Endocrinol Metab.  2023 Dec;38(6):597-618. 10.3803/EnM.2023.1789.

2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism

• Ha J
• Park JH
• Kim KJ
• Kim JH
• Jung KY
• Lee J
• Choi JH
• Lee SH
• Hong N
• Lim JS
• Park BK
• Kim JH
• Jung KC
• Cho J
• Kim Mk
• Chung CH
• The Committee of Clinical Practice Guideline of Korean Endocrine Society
• The Korean Adrenal Study Group of Korean Endocrine Society

• KMID: 2549255
• DOI: http://doi.org/10.3803/EnM.2023.1789

Abstract

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

Keyword

Primary aldosteronism; Hypertension; Diagnosis; Treatment; Guideline

Figure

• 

  Fig. 1. Suggested diagnostic process for patients with primary aldosteronism. BP, blood pressure; ARR, aldosterone-to-renin ratio; PAC, plasma aldosterone concentration; PRA, plasma renin activity; DRC, direct renin concentration; CT, computed tomography; MRA, mineralocorticoid receptor antagonist. aConsider using PAC >15 ng/dL as a screening cutoff if the renin level is excessively suppressed.

Reference

1. Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017; 69:1811–20.

2. El Ghorayeb N, Bourdeau I, Lacroix A. Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism. Front Endocrinol (Lausanne). 2016; 7:72.

3. Bhalla V, Hallows KR. Mechanisms of ENaC regulation and clinical implications. J Am Soc Nephrol. 2008; 19:1845–54.

4. Conn JW. Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med. 1955; 45:3–17.

5. Stowasser M, Gordon RD. Primary aldosteronism: changing definitions and new concepts of physiology and pathophysiology both inside and outside the kidney. Physiol Rev. 2016; 96:1327–84.

6. Murata M, Kitamura T, Tamada D, Mukai K, Kurebayashi S, Yamamoto T, et al. Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism. J Hypertens. 2017; 35:1079–85.

7. Salcuni AS, Carnevale V, Battista C, Palmieri S, Eller-Vainicher C, Guarnieri V, et al. Primary aldosteronism as a cause of secondary osteoporosis. Eur J Endocrinol. 2017; 177:431–7.

8. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Renal outcomes in medically and surgically treated primary aldosteronism. Hypertension. 2018; 72:658–66.

9. Mulatero P, Monticone S, Bertello C, Viola A, Tizzani D, Iannaccone A, et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab. 2013; 98:4826–33.

10. Lee JY, Kim DA, Choi E, Lee YS, Park SJ, Kim BJ. Aldosterone inhibits in vitro myogenesis by increasing intracellular oxidative stress via mineralocorticoid receptor. Endocrinol Metab (Seoul). 2021; 36:865–74.

11. Moon SJ, Jang HN, Kim JH, Moon MK. Lipid profiles in primary aldosteronism compared with essential hypertension: propensity-score matching study. Endocrinol Metab (Seoul). 2021; 36:885–94.

12. Lim JS, Park S, Park SI, Oh YT, Choi E, Kim JY, et al. Cardiac dysfunction in association with increased inflammatory markers in primary aldosteronism. Endocrinol Metab (Seoul). 2016; 31:567–76.

13. Olivieri O, Ciacciarelli A, Signorelli D, Pizzolo F, Guarini P, Pavan C, et al. Aldosterone to renin ratio in a primary care setting: the Bussolengo study. J Clin Endocrinol Metab. 2004; 89:4221–6.

14. Kaplan NM. Hypokalemia in the hypertensive patient, with observations on the incidence of primary aldosteronism. Ann Intern Med. 1967; 66:1079–90.

15. Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004; 89:1045–50.

16. Xu Z, Yang J, Hu J, Song Y, He W, Luo T, et al. Primary aldosteronism in patients in china with recently detected hypertension. J Am Coll Cardiol. 2020; 75:1913–22.

17. Libianto R, Russell GM, Stowasser M, Gwini SM, Nuttall P, Shen J, et al. Detecting primary aldosteronism in Australian primary care: a prospective study. Med J Aust. 2022; 216:408–12.

