. J Clin Endocrinol Metab 2016; 101: 2554–61.
14. Rossitto G, Battistel M, Barbiero G et al. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization. J Hypertens 2018; 36: 335–43.
15. Marlies JE, Kempers MD, Jacques WM et al. Systematic Review: Diagnostic Proceduresto Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Ann Intern Med 2009; 151. Issue 5; p. 329–37.
16. Rossi GP, Barisa M, Allolio et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97 (5): 1606–14.
17. Funder JW, Carey RM, Fardella C et al. An Endocrine Society Clinical Practice Guidelines. Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101 (5): 1889–916.
18. Sarlon-Bartoli G, Michel N, Taieb D et al. Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography. J Hypertens 2011; 29: 1196–202.
19. Lim V, Guo Q, Grant CS et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712–9.
20. Rossi E, Regolisti G, Perazzoli F et al. Intraprocedural cortisol measurement increases adrenal vein sampling success rate in primary aldosteronism. Am J Hypertens 2011; 24: 1280–5.
21. Auchus RJ, Michaelis C, Wians FH et al. Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg 2009; 249: 318–21.
22. Покровский А.В., Торгунаков А.П., Торгунаков С.А. Многолетнее наблюдение за пациентами после односторонней портализации надпочечниковой и почечной крови при первичном гиперальдостеронизме. Хирургия. 2009; 3: 65–6.
[Pokrovskii A.V., Torgunakov A.P., Torgunakov S.A. Mnogoletnee nabliudenie za patsientami posle odnostoronnei portalizatsii nadpochechnikovoi i pochechnoi krovi pri pervichnom giperal'dosteronizme. Khirurgiia. 2009; 3: 65–6 (in Russian).]
2. Mancia GI, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
3. Mulatero P, Bertello C, Sukor N et al. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension 2010; 55: 667–73.
4. Ladurner K, Hallfeldt J, Id O et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest 2017; 47: 372–7.
5. Haase M, Riester A, Kropil P et al. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab 2014; 99: 4397–402.
6. Omura K, Ota H, Takahashi Y et al. Anatomical variations of the right adrenal vein. Hypertension 2017; 69: 428–34.
7. Rossi GP, Auchus RJ, Brown M et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 64: 151–60.
8. Miotto D, De Toni R, Pitter G et al. Impact of accessory hepatic veins on adrenal vein sampling for identification of surgically curable primary aldosteronism. Hypertension 2009; 54: 885–9.
9. Dekkers T, Prejbisz A, Kool LJ et al. Investigators S. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcomebased randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739–46.
10. Cesari M, Ceolotto G, Rossitto G et al. The intra-procedural cortisol assay during adrenal vein sampling: rationale and design of a randomized study (IPadua). High Blood Press Cardiovasc Prev 2017; 24: 167–70.
11. Fischer E, Hanslik G, Pallauf A et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97: 3965–73.
12. Rossi GP. Update in adrenal venous sampling for primary aldosteronism. Current Opinion in endocrinology, diabetes, and obesity 2018; 25 (3): 160–71.
13. Yoneda T, Karashima S, Kometani M et al. Impact of new quick gold nanoparticle-based cortisol assay during adrenal vein sampling for primary aldosteronism. J Clin Endocrinol Metab 2016; 101: 2554–61.
14. Rossitto G, Battistel M, Barbiero G et al. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization. J Hypertens 2018; 36: 335–43.
15. Marlies JE, Kempers MD, Jacques WM et al. Systematic Review: Diagnostic Proceduresto Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Ann Intern Med 2009; 151. Issue 5; p. 329–37.
16. Rossi GP, Barisa M, Allolio et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97 (5): 1606–14.
17. Funder JW, Carey RM, Fardella C et al. An Endocrine Society Clinical Practice Guidelines. Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101 (5): 1889–916.
18. Sarlon-Bartoli G, Michel N, Taieb D et al. Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography. J Hypertens 2011; 29: 1196–202.
