Адренокортикальный рак: поздняя диагностика заболевания на примере клинического случая - Журнал Терапевтический архив №12 Vario 2023

Адренокортикальный рак: поздняя диагностика заболевания на примере клинического случая

Старостина Е.А., Молашенко Н.В., Левшина А.Р., Пачуашвили Н.В., Шевэ А., Исаева М.П., Гетажеев К.В., Бельцевич Д.Г., Платонова Н.М., Трошина Е.А. Адренокортикальный рак: поздняя диагностика заболевания на примере клинического случая. Терапевтический архив. 2023;95(12):1179–1184.
DOI: 10.26442/00403660.2023.12.202430

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

________________________________________________

Starostina EA, Molashenko NV, Levshina AR, Pachuashvili NV, Chevais A, Isaeva MP, Getazheev KV, Beltsevich DG, Platonova NM, Troshina EA. Adrenocortical cancer: late diagnosis of the disease on the example of a clinical case. Case report. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(12):1179–1184.
DOI: 10.26442/00403660.2023.12.202430

Читать PDF

Аннотация

Адренокортикальный рак (АКР) – редкая злокачественная опухоль коры надпочечников c распространенностью 0,5–2 случая на 1 млн населения, характеризующаяся неблагоприятным прогнозом, низкой 5-летней выживаемостью пациентов, поздним сроком выявления и агрессивностью клинического течения. Заболевание чаще встречается среди женщин (1,5:1 или 55–60%), средний возраст на момент постановки диагноза – 40–50 лет. Клинические проявления АКР в большинстве случаев отсутствуют, что является причиной поздней диагностики заболевания. В некоторых случаях АКР диагностируется при рецидиве заболевания после хирургического лечения гормонально-неактивной опухоли надпочечника или на этапе метастазирования. АКР может быть гормонально-активной опухолью, являясь причиной гиперкортицизма/вирильного синдрома и др. Канцерогенез АКР обусловлен как спонтанно возникающими мутациями в соматических клетках коры надпочечников, так и генетическими поломками в рамках того или иного наследственного синдрома, например Ли–Фраумени и Вермера (синдром множественных эндокринных неоплазий 1-го типа). В статье приведен клинический случай, иллюстрирующий последствия поздней диагностики АКР у женщины 46 лет, которая обратилась за медицинской помощью через 1,5 года после развития манифестных симптомов с клиникой вирильного синдрома в сочетании с артериальной гипертензией, инвазией левой почечной вены и распространением опухолевого тромба в просвет нижней полой вены по данным мультиспиральной компьютерной томографии. Данный клинический случай подчеркивает важность онконастороженности и своевременной диагностики АКР с помощью лабораторно-инструментальных и генетических методов.

Ключевые слова: адренокортикальный рак, гиперкортицизм, синдром Иценко–Кушинга, вирильный синдром, митотан

________________________________________________

Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2–4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li–Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.

Keywords: adrenocortical carcinoma, Cushing’s syndrome, hyperandrogenemia, mitotane

