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PRIMARY ALDOSTERONISM: CURRENT DIAGNOSTIC APPROACH

https://doi.org/10.57256/2949-0715-2022-1-11-23

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Abstract

Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the hypertension, hypokalemia, and it also increases the risk for cardiovascular and kidney disease, as well as death. Current evidence suggests that the prevalence of primary aldosteronism is much greater than previously recognized and milder forms of renin-independent aldosterone secretion may be common. These forms may be missed. This review focused screening in those at increased risk of primary aldosteronism. An approach to evaluating screening results was presented. Family aldosteronism should be considered in young hypertensive patients with a family history of primary aldosteronism. Genetic testing is appropriate in these patients. Careful interpretation of screening data, recent achievements in hormone assays and sampling methods and their clinical relevance are discussed. Confirmatory tests and evaluation of their results are considered. The optimal approach to distinguish unilateral from bilateral primary aldosteronism is by adrenal vein sampling that is the only reliable method to select patients for surgery. More effective strategy to diagnose PA should lead to early detection of PA and could decrease the cardiovascular complications of the patients.

For citations:


Eniseeva E. PRIMARY ALDOSTERONISM: CURRENT DIAGNOSTIC APPROACH. Baikal Medical Journal. 2022;1(1):11-23. (In Russ.) https://doi.org/10.57256/2949-0715-2022-1-11-23

Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the hypertension, hypokalemia, and it also increases the risk for cardiovascular and kidney disease, as well as death. Current evidence suggests that the prevalence of primary aldosteronism is much greater than previously recognized and milder forms of renin-independent aldosterone secretion may be common. These forms may be missed. This review focused screening in those at increased risk of primary aldosteronism. An approach to evaluating screening results was presented. Family aldosteronism should be considered in young hypertensive patients with a family history of primary aldosteronism. Genetic testing is appropriate in these patients. Careful interpretation of screening data, recent achievements in hormone assays and sampling methods and their clinical relevance are discussed. Confirmatory tests and evaluation of their results are considered. The optimal approach to distinguish unilateral from bilateral primary aldosteronism is by adrenal vein sampling that is the only reliable method to select patients for surgery. More effective strategy to diagnose PA should lead to early detection of PA and could decrease the cardiovascular complications of the patients

References

1. 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):1889-1916. https://doi.org/10.1210/jc.2015-4061

2. 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):1811-1820. https://doi.org/10.1016/j.jacc.2017.01.052

3. Mulatero P., Monticone S., Deinum J. et al. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens. 2020;38(10):1919-1928. https://doi.org/10.1097/HJH.0000000000002510

4. Vaidya A., Carey R.M. Evolution of the Primary Aldosteronism Syndrome: Updating the Approach [published correction appears in J Clin Endocrinol Metab. 2021 Jan 1;106(1):e414]. J Clin Endocrinol Metab. 2020;105(12):3771-3783. https://doi.org/10.1210/clinem/dgaa606

5. Mulatero P, Monticone S, Burrello J, et al. Guidelines for primary aldosteronism: uptake by primary care physicians in Europe. J Hypertens. 2016;34(11):2253-2257. https://doi.org/10.1097/hjh.0000000000001088

6. Buffolo F., Monticone S., Burrello J. et al. Is Primary Aldosteronism Still Largely Unrecognized? Horm Metab Res. 2017;49(12):908-914. https://doi.org/10.1055/s-0043-119755

7. Brown J.M., Siddiqui M., Calhoun D.A. et al. The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study. Ann Intern Med. 2020;173(1):10-20. https://doi.org/10.7326/m20-0065

8. 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 Diabetes Endocrinol. 2018;6(1):41-50. https://doi.org/10.1016/s2213-8587(17)30319-4

9. Young W.F. Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019;285:126-148. https://doi.org/10.1111/joim.12831

10. Turcu A.F., Nhan W., Grigoryan S. et al. Primary Aldosteronism Screening Rates Differ with Sex, Race, and Comorbidities. J Am Heart Assoc. 2022;11(14):e025952. https://doi.org/10.1161/jaha.122.025952

11. Hundemer G.L., Curhan G.C., Yozamp N., Wang M., Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018;6(1):51-59. https://doi.org/10.1016/s2213-8587(17)30367-4