18. Kayser SC, Dekkers T, Groenewoud HJ, van der Wilt GJ, Carel Bakx J, van der Wel MC, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J Clin Endocrinol Metab. 2016; 101:2826–35.

19. Gao X, Yamazaki Y, Tezuka Y, Omata K, Ono Y, Morimoto R, et al. The genotype-based morphology of aldosterone-producing adrenocortical disorders and their association with aging. Endocrinol Metab (Seoul). 2021; 36:12–21.

20. Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, et al. The spectrum of subclinical primary aldosteronism and incident hypertension: a cohort study. Ann Intern Med. 2017; 167:630–41.

21. Yoon M, Hong N, Ha J, Lee CJ, Ku CR, Rhee Y, et al. Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. Hypertens Res. 2022; 45:1418–29.

22. Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann Intern Med. 2020; 173:10–20.

23. Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023; 189:G1–42.

24. Buffolo F, Li Q, Monticone S, Heinrich DA, Mattei A, Pieroni J, et al. Primary aldosteronism and obstructive sleep apnea: a cross-sectional multi-ethnic study. Hypertension. 2019; 74:1532–40.

25. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101:1889–916.

26. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, 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. Hypertension. 2018; 71:e13–115.

27. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC task force for the management of arterial hypertension. J Hypertens. 2018; 36:2284–309.

28. Naruse M, Katabami T, Shibata H, Sone M, Takahashi K, Tanabe A, et al. Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021. Endocr J. 2022; 69:327–59.

29. Alam S, Kandasamy D, Goyal A, Vishnubhatla S, Singh S, Karthikeyan G, et al. High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension. Clin Endocrinol (Oxf). 2021; 94:895–903.

30. Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, 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; 38:1919–28.

31. Choi M, Scholl UI, Yue P, Bjorklund P, Zhao B, Nelson-Williams C, et al. K+ channel mutations in adrenal aldosteroneproducing adenomas and hereditary hypertension. Science. 2011; 331:768–72.

32. Scholl UI, Goh G, Stolting G, de Oliveira RC, Choi M, Overton JD, et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet. 2013; 45:1050–4.

33. Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen HN, Lichtenauer UD, et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet. 2013; 45:440–4.

34. Scholl UI, Stolting G, Nelson-Williams C, Vichot AA, Choi M, Loring E, et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife. 2015; 4:e06315.

35. Teo AE, Garg S, Shaikh LH, Zhou J, Karet Frankl FE, Gurnell M, et al. Pregnancy, primary aldosteronism, and adrenal CTNNB1 mutations. N Engl J Med. 2015; 373:1429–36.

36. Murtha TD, Carling T, Scholl UI. Pregnancy, primary aldosteronism, and somatic CTNNB1 mutations. N Engl J Med. 2016; 374:1492–3.

37. Zhou J, Azizan EA, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, et al. Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nat Genet. 2021; 53:1360–72.

38. Nanba K, Rainey WE. Genetics in endocrinology: impact of race and sex on genetic causes of aldosterone-producing adenomas. Eur J Endocrinol. 2021; 185:R1–11.

39. Hong AR, Kim JH, Song YS, Lee KE, Seo SH, Seong MW, et al. Genetics of aldosterone-producing adenoma in Korean patients. PLoS One. 2016; 11:e0147590.

40. Mulatero P, Tizzani D, Viola A, Bertello C, Monticone S, Mengozzi G, et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension. 2011; 58:797–803.

41. Miyahara K, Kawamoto T, Mitsuuchi Y, Toda K, Imura H, Gordon RD, et al. The chimeric gene linked to glucocorticoid-suppressible hyperaldosteronism encodes a fused P-450 protein possessing aldosterone synthase activity. Biochem Biophys Res Commun. 1992; 189:885–91.

42. Monticone S, Buffolo F, Tetti M, Veglio F, Pasini B, Mulatero P. Genetics in endocrinology: the expanding genetic horizon of primary aldosteronism. Eur J Endocrinol. 2018; 178:R101–11.

43. Scholl UI, Stolting G, Schewe J, Thiel A, Tan H, Nelson-Williams C, et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet. 2018; 50:349–54.