Полный текст

Материалы доступны только для специалистов сферы здравоохранения.
Чтобы посмотреть материал полностью Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Schteingart DE, Doherty GM, Gauger PG, et al. Management of patients with adrenal cancer: recommendations of an international consensus conference. Endocr Relat Cancer. 2005;12(3):667-80. DOI:10.1677/erc.1.01029
2. Kerkhofs TMA, Verhoeven RHA, Van der Zwan JM, et al. Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer. 2013;49(11):2579-86. DOI:10.1016/j.ejca.2013.02.034
3. Fassnacht M, Kroiss M, Allolio B. Update in Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2013;98(12):4551-64. DOI:10.1210/jc.2013-3020
4. Lloyd RV, Osamura RY, Klöppel G, Rosai JE. WHO Classification of Tumours of Endocrine Organs. 4th ed., 2017.
5. Sidhu S, Marsh DJ, Theodosopoulos G, et al. Comparative Genomic Hybridization Analysis of Adrenocortical Tumors. J Clin Endocrinol Metab. 2002;87(7):3467-74. DOI:10.1210/jcem.87.7.8697
6. Barreau O, de Reynies A, Wilmot-Roussel H, et al. Clinical and Pathophysiological Implications of Chromosomal Alterations in Adrenocortical Tumors: An Integrated Genomic Approach. J Clin Endocrinol Metab. 2012;97(2):E301-11. DOI:10.1210/jc.2011-1588
7. Assié G, Letouzé E, Fassnacht M, et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014;46(6):607-12. DOI:10.1038/ng.2953
8. Juhlin CC, Goh G, Healy JM, et al. Whole-Exome Sequencing Characterizes the Landscape of Somatic Mutations and Copy Number Alterations in Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2015;100(3):E493-502. DOI:10.1210/jc.2014-3282
9. Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994;78(3):790-4. DOI:10.1210/jcem.78.3.8126158
10. Libè R, Groussin L, Tissier F, et al. Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. Clin Cancer Res. 2007;13(3):844-50. DOI:10.1158/1078-0432.CCR-06-2085
11. Wasserman JD, Zambetti GP, Malkin D. Towards an understanding of the role of p53 in adrenocortical carcinogenesis. Mol Cell Endocrinol. 2012;351(1):101-10. DOI:10.1016/j.mce.2011.09.010
12. Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States. Cancer. 2008;113(11):3130-6. DOI:10.1002/cncr.23886
13. Мельниченко Г.А., Стилиди И.С., Алексеев Б.Я., и др. Федеральные клинические рекомендации по диагностике и лечению адренокортикального рака. Проблемы эндокринологии. 2014;60(2):51-67 [Melnichenko GA, Stilidi IS, Alekseev BYa, et al. Federal clinical practice guidelines on the diagnostics and treatment of adrenocortical cancer. Problems of Endocrinology. 2014;60(2):51-67 (in Russian)].
14. Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(2):273-89. DOI:10.1016/j.beem.2008.10.008
15. Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006;91(6):2027-37. DOI:10.1210/jc.2005-2639
16. Pacak K. Preoperative Management of the Pheochromocytoma Patient. J Clin Endocrinol Metab. 2007;92(11):4069-79. DOI:10.1210/jc.2007-1720
17. Kinney MAO, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth. 2002;16(3):359-69. DOI:10.1053/jcan.2002.124150
18. Nieman LK. Approach to the Patient with an Adrenal Incidentaloma. J Clin Endocrinol Metab. 2010;95(9):4106-13. DOI:10.1210/jc.2010-0457
19. Sturgeon C, Shen WT, Clark OH, et al. Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy? J Am Coll Surg. 2006;202(3):423-30. DOI:10.1016/j.jamcollsurg.2005.11.005
20. Petersenn S, Richter PA, Broemel T, et al. Computed tomography criteria for discrimination of adrenal adenomas and adrenocortical carcinomas: analysis of the German ACC registry. Eur J Endocrinol. 2015;172(4):415-22. DOI:10.1530/EJE-14-0916