12. Chen Z.W., Huang K.C., Lee J.K. et al. Aldosterone induces left ventricular subclinical systolic dysfunction: a strain imaging study. J Hypertens. 2018;36(2):353-360. https://doi.org/10.1097/hjh.0000000000001534

13. Parasiliti-Caprino M., Lopez C., Prencipe N. et al. Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension. J Hypertens. 2020;38(9):1841-1848. https://doi.org/10.1097/hjh.0000000000002441

14. Fernández-Argüeso M., Pascual-Corrales E., Bengoa Rojano N. et al. Higher risk of chronic kidney disease and progressive kidney function impairment in primary aldosteronism than in essential hypertension. Case-control study. Endocrine. 2021;73(2):439-446. https://doi.org/10.1007/s12020-021-02704-2

15. Lin X., Ullah M.H.E., Wu X. et al. Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism. Front. Cardiovasc. Med. 2022;8:798364. https://doi.org/10.3389/fcvm.2021.798364

16. Bioletto F., Bollati M., Lopez C. et al. Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight. Int J Mol Sci. 2022;23:4803. https://doi.org/10.3390/ijms23094803

17. Tyfoxylou E., Voulgaris N., Gravvanis C. et al. High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension. Biomedicines. 2022;10(9):2308. https://doi.org/10.3390/biomedicines10092308

18. Moustaki M., Paschou S.A., Vakali E.C., Vryonidou A. Secondary diabetes mellitus due to primary aldosteronism. Endocrine. 2022;10.1007/s12020-022-03168-8. https://doi.org/10.1007/s12020-022-03168-8

19. Wu V.C., Chueh S.J., Chen L. et al. Risk of new-onset diabetes mellitus in primary aldosteronism: a population study over 5 years. J Hypertens. 2017;35(8):1698-1708. https://doi.org/10.1097/hjh.0000000000001361

20. Zennaro M.C., Jeunemaitre X.. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism. Ann Endocrinol (Paris). 2016;77(3):214-219. https://doi.org/10.1016/j.ando.2016.02.006

21. de Freminville J.B., Amar L. How to Explore an Endocrine Cause of Hypertension. J Clin Med. 2022;11(2):420. https://doi.org/10.3390/jcm11020420

22. Scholl U.I. Genetics of Primary Aldosteronism. Hypertension. 2022;79(5):887-897. https://doi.org/10.1161/hypertensionaha.121.16498

23. Monticone S., Buffolo F., Tetti M. et al. GENETICS IN ENDOCRINOLOGY: the expanding genetic horizon of primary aldosteronism. Eur J Endocrinol. 2018;178:R101–R111. https://doi.org/ 10.1530/eje-17-0946

24. Prada E.T.A., Burrello J., Reincke M., Williams T.A. Old and new concepts in the molecular pathogenesis of primary aldosteronism. Hypertension. 2017;70:875-881. https://doi.org/10.1161/hypertensionaha.117.10111

25. Rossi G.P., Bisogni V., Bacca A.V. et al. The 2020 Italian Society of Arterial Hypertension (SIIA) Practical Guidelines for the Management of Primary Aldosteronism. Int. J. Cardiol. Hypertens. 2020;5:100029. https://doi.org/10.1016/j.ijchy.2020.100029

26. Scholl U.I., Stolting G., Schewe J. et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet. 2018;50:349-354. https://doi.org/10.1038/s41588-018-0048-5

27. Fernandes-Rosa F.L., Daniil G., Orozco I.J. et al. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet. 2018;50:355-361. https://doi.org/10.1038/s41588-018-0053-8

28. Monticone S., Tetti M., Burrello J. et al. Familial hyperaldosteronism type III. J Hum Hypertens. 2017;31:776-781. https://doi.org/10.1038/jhh.2017.34

29. Reimer E.N., Walenda G., Seidel E., Scholl U.I. CACNA1H(M1549 V) mutant calcium channel causes autonomous aldosterone production in HAC15 cells and is inhibited by mibefradil. Endocrinology. 2016;157:3016-3022. https://doi.org/10.1210/en.2016-1170

