Первичный гиперальдостеронизм: существующие вопросы и возможности решения


DOI: https://dx.doi.org/10.18565/pharmateca.2024.2.8-17

Ладыгина Д.О., Вастистова А.А., Шиленкова Е.С., Платонова Н.М., Бельцевич Д.Г., Фадеев В.В.

1) Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет), Москва, Россия; 2) Национальный медицинский исследовательский центр эндокринологии, Москва, Россия
На долю первичного гиперальдостеронизма (ПГА) как самой частой причины вторичной артериальной гипертензии (АГ), по данным литературы, приходится 10–15% случаев. Однако истинная распространенность ПГА недооценена в связи с отсутствием четких, понятных алгоритмов диагностики для врачей первичного звена, некорректной интерпретацией результатов. В особенности это касается «мягких» форм заболевания. Несмотря на отсутствие яркой клинической картины, ПГА ассоциирован с более высоким риском развития неблагоприятных сердечно-сосудистых событий и метаболических нарушений по сравнению с эссенциальной АГ даже при достижении целевых показателей артериального давления. Понимание новых патогенетических аспектов ПГА, в частности связи между клинической формой заболевания и соматическими мутациями ионных каналов, накапливающихся с возрастом, призвано сделать диагностику ПГА более удобной для повседневной клинической практики, таким образом повысить эффективность лечения и качество жизни пациентов.

Литература


1. Forouzanfar M.H., Alexander L., Anderson H.R.,et al. GBD 2013 Risk factors collaborators global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;386(10010):2287–323. Doi: 10.1016/S0140-6736(15)00128-2.


2. Sukor N. Endocrine hypertension – current understanding and comprehensive management review. Eur J Intern Med. 2011;22(5):433–40. Doi: 10.1016/j.ejim.2011.05.004.


3. Mullen N., Curneen J, Donlon P.T., et al. Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks. Endocr Rev. 2024;45(1):125–70. Doi: 10.1210/endrev/bnad026.


4. Monticone S., D’Ascenzo F., Moretti C., et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet. Diab Endocrinol. 2018;6(1):41–50. Doi: 10.1016/S2213-8587(17)30319-4.


5. Monticone S., Sconfienza E., D’Ascenzo F., et al. Renal damage in primary aldosteronism: a systematic review and meta-analysis. J Hypertens. 2020;38(1):3–12. Doi: 10.1097/HJH.0000000000002216.


6. Vaidya A., Brown J.M., Carey R.M., et al. The Unrecognized Prevalence of Primary Aldosteronism. Ann Intern Med. 2020;173(8):683. Doi: 10.7326/L20-1097.


7. Azizan E.A., Poulsen H., Tuluc P., et al. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet. 2013;45:1055–60. Doi: 10.1038/ng.2716.


8. Gomez-Sanchez C.E., Gomez-Sanchez E.P., Nishimoto K. Immunohistochemistry of the Human Adrenal CYP11B2 in Normal Individuals and in Patients with Primary Aldosteronism. Horm Metab Res. 2020;52(6):421–26. Doi: 10.1055/a-1139-2079.


9. Lim J.S., Rainey W.E. The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease. Horm Metab Res. 2020;52(6):427-34. Doi: 10.1055/a-1128-0421.


10. Rossi G.P., Bernini G., Caliumi C., et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48(11):2293–300. Doi: 10.1016/j.jacc.2006.07.059.


11. Milliez P., Girerd X., Plouin P.F., et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243–48. Doi: 10.1016/j.jacc.2005.01.015.


12. Ohno Y., Sone M., Inagaki N., et al. Prevalence of cardiovascular disease and its risk factors in primary aldosteronism: a multicenter study in Japan. Hypertension. 2018;71(3):530–37. Doi: 10.1161/HYPERTENSIONAHA.117.10263.


13. Rossi G.P. Prevalence and diagnosis of primary aldosteronism. Curr Hypertens Rep. 2010;12(5):342–48. Doi: 10.1007/s11906-010-0134-2.


14. Monticone S., Burrello J., Tizzani D., et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69(14):1811–20. Doi: 10.1016/j.jacc.2017.01.052.


15. Zennaro M.-C., Boulkroun S., Fernandes-Rosa F.L. Pathogenesis and treatment of primary aldosteronism. Nat Rev Endocrinol. 2020;16(10):578–89. Doi: 10.1038/s41574-020-0382-4.


16. Whelton P.K., Carey R.M., Aronow W.S., et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127–248. Doi: 10.1016/j.jacc.2017.11.006.


17. Williams B., Mancia G., Spiering W., et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021–104.


18. National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management. NICE Guideline. 2019.


19. McCormack T., Boffa R.J., Jones N.R., et al. The 2018 ESC/ESH hypertension guideline and the 2019 NICE hypertension guideline, how and why they differ. Eur Heart J. 2019;40(42):3456–58. Doi: 10.1093/eurheartj/ehz681.