21. Angeli A, Osella G, Ali A, Terzolo M. Adrenal Incidentaloma: An Overview of Clinical and Epidemiological Data from the National Italian Study Group. Hormones. 1997;47(4-6):279-83. DOI:10.1159/000185477
22. Metser U, Miller E, Lerman H, et al. 18F-FDG PET/CT in the evaluation of adrenal masses. J Nucl Med. 2006;47(1):32-7.
23. Mackie GC, Shulkin BL, Ribeiro RC, et al. Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. J Clin Endocrinol Metab. 2006;91(7):2665-71. DOI:10.1210/jc.2005-2612
24. Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. J Clin Endocrinol Metab. 2006;91(3):920-5. DOI:10.1210/jc.2005-1540
25. Creemers SG, Hofland LJ, Korpershoek E, et al. Future directions in the diagnosis and medical treatment of adrenocortical carcinoma. Endocr Relat Cancer. 2016;23(1):R43-69. DOI:10.1530/ERC-15-0452
26. Livhits M, Li N, Yeh MW, Harari A. Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease. Surgery. 2014;156(6):1531. DOI:10.1016/j.surg.2014.08.047
27. Hahner S, Fassnacht M. Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs. 2005;6(4):386-94.
28. Puglisi S, Calabrese A, Basile V, et al. New perspectives for mitotane treatment of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2020;34(3):101415. DOI:10.1016/j.beem.2020.101415
29. Bellantone R, Ferrante A, Boscherini M, et al. Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma. Surgery. 1997;122(6):1212-8. DOI:10.1016/s0039-6060(97)90229-4
30. Allolio B, Fassnacht M. Adrenocortical Carcinoma: Clinical Update. J Clin Endocrinol Metab. 2006;91(6):2027-37. DOI:10.1210/jc.2005-2639
31. Grubbs EG, Callender GG, Xing Y, et al. Recurrence of Adrenal Cortical Carcinoma Following Resection: Surgery Alone Can Achieve Results Equal to Surgery Plus Mitotane. Ann Surg Oncol. 2010;17(1):263-70. DOI:10.1245/s10434-009-0716-x
32. Fassnacht M, Johanssen S, Quinkler M, et al. Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma. Cancer. 2009;115(2):243-50. DOI:10.1002/cncr.24030
33. Libé R, Borget I, Ronchi CL, et al. Prognostic factors in stage III–IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study. Ann Oncol. 2015;26(10):2119-25. DOI:10.1093/annonc/mdv329
34. Margonis G, Kim Y, Tran T, et al. Outcomes Following Resection of Cortisol-secreting Adrenocortical Carcinoma. Am J Surg. 2015;211. DOI:10.1016/j.amjsurg.2015.09.020
35. Terzolo M, Berruti A. Adjunctive treatment of adrenocortical carcinoma. Curr Opin Endocrinol Diabetes Obes. 2008;15(3):221-6. DOI:10.1097/MED.0b013e3282fdf4c0
36. Terzolo M, Baudin AE, Ardito A, et al. Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. Eur J Endocrinol. 2013;169(3):263-70. DOI:10.1530/EJE-13-0242
37. Nader N, Raverot G, Emptoz-Bonneton A, et al. Mitotane Has an Estrogenic Effect on Sex Hormone-Binding Globulin and Corticosteroid-Binding Globulin in Humans. J Clin Endocrinol Metab. 2006;91(6):2165-70. DOI:10.1210/jc.2005-2157
38. Kroiss M, Quinkler M, Lutz WK, et al. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75(5):585-91. DOI:10.1111/j.1365-2265.2011.04214.x
39. Berruti A, Grisanti S, Pulzer A, et al. Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2017;102(4):1358-65. DOI:10.1210/jc.2016-2894
40. Fassnacht M, Terzolo M, Allolio B, et al. Combination Chemotherapy in Advanced Adrenocortical Carcinoma. N Engl J Med. 2012;366(23):2189-97. DOI:10.1056/NEJMoa1200966