44. Fernandes-Rosa FL, Daniil G, Orozco IJ, Goppner C, El Zein R, Jain V, et al. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet. 2018; 50:355–61.

45. Morganti A; European study group for the validation of DiaSorin LIAISON Direct Renin Assay. A comparative study on inter and intralaboratory reproducibility of renin measurement with a conventional enzymatic method and a new chemiluminescent assay of immunoreactive renin. J Hypertens. 2010; 28:1307–12.

46. Rossi GP, Ceolotto G, Rossitto G, Seccia TM, Maiolino G, Berton C, 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; 54:1441–50.

47. Sealey JE, Laragh JH. Radioimmunoassay of plasma renin activity. Semin Nucl Med. 1975; 5:189–202.

48. Rossi GP, Bisogni V, Bacca AV, Belfiore A, Cesari M, Concistre A, 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.

49. Baron S, Amar L, Faucon AL, Blanchard A, Baffalie L, Faucard C, et al. Criteria for diagnosing primary aldosteronism on the basis of liquid chromatography-tandem mass spectrometry determinations of plasma aldosterone concentration. J Hypertens. 2018; 36:1592–601.

50. Guo Z, Poglitsch M, McWhinney BC, Ungerer JP, Ahmed AH, Gordon RD, et al. Aldosterone LC-MS/MS assay-specific threshold values in screening and confirmatory testing for primary aldosteronism. J Clin Endocrinol Metab. 2018; 103:3965–73.

51. Taylor PJ, Cooper DP, Gordon RD, Stowasser M. Measurement of aldosterone in human plasma by semiautomated HPLC-tandem mass spectrometry. Clin Chem. 2009; 55:1155–62.

52. Hiramatsu K, Yamada T, Yukimura Y, Komiya I, Ichikawa K, Ishihara M, et al. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity: results in hypertensive patients. Arch Intern Med. 1981; 141:1589–93.

53. McKenna TJ, Sequeira SJ, Heffernan A, Chambers J, Cunningham S. Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism. J Clin Endocrinol Metab. 1991; 73:952–7.

54. Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ‘nonselective’ screening of hypertensive patients. J Hypertens. 2003; 21:2149–57.

55. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007; 66:607–18.

56. Mulatero P, Monticone S, Bertello C, Tizzani D, Iannaccone A, Crudo V, et al. Evaluation of primary aldosteronism. Curr Opin Endocrinol Diabetes Obes. 2010; 17:188–93.

57. Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019; 285:126–48.

58. Stowasser M, Gordon RD. Primary aldosteronism: careful investigation is essential and rewarding. Mol Cell Endocrinol. 2004; 217:33–9.

59. Mosso L, Carvajal C, Gonzalez A, Barraza A, Avila F, Montero J, et al. Primary aldosteronism and hypertensive disease. Hypertension. 2003; 42:161–5.

60. Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, et al. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002; 40:897–902.

61. Gordon RD, Wolfe LK, Island DP, Liddle GW. A diurnal rhythm in plasma renin activity in man. J Clin Invest. 1966; 45:1587–92.

62. Rossi GP, Ceolotto G, Rossitto G, Maiolino G, Cesari M, Seccia TM. Effects of mineralocorticoid and AT1 receptor antagonism on the aldosterone-renin ratio in primary aldosteronism: the EMIRA Study. J Clin Endocrinol Metab. 2020; 105:dgaa080.

63. Murase K, Nagaishi R, Takenoshita H, Nomiyama T, Akehi Y, Yanase T. Prevalence and clinical characteristics of primary aldosteronism in Japanese patients with type 2 diabetes mellitus and hypertension. Endocr J. 2013; 60:967–76.

64. Nanba AT, Wannachalee T, Shields JJ, Byrd JB, Rainey WE, Auchus RJ, et al. Adrenal vein sampling lateralization despite mineralocorticoid receptor antagonists exposure in primary aldosteronism. J Clin Endocrinol Metab. 2019; 104:487–92.

65. Haase M, Riester A, Kropil P, Hahner S, Degenhart C, Willenberg HS, et al. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab. 2014; 99:4397–402.

66. Maiolino G, Rossitto G, Bisogni V, Cesari M, Seccia TM, Plebani M, 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.