20. Funder J.W., Carey R.M., Mantero F., et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–916. Doi: 10.1210/jc.2015-4061.


21. Hundemer G.L., Imsirovic H., Vaidya A., et al. Screening rates for primary aldosteronism among individuals with hypertension plus hypokalemia: a population-based retrospective cohort study. Hypertension. 2022;79(1):178–86. Doi: 10.1161/HYPERTENSIONAHA.121.18118.


22. Jaffle G., et al. Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study. Hypertension. 2020;75(3):650–59. Doi: 10.1161/HYPERTENSIONAHA.119.14359.


23. Zekarias K., Tessier K.M. Screening Rate for Primary Aldosteronism Among Patients With Treatment–Resistant Hypertension: Retrospective Analysis of Current Practice. Endocr Pract. 2022;28(3):271–75. Doi: 10.1016/j.eprac.2021.11.085.


24. Ruhle B.C., et al. Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives. Surgery. 2019;165(1):221–27. Doi: 10.1016/j.surg.2018.05.085.


25. Young W. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019;285(2):126–48. Doi: 10.1111/joim.12831.


26. Kayser S.C., Dekkers T., Groenewoud H.J., et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J Clin Endocrinol Metab. 2016;101(7):2826–35. Doi: 10.1210/jc.2016-1472.


27. Libianto R., Russell G.M., Stowasser M., et al. Detecting primary aldosteronism in Australian primary care: a prospective study. Med J Aust. 2022;216(8):408–12. Doi: 10.5694/mja2.51438.


28. O’Shea P.M., Griffin T.P., Denieffe S., Fitzgibbon M.C. The aldosterone to renin ratio in the diagnosis of primary aldosteronism: promises and challenges. Int J Clin Pract. 2019;73(7):e13353. Doi: 10.1111/ijcp.13353.


29. Yozamp N., Hundemer G.L., Moussa M., et al. Intraindividual variability of aldosterone concentrations in primary aldosteronism: implications for case detection. Hypertension. 2021;77(3):891–99. Doi: 10.1161/HYPERTENSIONAHA.120.16429.


30. Young W.F. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66(5):607–18. Doi: 10.1111/j.1365-2265.2007.02775.x.


31. Stowasser M., Gordon R.D. Primary aldosteronism: changing definitions and new concepts of physiology and pathophysiology both inside and outside the kidney. Physiol Rev. 2016;96(4):1327–84. Doi: 10.1152/physrev.00026.2015.


32. Logan A.G. Hypertension in aging patients. Exper. Rev Cardiovasc Ther. 2011;9(1):113–20. Doi: 10.1586/erc.10.171.


33. Hacini I., De Sousa K., Boulkroun S., et al. Somatic mutations in adrenals from patients with primary aldosteronism not cured after adrenalectomy suggest common pathogenic mechanisms between unilateral and bilateral disease. Eur J Endocrinol. 2021;185(3):405–12. Doi: 10.1530/EJE-21-0338.


34. Williams T.A., Lenders J.W.M., Mulatero P., et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet. Diab Endocrinol. 2017;5(9):689–99. Doi: 10.1016/S2213-8587(17)30135-3.


35. Демидова Т.Ю., Титова В.В. Сложности диагностики первичного гиперальдостеронизма. FOCUS Эндокринология. 2023;4(2):59–68.


36. Williams B., MacDonald T.M., Morant S., et al; British Hypertension Society’s PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059–68. Doi: 10.1016/S0140-6736(15)00257-3.


37. Williams B., MacDonald T.M., Morant S.V., et al; British Hypertension Society programme of Prevention And Treatment of Hypertension With Algorithm based Therapy (PATHWAY) Study Group. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. Lancet. Diab Endocrinol. 2018;6(6):464–75. Doi: 10.1016/S2213-8587(18)30071-8.


38. Parksook W.W., Yozamp N., Hundemer G.L., et al. Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism. Am J Hypertens. 2022;35(6):561–71. Doi: 10.1093/ajh/hpab189. doi: 10.1093/ajh/hpab189.


39. Dekkers T., Ter Meer M., Lenders J.W.M., et al. Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit? J Clin Endocrinol Metab. 2014;99:E1341–51. Doi: 10.1210/jc.2013-4255.


40. Boulkroun S., Samson-Couterie B., Dzib J.F., et al. Adrenal cortex remodeling and functional zona glomerulosa hyperplasia in primary aldosteronism. Hypertension. 2010;56:885–92. Doi: 10.1161/HYPERTENSIONAHA.110.158543.


41. Hahner S., Stuermer A., Kreissl M., et al.


42. Wu X, Senanayake R, Goodchild E et al.


43. Monticone S., Castellano I., Versace K., et al. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. Mol Cell Endocrinol. 2015;411:146–54. Doi: 10.1016/j.mce.2015.04.022.


44. Nakamura Y., Kitada M., Satoh F., et al. Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17. Mol Cell Endocrinol. 2016;422:57–63. Doi: 10.1016/j.mce.2015.11.014.