19. Lim V, Guo Q, Grant CS et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712–9.
20. Rossi E, Regolisti G, Perazzoli F et al. Intraprocedural cortisol measurement increases adrenal vein sampling success rate in primary aldosteronism. Am J Hypertens 2011; 24: 1280–5.
21. Auchus RJ, Michaelis C, Wians FH et al. Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg 2009; 249: 318–21.
22. Pokrovskii A.V., Torgunakov A.P., Torgunakov S.A. Mnogoletnee nabliudenie za patsientami posle odnostoronnei portalizatsii nadpochechnikovoi i pochechnoi krovi pri pervichnom giperal'dosteronizme. Khirurgiia. 2009; 3: 65–6 (in Russian).
[Melnichenko G.A., Platonova N.M., Beltsevich D.G. et al. Primary hyperaldosteronism: diagnosis and treatment. A new look at the problem. According to the materials of the Russian Association of Endocrinologists clinical guidelines for primary hyperaldosteronism diagnosis and treatment Consilium Medicum. 2017; 19 (4): 75–85 (in Russian).]
2. Mancia GI, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
3. Mulatero P, Bertello C, Sukor N et al. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension 2010; 55: 667–73.
4. Ladurner K, Hallfeldt J, Id O et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest 2017; 47: 372–7.
5. Haase M, Riester A, Kropil P et al. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab 2014; 99: 4397–402.
6. Omura K, Ota H, Takahashi Y et al. Anatomical variations of the right adrenal vein. Hypertension 2017; 69: 428–34.
7. Rossi GP, Auchus RJ, Brown M et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 64: 151–60.
8. Miotto D, De Toni R, Pitter G et al. Impact of accessory hepatic veins on adrenal vein sampling for identification of surgically curable primary aldosteronism. Hypertension 2009; 54: 885–9.
9. Dekkers T, Prejbisz A, Kool LJ et al. Investigators S. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcomebased randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739–46.
10. Cesari M, Ceolotto G, Rossitto G et al. The intra-procedural cortisol assay during adrenal vein sampling: rationale and design of a randomized study (IPadua). High Blood Press Cardiovasc Prev 2017; 24: 167–70.
11. Fischer E, Hanslik G, Pallauf A et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97: 3965–73.
12. Rossi GP. Update in adrenal venous sampling for primary aldosteronism. Current Opinion in endocrinology, diabetes, and obesity 2018; 25 (3): 160–71.
13. Yoneda T, Karashima S, Kometani M et al. Impact of new quick gold nanoparticle-based cortisol assay during adrenal vein sampling for primary aldosteronism. J Clin Endocrinol Metab 2016; 101: 2554–61.
14. Rossitto G, Battistel M, Barbiero G et al. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization. J Hypertens 2018; 36: 335–43.
15. Marlies JE, Kempers MD, Jacques WM et al. Systematic Review: Diagnostic Proceduresto Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Ann Intern Med 2009; 151. Issue 5; p. 329–37.
16. Rossi GP, Barisa M, Allolio et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97 (5): 1606–14.
17. Funder JW, Carey RM, Fardella C et al. An Endocrine Society Clinical Practice Guidelines. Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101 (5): 1889–916.
18. Sarlon-Bartoli G, Michel N, Taieb D et al. Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography. J Hypertens 2011; 29: 1196–202.
19. Lim V, Guo Q, Grant CS et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712–9.
20. Rossi E, Regolisti G, Perazzoli F et al. Intraprocedural cortisol measurement increases adrenal vein sampling success rate in primary aldosteronism. Am J Hypertens 2011; 24: 1280–5.
21. Auchus RJ, Michaelis C, Wians FH et al. Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg 2009; 249: 318–21.
22. Покровский А.В., Торгунаков А.П., Торгунаков С.А. Многолетнее наблюдение за пациентами после односторонней портализации надпочечниковой и почечной крови при первичном гиперальдостеронизме. Хирургия. 2009; 3: 65–6.