30. Daniil G., Fernandes-Rosa F.L., Chemin J. et al. CACNA1H mutations are associated with different forms of primary aldosteronism. EBioMedicine 2016;13:225–236. https://doi.org/10.1016/j.ebiom.2016.10.002

31. Brown J.M., Robinson-Cohen C., Luque-Fernandez M.A. et al. The spectrum of subclinical primary aldosteronism and incident hypertension: a cohort study. Ann Intern Med. 2017;167:630-641. https://doi.org/10.7326/m17-0882

32. Monticone S., Losano I., Tetti M. et al. Diagnostic approach to low-renin hypertension. Clin Endocrinol (Oxf). 2018;89:385-396. https://doi.org/10.1111/cen.13741

33. 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 Diabetes Endocrinol. 2017;5(9):689-699. https://doi.org/10.1016/s2213-8587(17)30135-3

34. Käyser S.C., Deinum J., de Grauw W.J.C. et al. Prevalence of primary aldosteronism in primary care: a cross-sectional study. Br J Gen Pract. 2018;68(667):e114-e122. https://doi.org/10.3399/bjgp18x694589

35. Widimský J., Bruthans J., Wohlfahrt P. et al. Primary aldosteronism in a general population sample. The Czech post-MONICA study. Blood Press. 2020;29(3):191-198. https://doi.org/10.1080/08037051.2020.1723406

36. Rossi E., Perazzoli F., Negro A., Magnani A. Diagnostic rate of primary aldosteronism in Emilia-Romagna, Northern Italy, during 16 years (2000-2015). J Hypertens. 2017;35:1691-1697. https://doi.org/10.1097/hjh.0000000000001384

37. Baudrand R., Guarda F.J., Fardella C. et al. Continuum of renin-independent aldosteronism in normotension. Hypertension. 2017;69(5):950-956. https://doi.org/10.1161/hypertensionaha.116.08952

38. Karashima S., Kometani M., Tsujiguchi H. et al. Prevalence of primary aldosteronism without hypertension in the general population: Results in Shika study. Clin Exp Hypertens. 2018;40(2):118-125. https://doi.org/10.1080/10641963.2017.1339072

39. Vaidya A., Mulatero P., Baudrand R., Adler G.K. The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment. Endocr Rev. 2018; 39:1057-1088. https://doi.org/10.1210/er.2018-00139

40. Dekkers T., Prejbisz A., Kool L.J.S. et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016;4(9):739-746. https://doi.org/10.1016/s2213-8587(16)30100-0

41. Alam S., Kandasamy D., Goyal A. et al. High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension. Clin Endocrinol (Oxf). 2021;94(6):895-903. https://doi.org/10.1111/cen.14409

42. Burrello J., Monticone S., Losano I. et al. Prevalence of hypokalemia and primary aldosteronism in 5100 patients referred to a tertiary hypertension unit. Hypertension. 2020;75:1025-1033. https://doi.org/10.1161/hypertensionaha.119.14063

43. Li L., Yang G., Zhao L. et al. Baseline demographic and clinical characteristics of patients with adrenal incidentaloma from a single center in China: a survey. Int J Endocrinol. 2017;3093290. https://doi.org/10.1155/2017/3093290

44. Fassnacht M., Arlt W., Bancos I. et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016;175(2):G1-G34. https://doi.org/10.1530/eje-16-0467

45. Stavropoulos K., Imprialos K.P., Katsiki N. et al. Primary aldosteronism in patients with adrenal incidentaloma: Is screening appropriate for everyone?.J Clin Hypertens (Greenwich). 2018;20(5):942-948. https://doi.org/10.1111/jch.13291

46. Bancos I., Prete A. Approach to the patient with adrenal incidentaloma. J Clin Endocrinol Metab. 2021;106(11):3331-3353. https://doi.org/10.1210/clinem/dgab512

47. Seccia T.M., Letizia C., Muiesan M.L. et al. Atrial fibrillation as presenting sign of primary aldosteronism: results of the PAPPHY Study. J Hypertens. 2020;38:332-339. https://doi.org/10.1097/hjh.0000000000002250