67. Turcu AF, Yang J, Vaidya A. Primary aldosteronism: a multidimensional syndrome. Nat Rev Endocrinol. 2022; 18:665–82.

68. Mulatero P, Bertello C, Rossato D, Mengozzi G, Milan A, Garrone C, et al. Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab. 2008; 93:1366–71.

69. Patel SM, Lingam RK, Beaconsfield TI, Tran TL, Brown B. Role of radiology in the management of primary aldosteronism. Radiographics. 2007; 27:1145–57.

70. Yamazaki Y, Nakamura Y, Omata K, Ise K, Tezuka Y, Ono Y, et al. Histopathological classification of cross-sectional image-negative hyperaldosteronism. J Clin Endocrinol Metab. 2017; 102:1182–92.

71. Ebbehoj A, Li D, Kaur RJ, Zhang C, Singh S, Li T, et al. Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study. Lancet Diabetes Endocrinol. 2020; 8:894–902.

72. Reincke M, Bancos I, Mulatero P, Scholl UI, Stowasser M, Williams TA. Diagnosis and treatment of primary aldosteronism. Lancet Diabetes Endocrinol. 2021; 9:876–92.

73. Buffolo F, Monticone S, Williams TA, Rossato D, Burrello J, Tetti M, et al. Subtype diagnosis of primary aldosteronism: is adrenal vein sampling always necessary? Int J Mol Sci. 2017; 18:848.

74. Young WF, Stanson AW, Thompson GB, Grant CS, Farley DR, van Heerden JA. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004; 136:1227–35.

75. Nwariaku FE, Miller BS, Auchus R, Holt S, Watumull L, Dolmatch B, et al. Primary hyperaldosteronism: effect of adrenal vein sampling on surgical outcome. Arch Surg. 2006; 141:497–503.

76. Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, et al. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009; 151:329–37.

77. Ladurner R, Sommerey S, Buechner S, Dietz A, Degenhart C, Hallfeldt K, et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest. 2017; 47:372–7.

78. Lee SH, Kim JW, Yoon HK, Koh JM, Shin CS, Kim SW, et al. Diagnostic accuracy of computed tomography in predicting primary aldosteronism subtype according to age. Endocrinol Metab (Seoul). 2021; 36:401–12.

79. Naruse M, Tanabe A, Yamamoto K, Rakugi H, Kometani M, Yoneda T, et al. Adrenal venous sampling for subtype diagnosis of primary hyperaldosteronism. Endocrinol Metab (Seoul). 2021; 36:965–73.

80. Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014; 63:151–60.

81. Williams TA, Reincke M. Management of endocrine disease: diagnosis and management of primary aldosteronism: the Endocrine Society guideline 2016 revisited. Eur J Endocrinol. 2018; 179:R19–29.

82. Monticone S, Viola A, Rossato D, Veglio F, Reincke M, Gomez-Sanchez C, et al. Adrenal vein sampling in primary aldosteronism: towards a standardised protocol. Lancet Diabetes Endocrinol. 2015; 3:296–303.

83. Daunt N. Adrenal vein sampling: how to make it quick, easy, and successful. Radiographics. 2005; 25 Suppl 1:S143–58.

84. Park JJ, Park BK, Kim CK. Direct and indirect imaging features of adrenohepatic fusion. Abdom Radiol (NY). 2016; 41:377–83.

85. Rossi GP, Barisa M, Allolio B, Auchus RJ, Amar L, Cohen D, et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab. 2012; 97:1606–14.

86. Seccia TM, Miotto D, Battistel M, Motta R, Barisa M, Maniero C, et al. A stress reaction affects assessment of selectivity of adrenal venous sampling and of lateralization of aldosterone excess in primary aldosteronism. Eur J Endocrinol. 2012; 166:869–75.

87. Almarzooqi MK, Chagnon M, Soulez G, Giroux MF, Gilbert P, Oliva VL, et al. Adrenal vein sampling in primary aldosteronism: concordance of simultaneous vs sequential sampling. Eur J Endocrinol. 2017; 176:159–67.

88. Mulatero P, Sechi LA, Williams TA, Lenders JW, Reincke M, Satoh F, 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; 38:1929–36.

