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Макронодулярная двусторонняя гиперплазия надпочечников: патогенез и генетические аспекты
Макронодулярная двусторонняя гиперплазия надпочечников: патогенез и генетические аспекты
Юкина М.Ю., Нуралиева Н.Ф., Бельцевич Д.Г. и др. Макронодулярная двусторонняя гиперплазия надпочечников: патогенез и генетические аспекты. Consilium Medicum. 2016; 18 (1): 88–93. DOI: 10.26442/2075-1753_2016.1.88-93
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Аннотация
Макронодулярная двусторонняя гиперплазия надпочечников (МДГН) – это, в большинстве случаев, генетически детерминированное заболевание, которое проявляется симптомами гиперкортицизма. Диагностика МДГН зачастую представляет сложности в связи с отсутствием типичных клинических проявлений, спорными лабораторными данными, большим количеством и различными диагностическими критериями (cut-off points) тестов, низкой специфичностью при лучевой диагностике.
According to the latest data, a central role in hormonal hypersecretion and cellular proliferation in MBAH play aberrant membrane receptors of adrenal cortex, ectopic adrenocorticotropic hormone production, defects in adenylate cyclase and Wnt signaling systems, disorders of steroidogenesis. However, the exact molecular mechanisms, responsible for the development of MBAH, are unknown. The identification of pathogenetic mechanisms of development MBAH will allow to develop new methods of timely diagnostics and comprehensive treatment of the disease.
Key words: macronodular bilateral adrenal hyperplasia, aberrant membrane receptors, hypercortisolism.
Согласно последним данным, центральную роль в гормональной гиперсекреции и клеточной пролиферации при МДГН играют аберрантно экспрессируемые мембранные рецепторы в коре надпочечников, эктопическая продукция адренокортикотропного гормона, дефекты в аденилатциклазной и Wnt-сигнальных системах, нарушения стероидогенеза. Однако точные молекулярные механизмы, ответственные за развитие МДГН, неизвестны. Идентификация патогенетических механизмов развития МДГН позволит разработать новые методы своевременной диагностики и комплексного лечения заболевания.
Ключевые слова: макронодулярная двусторонняя гиперплазия надпочечников, аберрантные мембранные рецепторы, гиперкортицизм.
Ключевые слова: макронодулярная двусторонняя гиперплазия надпочечников, аберрантные мембранные рецепторы, гиперкортицизм.
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According to the latest data, a central role in hormonal hypersecretion and cellular proliferation in MBAH play aberrant membrane receptors of adrenal cortex, ectopic adrenocorticotropic hormone production, defects in adenylate cyclase and Wnt signaling systems, disorders of steroidogenesis. However, the exact molecular mechanisms, responsible for the development of MBAH, are unknown. The identification of pathogenetic mechanisms of development MBAH will allow to develop new methods of timely diagnostics and comprehensive treatment of the disease.
Key words: macronodular bilateral adrenal hyperplasia, aberrant membrane receptors, hypercortisolism.
Полный текст
Список литературы
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17. Lefebvre H, Duparc С, Chartrel N. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab 2003; 88 (7): 3035–42.
18. Lerario AM, Moraitis A, Hammer GD. Genetics and epigenetics of adrenocortical tumors. Mol Cell Endocrinol 2014; 386 (1–2): 67–84.
19. Stratakis CА, Horvath А. How the new tools to analyze the human genome are opening new perspectives: the use of gene expression in investigations of the adrenal cortex. Ann Endocrinol (Paris) 2008; 69 (2): 123–9.
2. Lacroix A, Costa MHS. Cushing’s Syndrome Secondary to ACTH-Independent Macronodular Adrenal Hyperplasia. Arq Bras Endocrinol Metab 2007; 51 (8): 1226–37.
3. Cavagnini F, Giraldi FP. Adrenal Causes of Cushing’s Syndrome. In: Jameson JL, De Groot LG, editors. Endocrinology: Adult and Pediatric. 7th Edition. 2015; р. 1775–809.
4. Hayakawa E, Yoshimoto T, Hiraishi K. et al. A rare case of ACTH-independent macronodular adrenal hyperplasia associated with aldosterone-producing adenoma. Intern Med 2011; 50 (3): 227–32.
5. Elbelt U, Trovato A, Kloth M. Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. J Clin Endocrinol Metab 2015; 100 (1): E119–28.
6. Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia and aberrant hormone receptors. Horm Res 2005; 64 (3): 119–31.
7. Fragoso MCBV, Alencar GA, Lerario AM. Genetics of primary macronodular adrenal hyperplasia. J Endocrinol 2015; 224 (1): R31–43.