48. Rossi G.P., Maiolino G., Flego A. et al. PAPY Study Investigators. Adrenalectomy lowers incident atrial fibrillation in primary aldosteronism patients at long term. Hypertension. 2018;71:585-591. https://doi.org/10.1161/hypertensionaha.117.10596

49. Gao H., Luo R., Li J., Tian H. Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: a systematic review and meta-analysis. Ann Transl Med. 2022;10(12):679. https://doi.org/10.21037/atm-22-2272

50. Baron S., Amar L., Faucon A.L. et al. Criteria for diagnosing primary aldosteronism on the basis of liquid chromatography-tandem mass spectrometry determinations of plasma aldosterone concentration. J Hypertens. 2018;36:1592-1601. https://doi.org/10.1097/hjh.0000000000001735

51. Guo Z., Poglitsch M., McWhinney B.C. et al. Aldosterone LC-MS/MS assay-specific threshold values in screening and confirmatory testing for primary aldosteronism. J Clin Endocrinol Metab. 2018;103:3965-3973. https://doi.org/10.1210/jc.2018-01041

52. Maiolino G., Rossitto G., Bisogni V. et al. Quantitative value of aldosterone-renin ratio for detection of aldosterone- producing adenoma: the aldosterone-renin ratio for primary aldosteronism (AQUARR) study. J Am Heart Assoc. 2017;6:e005574. https://doi.org/10.1161/jaha.117.005574

53. Veldhuizen G.P., Alnazer R.M., Kroon A.A., de Leeuw P.W. Confounders of the aldosterone-to-renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature. J Clin Hypertens (Greenwich). 2021;23(2):201-207. https://doi.org/10.1111/jch.14117

54. Burrello J., Monticone S., Buffolo F. et al. Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in primary aldosteronism. J Hypertens. 2016;34:920-927. https://doi.org/10.1097/hjh.0000000000000880

55. Manolopoulou J., Fischer E., Dietz A. et al. Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. J Hypertens. 2015;33:2500-2511. https://doi.org/10.1097/hjh.0000000000000727

56. Rossi G.P., Ceolotto G., Rossitto G. et al. Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension. Clin Chem Lab Med. 2016;54:1441-1450. https://doi.org/10.1515/cclm-2015-1094

57. Teruyama K., Naruse M., Tsuiki M., Kobayashi H. Novel chemiluminescent immunoassay to measure plasma aldosterone and plasma active renin concentrations for the diagnosis of primary aldosteronism. J Hum Hypertens. 2022;36(1):77-85. https://doi.org/10.1038/s41371-020-00465-5

58. 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):891-899. https://doi.org/10.1161/hypertensionaha.120.16429

59. Mirfakhraee S., Rodriguez M., Ganji N. et al. A real saline challenge: diagnosing primary aldosteronism in the setting of chronic kidney disease. J Investig Med High Impact Case Rep. 2021;9:23247096211034337. https://doi.org/10.1177/23247096211034337

60. Alnazer R.M., Veldhuizen G.P., Kroon A.A., de Leeuw P.W. The effect of medication on the aldosterone-to-renin ratio. A critical review of the literature. J Clin Hypertens (Greenwich). 2021;23(2):208-214. https://doi.org/:10.1111/jch.14173

61. Jędrusik P., Symonides B., Lewandowski J., Gaciong Z. The effect of antihypertensive medications on testing for primary aldosteronism. Front Pharmacol. 2021;12:684111. https://doi.org/10.3389/fphar.2021.684111

62. Ahmed A.H., Gordon R.D., Ward G. et al. Effect of moxonidine on the aldosterone/renin ratio in healthy male volunteers. J Clin Endocrinol Metab. 2017;102:2039-2043. https://doi.org/10.1210/jc.2016-3821

63. Baudrand R., Guarda F.J., Torrey J., Williams G., Vaidya A. Dietary sodium restriction increases the risk of misinterpreting mild cases of primary aldosteronism. J Clin Endocrinol Metab. 2016;101:3989-3996. https://doi.org/10.1210/jc.2016-1963

64. Amar L., Baguet J.P., Bardet S. et al. SFE/SFHTA/AFCE Primary aldosteronism consensus: introduction and handbook. Ann Endocrinol (Paris). 2016;77:179-186. https://doi.org/10.1016/j.ando.2016.05.001