45. Ono Y., Yamazaki Y., Omata K., et al. Histological characterization of aldosterone-producing adrenocortical adenomas with different somatic mutations. J Clin Endocrinol Metab. 2020;105:pii dgz235. Doi: 10.1210/clinem/dgz235.


46. Gao X., Yamazaki Y., Tezuka Y., et al. The Genotype-Based Morphology of Aldosterone-Producing Adrenocortical Disorders and Their Association with Aging. Endocrinol Metab (Seoul). 2021;36(1):12–21. Doi: 10.3803/EnM.2021.101.


47. Nishimoto K., Koga M., Seki T., et al. Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. Mol Cell Endocrinol. 2017;441:12433. Doi: 10.1016/j.mce.2016.10.014.


48. Samnani S., Cenzer I., Kline G.A., et al. Time to Benefit of Surgery vs Targeted Medical Therapy for Patients With Primary Aldosteronism: A Meta-analysis. J. Clin. Endocrinol. Metab. 2024;109(3):e1280–89. Doi: 10.1210/clinem/dgad654.


49. Lu Y.C., Liu K.L., Wu V.C., et al.; TAIPAI Study Group. Unilateral adrenalectomy in bilateral adrenal hyperplasia with primary aldosteronism. J Formos Med Assoc. 2023;122(5):393–99. Doi: 10.1016/j.jfma.2022.12.015.


50. Tagawa M., Ghosn M., Wachtel H., et al. Lateralization index but not contralateral suppression at adrenal vein sampling predicts improvement in blood pressure after adrenalectomy for primary aldosteronism. J Hum Hypertens. 2017;31:444–49. Doi: 10.1038/jhh.2016.92.


51. Pitt B., Zannad F., Remme W.J., et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med. 1999;341(10):709–17. Doi: 10.1056/NEJM199909023411001.


52. Beuschlein F., Boulkroun S., Osswald A., et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet. 2013;45(4):440–44. Doi: 10.1038/ng.2550.


53. Jeunemaitre X., Chatellier G., Kreft-Jais C., et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol. 1987;60(10):820–25. Doi: 10.1016/0002-9149(87)91030-7.


54. Parthasarathy H.K., Menard J., et al. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J Hypertens. 2011;29(5):980–90. Doi: 10.1097/HJH.0b013e3283455ca5.


55. Choi M., Scholl U.I., Yue P., et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011;331(6018):768–72. Doi: 10.1126/science.1198785.


56. Williams T.A., Reincke M. Pathophysiology and histopathology of primary aldosteronism. Trends Endocrinol Metab. 2022;33(1):36–49. Doi: 10.1016/j.tem.2021.10.002.


57. Ding J., Tong A., Hacker M., et al. Usefulness of 68Ga-pentixafor PET/CT on diagnosis and management of Cushing syndrome. Clin Nucl Med. 2022;47(8):669–76. Doi: 10.1097/RLU.0000000000004244


58. Hu J., Xu T., Shen H., et al. Accuracy of gallium-68 pentixafor positron emission tomography-computed tomography for subtyping diagnosis of primary aldosteronism. JAMA. Network Open. 2023;6(2):e2255609. Doi: 10.1001/jamanetworkopen.2022.55609.


59. Chaman Baz A.H., van de Wiel E., Groenewoud H.,et al. Protocol: CXCR4-directed


60. Scholl U.I., Abriola L., Zhang C., et al. Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma. J Clin Invest. 2017;127(7):2739–50. Doi: 10.1172/JCI91733.


61. Freeman M.W., Halvorsen Y.D., Marshall W., et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med. 2023;388(5):395–405. Doi: 10.1056/NEJMoa2213169.


Об авторах / Для корреспонденции


Автор для связи: Дарья Олеговна Ладыгина, к.м.н., доцент кафедры эндокринологии № 1 Института клинической медицины им. Н.В. Скли-фосовского, Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет), Москва, Россия; d8050005@gmail.com 


ORCID / eLibrary SPIN: 
Д.О. Ладыгина (D.O. Ladygina), ORCID: https://orcid.org/0000-0001-6418-7060; eLibrary SPIN: 7958-9435
А.А. Вастистова (A.A. Vastistova), ORCID: https://orcid.org/0009-0005-9587-8370 
Е.С. Шиленкова (E.S. Shilenkova), ORCID: https://orcid.org/0009-0004-5109-5027 
Н.М. Платонова (N.M. Platonova), ORCID: https://orcid.org/0000-0001-6388-1544; eLibrary SPIN: 4053-3033 
Д.Г. Бельцевич (D.G. Beltsevich), ORCID: https://orcid.org/0000-0001-7098-4584; eLibrary SPIN: 4475-6327
В.В. Фадеев (V.V. Fadeev), ORCID: https://orcid.org/0000-0002-3026-6315; eLibrary SPIN: 6825-8417


Похожие статьи


Бионика Медиа