8. Ohashi А, Yamada Y, Sakaguchi K et al. A Natural History of Adrenocorticotropin-Independent Bilateral Adrenal Macronodular Hyperplasia (AIMAH) from Preclinical to Clinically Overt Cushing's Syndrome. Endocrine J 2001; 48: 677–83.
9. Lacroix A. ACTH-independent macronodular adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009; 23 (2): 245–59.
10. Anagnostis P, Karras SN, Athyros VG et al. Subclinical Cushing’s syndrome and cardiovascular disease. Lancet Diabetes Endocrinol 2014; 2 (5): 361.
11. Albiger NM, Occhi G, Mariniello В et al. Food-dependent Cushing’s syndrome: from molecular characterization to therapeutical results. Eur J Endocrinol 2007; 157 (6): 771–8.
12. Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev 2001; 22: 75–110.
13. Lefebvre H, Duparc С, Prévost G. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism. Front Endocrinol (Lausanne) 2015; 6: 34.
14. Bernichtein S, Alevizaki M, Huhtaniemi I. Is the adrenal cortex a target for gonadotropins? Trends Endocrinol Metab 2008; 19 (7): 231–8.
15. Louiset E, Lefebvre H. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. N Engl J Med 2014; 370 (11): 1071–2.
16. Newfield RS. ACTH receptor blockade: a novel approach to treat congenital adrenal hyperplasia, or Cushing’s disease. Med Hypotheses 2010; 74 (4): 705–6.
17. Lefebvre H, Duparc С, Chartrel N. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab 2003; 88 (7): 3035–42.
18. Lerario AM, Moraitis A, Hammer GD. Genetics and epigenetics of adrenocortical tumors. Mol Cell Endocrinol 2014; 386 (1–2): 67–84.
19. Stratakis CА, Horvath А. How the new tools to analyze the human genome are opening new perspectives: the use of gene expression in investigations of the adrenal cortex. Ann Endocrinol (Paris) 2008; 69 (2): 123–9.
2. Lacroix A, Costa MHS. Cushing’s Syndrome Secondary to ACTH-Independent Macronodular Adrenal Hyperplasia. Arq Bras Endocrinol Metab 2007; 51 (8): 1226–37.
3. Cavagnini F, Giraldi FP. Adrenal Causes of Cushing’s Syndrome. In: Jameson JL, De Groot LG, editors. Endocrinology: Adult and Pediatric. 7th Edition. 2015; р. 1775–809.
4. Hayakawa E, Yoshimoto T, Hiraishi K. et al. A rare case of ACTH-independent macronodular adrenal hyperplasia associated with aldosterone-producing adenoma. Intern Med 2011; 50 (3): 227–32.
5. Elbelt U, Trovato A, Kloth M. Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. J Clin Endocrinol Metab 2015; 100 (1): E119–28.
6. Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia and aberrant hormone receptors. Horm Res 2005; 64 (3): 119–31.
7. Fragoso MCBV, Alencar GA, Lerario AM. Genetics of primary macronodular adrenal hyperplasia. J Endocrinol 2015; 224 (1): R31–43.
8. Ohashi А, Yamada Y, Sakaguchi K et al. A Natural History of Adrenocorticotropin-Independent Bilateral Adrenal Macronodular Hyperplasia (AIMAH) from Preclinical to Clinically Overt Cushing's Syndrome. Endocrine J 2001; 48: 677–83.
9. Lacroix A. ACTH-independent macronodular adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009; 23 (2): 245–59.
10. Anagnostis P, Karras SN, Athyros VG et al. Subclinical Cushing’s syndrome and cardiovascular disease. Lancet Diabetes Endocrinol 2014; 2 (5): 361.
11. Albiger NM, Occhi G, Mariniello В et al. Food-dependent Cushing’s syndrome: from molecular characterization to therapeutical results. Eur J Endocrinol 2007; 157 (6): 771–8.
12. Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev 2001; 22: 75–110.
13. Lefebvre H, Duparc С, Prévost G. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism. Front Endocrinol (Lausanne) 2015; 6: 34.
14. Bernichtein S, Alevizaki M, Huhtaniemi I. Is the adrenal cortex a target for gonadotropins? Trends Endocrinol Metab 2008; 19 (7): 231–8.
15. Louiset E, Lefebvre H. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. N Engl J Med 2014; 370 (11): 1071–2.
16. Newfield RS. ACTH receptor blockade: a novel approach to treat congenital adrenal hyperplasia, or Cushing’s disease. Med Hypotheses 2010; 74 (4): 705–6.