[Pokrovskii A.V., Torgunakov A.P., Torgunakov S.A. Mnogoletnee nabliudenie za patsientami posle odnostoronnei portalizatsii nadpochechnikovoi i pochechnoi krovi pri pervichnom giperal'dosteronizme. Khirurgiia. 2009; 3: 65–6 (in Russian).]
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2. Mancia GI, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
3. Mulatero P, Bertello C, Sukor N et al. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension 2010; 55: 667–73.
4. Ladurner K, Hallfeldt J, Id O et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest 2017; 47: 372–7.
5. Haase M, Riester A, Kropil P et al. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab 2014; 99: 4397–402.
6. Omura K, Ota H, Takahashi Y et al. Anatomical variations of the right adrenal vein. Hypertension 2017; 69: 428–34.
7. Rossi GP, Auchus RJ, Brown M et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 64: 151–60.
8. Miotto D, De Toni R, Pitter G et al. Impact of accessory hepatic veins on adrenal vein sampling for identification of surgically curable primary aldosteronism. Hypertension 2009; 54: 885–9.
9. Dekkers T, Prejbisz A, Kool LJ et al. Investigators S. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcomebased randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739–46.
10. Cesari M, Ceolotto G, Rossitto G et al. The intra-procedural cortisol assay during adrenal vein sampling: rationale and design of a randomized study (IPadua). High Blood Press Cardiovasc Prev 2017; 24: 167–70.
11. Fischer E, Hanslik G, Pallauf A et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97: 3965–73.
12. Rossi GP. Update in adrenal venous sampling for primary aldosteronism. Current Opinion in endocrinology, diabetes, and obesity 2018; 25 (3): 160–71.
13. Yoneda T, Karashima S, Kometani M et al. Impact of new quick gold nanoparticle-based cortisol assay during adrenal vein sampling for primary aldosteronism. J Clin Endocrinol Metab 2016; 101: 2554–61.
14. Rossitto G, Battistel M, Barbiero G et al. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization. J Hypertens 2018; 36: 335–43.
15. Marlies JE, Kempers MD, Jacques WM et al. Systematic Review: Diagnostic Proceduresto Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Ann Intern Med 2009; 151. Issue 5; p. 329–37.
16. Rossi GP, Barisa M, Allolio et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97 (5): 1606–14.
17. Funder JW, Carey RM, Fardella C et al. An Endocrine Society Clinical Practice Guidelines. Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101 (5): 1889–916.
18. Sarlon-Bartoli G, Michel N, Taieb D et al. Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography. J Hypertens 2011; 29: 1196–202.
19. Lim V, Guo Q, Grant CS et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712–9.
20. Rossi E, Regolisti G, Perazzoli F et al. Intraprocedural cortisol measurement increases adrenal vein sampling success rate in primary aldosteronism. Am J Hypertens 2011; 24: 1280–5.
21. Auchus RJ, Michaelis C, Wians FH et al. Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg 2009; 249: 318–21.
22. Pokrovskii A.V., Torgunakov A.P., Torgunakov S.A. Mnogoletnee nabliudenie za patsientami posle odnostoronnei portalizatsii nadpochechnikovoi i pochechnoi krovi pri pervichnom giperal'dosteronizme. Khirurgiia. 2009; 3: 65–6 (in Russian).
Авторы
И.И.Ситкин, Н.Ю.Романова*, Н.М.Платонова, Н.В.Молашенко, Е.А.Трошина
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
*natasharomanova1991@gmail.com
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
*natasharomanova1991@gmail.com
________________________________________________
Ivan I. Sitkin, Natalia Yu. Romanova*, Nadezhda M. Platonova, Natalya V. Molashenko, Ekaterina A. Troshina
Endocrinology Research Centre, Moscow, Russia
*natasharomanova1991@gmail.com
Endocrinology Research Centre, Moscow, Russia
*natasharomanova1991@gmail.com
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