65. Reznik Y., Amar L., Tabarin A. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 3: Confirmatory testing. Annal Endocrinol (Paris). 2016;77:202-207. https://doi.org/10.1016/j.ando.2016.01.007

66. Endokrinologiya: natsional'noe rukovodstvo. Pod red. Dedova I.I., Mel'nichenko G.A. 2-e izd., pererab. i dop. M.: GEOTAR-Media; 2022:845 (In Russian)

67. Leung A.A., Symonds C.J., Hundemer G.L. et al. Performance of confirmatory tests for diagnosing primary aldosteronism: a systematic review and meta-analysis. Hypertension. 2022;79:1835–1844. https://doi.org/10.1161/hypertensionaha.122.19377

68. Mulatero P., Sechi L.A., Williams T.A. et al. Subtype diagnosis, treatment, complications and outcomes of primary aldosteronism and future direction of research: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020;38:1929-1936. https://doi.org/10.1097/hjh.0000000000002520

69. Omura K., Ota H., Takahashi Y. et al. Anatomical variations of the right adrenal vein: concordance between multidetector computed tomography and catheter venography. Hypertension. 2017;69:428-434. https://doi.org/10.1161/hypertensionaha.116.08375

70. Tezuka Y., Yamazaki Y., Nakamura Y. et al. Recent development toward the next clinical practice of primary aldosteronism: a literature review. Biomedicines. 2021;9(3):310. https://doi.org/10.3390/biomedicines9030310

71. Williams T.A., Burrello J., Sechi L.A. et al. Computed tomography and adrenal venous sampling in the diagnosis of unilateral primary aldosteronism. Hypertension. 2018;72:641-649. https://doi.org/10.1161/hypertensionaha.118.11382

72. Umakoshi H., Ogasawara T., Takeda Y. et al. Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism. Clin Endocrinol (Oxf). 2018;88:645-651. https://doi.org/10.1111/cen.13582

73. Wolley M.J., Stowasser M. New advances in the diagnostic work-up of primary aldosteronism. J Endocr Soc. 2017;1:149-161. https://doi.org/10.1210/js.2016-1107

74. Wolley M., Thuzar M., Stowasser M. Controversies and advances in adrenal venous sampling in the diagnostic workup of primary aldosteronism. Best Pract Res Clin Endocrinol Metab. 2020;34(3):101400. https://doi.org/10.1016/j.beem.2020.101400

75. Loberg C., Antoch G., Stegbauer J. et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Rofo. 2021;193(6):658-666. https://doi.org/10.1055/a-1299-1878

76. Ladurner R., Sommerey S., Buechner S. et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest. 2017;47(5):372-377. https://doi.org/10.1111/eci.12746

77. Dekkers T., Prejbisz A., Kool L.J.S. et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016;4(9):739-746. https://doi.org/10.1016/s2213-8587(16)30100-0

78. Beuschlein F., Mulatero P., Asbach E. et al. The SPARTACUS Trial: controversies and unresolved issues. Horm Metab Res. 2017;49:936–942. https://doi.org/10.1055/s-0043-120524

79. Ohno Y., Naruse M., Beuschlein F. et al. Adrenal venous sampling-guided adrenalectomy rates in primary aldosteronism: results of an international cohort (AVSTAT). J Clin Endocrinol Metab. 2021;106(3):e1400-e1407. https://doi.org/10.1210/clinem/dgaa706


About the Author

Elena S. Eniseeva
Irkutsk State Medical Academy of Postgraduate Education – Branch of Russian Medical Academy of Continuing Professional Education, Irkutsk State Medical University
Russian Federation

Cand.Med.Sci., associated professor, 


Competing Interests:

Автор заявляет об отсутствии явных и потенциальных конфликтов интересов, связанных с публикацией настоящей
статьи.



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For citations:


Eniseeva E. PRIMARY ALDOSTERONISM: CURRENT DIAGNOSTIC APPROACH. Baikal Medical Journal. 2022;1(1):11-23. (In Russ.) https://doi.org/10.57256/2949-0715-2022-1-11-23

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ISSN 2949-0715 (Online)

Irkutsk State Medical University

Irkutsk Scientific Center for Surgery and Traumatology