17. Lefebvre H, Duparc С, Chartrel N. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab 2003; 88 (7): 3035–42.
18. Lerario AM, Moraitis A, Hammer GD. Genetics and epigenetics of adrenocortical tumors. Mol Cell Endocrinol 2014; 386 (1–2): 67–84.
19. Stratakis CА, Horvath А. How the new tools to analyze the human genome are opening new perspectives: the use of gene expression in investigations of the adrenal cortex. Ann Endocrinol (Paris) 2008; 69 (2): 123–9.
________________________________________________
2. Lacroix A, Costa MHS. Cushing’s Syndrome Secondary to ACTH-Independent Macronodular Adrenal Hyperplasia. Arq Bras Endocrinol Metab 2007; 51 (8): 1226–37.
3. Cavagnini F, Giraldi FP. Adrenal Causes of Cushing’s Syndrome. In: Jameson JL, De Groot LG, editors. Endocrinology: Adult and Pediatric. 7th Edition. 2015; р. 1775–809.
4. Hayakawa E, Yoshimoto T, Hiraishi K. et al. A rare case of ACTH-independent macronodular adrenal hyperplasia associated with aldosterone-producing adenoma. Intern Med 2011; 50 (3): 227–32.
5. Elbelt U, Trovato A, Kloth M. Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. J Clin Endocrinol Metab 2015; 100 (1): E119–28.
6. Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia and aberrant hormone receptors. Horm Res 2005; 64 (3): 119–31.
7. Fragoso MCBV, Alencar GA, Lerario AM. Genetics of primary macronodular adrenal hyperplasia. J Endocrinol 2015; 224 (1): R31–43.
8. Ohashi А, Yamada Y, Sakaguchi K et al. A Natural History of Adrenocorticotropin-Independent Bilateral Adrenal Macronodular Hyperplasia (AIMAH) from Preclinical to Clinically Overt Cushing's Syndrome. Endocrine J 2001; 48: 677–83.
9. Lacroix A. ACTH-independent macronodular adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009; 23 (2): 245–59.
10. Anagnostis P, Karras SN, Athyros VG et al. Subclinical Cushing’s syndrome and cardiovascular disease. Lancet Diabetes Endocrinol 2014; 2 (5): 361.
11. Albiger NM, Occhi G, Mariniello В et al. Food-dependent Cushing’s syndrome: from molecular characterization to therapeutical results. Eur J Endocrinol 2007; 157 (6): 771–8.
12. Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev 2001; 22: 75–110.
13. Lefebvre H, Duparc С, Prévost G. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism. Front Endocrinol (Lausanne) 2015; 6: 34.
14. Bernichtein S, Alevizaki M, Huhtaniemi I. Is the adrenal cortex a target for gonadotropins? Trends Endocrinol Metab 2008; 19 (7): 231–8.
15. Louiset E, Lefebvre H. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. N Engl J Med 2014; 370 (11): 1071–2.
16. Newfield RS. ACTH receptor blockade: a novel approach to treat congenital adrenal hyperplasia, or Cushing’s disease. Med Hypotheses 2010; 74 (4): 705–6.
17. Lefebvre H, Duparc С, Chartrel N. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab 2003; 88 (7): 3035–42.
18. Lerario AM, Moraitis A, Hammer GD. Genetics and epigenetics of adrenocortical tumors. Mol Cell Endocrinol 2014; 386 (1–2): 67–84.
19. Stratakis CА, Horvath А. How the new tools to analyze the human genome are opening new perspectives: the use of gene expression in investigations of the adrenal cortex. Ann Endocrinol (Paris) 2008; 69 (2): 123–9.
Авторы
М.Ю.Юкина*, Н.Ф.Нуралиева, Д.Г.Бельцевич, Е.А.Трошина, Н.М.Платонова
ФГБУ Эндокринологический научный центр Минздрава России. 117036, Россия, Москва, ул. Дмитрия Ульянова, д. 11
*endo-yukina@yandex.ru
Endocrinology Research Center of the Ministry of Health of the Russian Federation. 117036, Russian Federation, Moscow, ul. Dmitria Ul'ianova, d. 11
*endo-yukina@yandex.ru
ФГБУ Эндокринологический научный центр Минздрава России. 117036, Россия, Москва, ул. Дмитрия Ульянова, д. 11
*endo-yukina@yandex.ru
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Endocrinology Research Center of the Ministry of Health of the Russian Federation. 117036, Russian Federation, Moscow, ul. Dmitria Ul'ianova, d. 11
*endo-yukina@yandex.ru
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