________________________________________________

1. Schteingart DE, Doherty GM, Gauger PG, et al. Management of patients with adrenal cancer: recommendations of an international consensus conference. Endocr Relat Cancer. 2005;12(3):667-80. DOI:10.1677/erc.1.01029
2. Kerkhofs TMA, Verhoeven RHA, Van der Zwan JM, et al. Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer. 2013;49(11):2579-86. DOI:10.1016/j.ejca.2013.02.034
3. Fassnacht M, Kroiss M, Allolio B. Update in Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2013;98(12):4551-64. DOI:10.1210/jc.2013-3020
4. Lloyd RV, Osamura RY, Klöppel G, Rosai JE. WHO Classification of Tumours of Endocrine Organs. 4th ed., 2017.
5. Sidhu S, Marsh DJ, Theodosopoulos G, et al. Comparative Genomic Hybridization Analysis of Adrenocortical Tumors. J Clin Endocrinol Metab. 2002;87(7):3467-74. DOI:10.1210/jcem.87.7.8697
6. Barreau O, de Reynies A, Wilmot-Roussel H, et al. Clinical and Pathophysiological Implications of Chromosomal Alterations in Adrenocortical Tumors: An Integrated Genomic Approach. J Clin Endocrinol Metab. 2012;97(2):E301-11. DOI:10.1210/jc.2011-1588
7. Assié G, Letouzé E, Fassnacht M, et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014;46(6):607-12. DOI:10.1038/ng.2953
8. Juhlin CC, Goh G, Healy JM, et al. Whole-Exome Sequencing Characterizes the Landscape of Somatic Mutations and Copy Number Alterations in Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2015;100(3):E493-502. DOI:10.1210/jc.2014-3282
9. Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994;78(3):790-4. DOI:10.1210/jcem.78.3.8126158
10. Libè R, Groussin L, Tissier F, et al. Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. Clin Cancer Res. 2007;13(3):844-50. DOI:10.1158/1078-0432.CCR-06-2085
11. Wasserman JD, Zambetti GP, Malkin D. Towards an understanding of the role of p53 in adrenocortical carcinogenesis. Mol Cell Endocrinol. 2012;351(1):101-10. DOI:10.1016/j.mce.2011.09.010
12. Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States. Cancer. 2008;113(11):3130-6. DOI:10.1002/cncr.23886
13. Melnichenko GA, Stilidi IS, Alekseev BYa, et al. Federal clinical practice guidelines on the diagnostics and treatment of adrenocortical cancer. Problems of Endocrinology. 2014;60(2):51-67 (in Russian).
14. Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(2):273-89. DOI:10.1016/j.beem.2008.10.008
15. Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006;91(6):2027-37. DOI:10.1210/jc.2005-2639
16. Pacak K. Preoperative Management of the Pheochromocytoma Patient. J Clin Endocrinol Metab. 2007;92(11):4069-79. DOI:10.1210/jc.2007-1720
17. Kinney MAO, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth. 2002;16(3):359-69. DOI:10.1053/jcan.2002.124150
18. Nieman LK. Approach to the Patient with an Adrenal Incidentaloma. J Clin Endocrinol Metab. 2010;95(9):4106-13. DOI:10.1210/jc.2010-0457
19. Sturgeon C, Shen WT, Clark OH, et al. Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy? J Am Coll Surg. 2006;202(3):423-30. DOI:10.1016/j.jamcollsurg.2005.11.005
20. Petersenn S, Richter PA, Broemel T, et al. Computed tomography criteria for discrimination of adrenal adenomas and adrenocortical carcinomas: analysis of the German ACC registry. Eur J Endocrinol. 2015;172(4):415-22. DOI:10.1530/EJE-14-0916
21. Angeli A, Osella G, Ali A, Terzolo M. Adrenal Incidentaloma: An Overview of Clinical and Epidemiological Data from the National Italian Study Group. Hormones. 1997;47(4-6):279-83. DOI:10.1159/000185477
22. Metser U, Miller E, Lerman H, et al. 18F-FDG PET/CT in the evaluation of adrenal masses. J Nucl Med. 2006;47(1):32-7.
23. Mackie GC, Shulkin BL, Ribeiro RC, et al. Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. J Clin Endocrinol Metab. 2006;91(7):2665-71. DOI:10.1210/jc.2005-2612
24. Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. J Clin Endocrinol Metab. 2006;91(3):920-5. DOI:10.1210/jc.2005-1540
25. Creemers SG, Hofland LJ, Korpershoek E, et al. Future directions in the diagnosis and medical treatment of adrenocortical carcinoma. Endocr Relat Cancer. 2016;23(1):R43-69. DOI:10.1530/ERC-15-0452
26. Livhits M, Li N, Yeh MW, Harari A. Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease. Surgery. 2014;156(6):1531. DOI:10.1016/j.surg.2014.08.047
27. Hahner S, Fassnacht M. Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs. 2005;6(4):386-94.
28. Puglisi S, Calabrese A, Basile V, et al. New perspectives for mitotane treatment of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2020;34(3):101415. DOI:10.1016/j.beem.2020.101415
29. Bellantone R, Ferrante A, Boscherini M, et al. Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma. Surgery. 1997;122(6):1212-8. DOI:10.1016/s0039-6060(97)90229-4
30. Allolio B, Fassnacht M. Adrenocortical Carcinoma: Clinical Update. J Clin Endocrinol Metab. 2006;91(6):2027-37. DOI:10.1210/jc.2005-2639
31. Grubbs EG, Callender GG, Xing Y, et al. Recurrence of Adrenal Cortical Carcinoma Following Resection: Surgery Alone Can Achieve Results Equal to Surgery Plus Mitotane. Ann Surg Oncol. 2010;17(1):263-70. DOI:10.1245/s10434-009-0716-x
32. Fassnacht M, Johanssen S, Quinkler M, et al. Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma. Cancer. 2009;115(2):243-50. DOI:10.1002/cncr.24030
33. Libé R, Borget I, Ronchi CL, et al. Prognostic factors in stage III–IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study. Ann Oncol. 2015;26(10):2119-25. DOI:10.1093/annonc/mdv329
34. Margonis G, Kim Y, Tran T, et al. Outcomes Following Resection of Cortisol-secreting Adrenocortical Carcinoma. Am J Surg. 2015;211. DOI:10.1016/j.amjsurg.2015.09.020
35. Terzolo M, Berruti A. Adjunctive treatment of adrenocortical carcinoma. Curr Opin Endocrinol Diabetes Obes. 2008;15(3):221-6. DOI:10.1097/MED.0b013e3282fdf4c0
36. Terzolo M, Baudin AE, Ardito A, et al. Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. Eur J Endocrinol. 2013;169(3):263-70. DOI:10.1530/EJE-13-0242
37. Nader N, Raverot G, Emptoz-Bonneton A, et al. Mitotane Has an Estrogenic Effect on Sex Hormone-Binding Globulin and Corticosteroid-Binding Globulin in Humans. J Clin Endocrinol Metab. 2006;91(6):2165-70. DOI:10.1210/jc.2005-2157
38. Kroiss M, Quinkler M, Lutz WK, et al. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75(5):585-91. DOI:10.1111/j.1365-2265.2011.04214.x
39. Berruti A, Grisanti S, Pulzer A, et al. Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2017;102(4):1358-65. DOI:10.1210/jc.2016-2894
40. Fassnacht M, Terzolo M, Allolio B, et al. Combination Chemotherapy in Advanced Adren

Авторы

Е.А. Старостина*¹, Н.В. Молашенко¹, А.Р. Левшина², Н.В. Пачуашвили^1,2, А. Шевэ¹, М.П. Исаева¹, К.В. Гетажеев³, Д.Г. Бельцевич¹, Н.М. Платонова¹, Е.А. Трошина¹

¹ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия;
²ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
³ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*colpakova.ev@mail.ru

________________________________________________

Evgenia A. Starostina*¹, Natalya V. Molashenko¹, Anna R. Levshina², Nano V. Pachuashvili^1,2, Anastassia Chevais¹, Mariya P. Isaeva¹, Kantemir V. Getazheev³, Dmitry G. Beltsevich¹, Nadezhda M. Platonova¹, Ekaterina A. Troshina¹

¹Endocrinology Research Centre, Moscow, Russia;
²Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
³Pirogov Russian National Research Medical University, Moscow, Russia
*colpakova.ev@mail.ru

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.