89. Satoh F, Morimoto R, Seiji K, Satani N, Ota H, Iwakura Y, et al. Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism? Eur J Endocrinol. 2015; 173:465–77.

90. Satani N, Ota H, Seiji K, Morimoto R, Kudo M, Iwakura Y, et al. Intra-adrenal aldosterone secretion: segmental adrenal venous sampling for localization. Radiology. 2016; 278:265–74.

91. Lethielleux G, Amar L, Raynaud A, Plouin PF, Steichen O. Influence of diagnostic criteria on the interpretation of adrenal vein sampling. Hypertension. 2015; 65:849–54.

92. Vaidya A, Mulatero P, Baudrand R, Adler GK. The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment. Endocr Rev. 2018; 39:1057–88.

93. Wolley MJ, Gordon RD, Ahmed AH, Stowasser M. Does contralateral suppression at adrenal venous sampling predict outcome following unilateral adrenalectomy for primary aldosteronism?: a retrospective study. J Clin Endocrinol Metab. 2015; 100:1477–84.

94. Lee SH, Kim JW, Yoon HK, Kim SW, Kim SJ, Lee KE, et al. Indices of ACTH-stimulated adrenal venous sampling as predictors of postsurgical outcomes in primary aldosteronism. Clin Endocrinol (Oxf). 2022; 96:521–30.

95. Gkaniatsa E, Sakinis A, Palmer M, Muth A, Trimpou P, Ragnarsson O. Adrenal venous sampling in young patients with primary aldosteronism: extravagance or irreplaceable? J Clin Endocrinol Metab. 2021; 106:e2087–95.

96. Dekkers T, Prejbisz A, Kool LJ, Groenewoud HJ, Velema M, Spiering W, et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcomebased randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016; 4:739–46.

97. Deinum J, Prejbisz A, Lenders JW, van der Wilt GJ. Adrenal vein sampling is the preferred method to select patients with primary aldosteronism for adrenalectomy: con side of the argument. Hypertension. 2018; 71:10–4.

98. Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, et al. Evaluation of the sensitivity and specificity of (11) C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn’s adenomas. J Clin Endocrinol Metab. 2012; 97:100–9.

99. Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, et al. Targeting CXCR4 (CXC chemokine receptor type 4) for molecular imaging of aldosterone-producing adenoma. Hypertension. 2018; 71:317–25.

100. Abe T, Naruse M, Young WF Jr, Kobashi N, Doi Y, Izawa A, et al. A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism. J Clin Endocrinol Metab. 2016; 101:1008–15.

101. Hennings J, Sundin A, Hagg A, Hellman P. 11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism. Langenbecks Arch Surg. 2010; 395:963–7.

102. Mendichovszky IA, Powlson AS, Manavaki R, Aigbirhio FI, Cheow H, Buscombe JR, et al. Targeted molecular imaging in adrenal disease: an emerging role for metomidate PET-CT. Diagnostics (Basel). 2016; 6:42.

103. Ding J, Zhang Y, Wen J, Zhang H, Wang H, Luo Y, et al. Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism. Eur J Nucl Med Mol Imaging. 2020; 47:2656–65.

104. Ahn CH, Kim JH. Best achievements in pituitary and adrenal diseases in 2020. Endocrinol Metab (Seoul). 2021; 36:51–6.

105. Ku EJ, Lee C, Shim J, Lee S, Kim KA, Kim SW, et al. Metabolic subtyping of adrenal tumors: prospective multi-center cohort study in Korea. Endocrinol Metab (Seoul). 2021; 36:1131–41.

106. Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens. 2012; 26:281–7.

107. Kwak MK, Lee JY, Kim BJ, Lee SH, Koh JM. Effects of primary aldosteronism and different therapeutic modalities on glucose metabolism. J Clin Med. 2019; 8:2194.

108. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005; 45:1243–8.

109. Halimi JM, Mimran A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension. J Hypertens. 1995; 13(12 Pt 2):1801–2.

110. Monticone S, Sconfienza E, D’Ascenzo F, Buffolo F, Satoh F, Sechi LA, et al. Renal damage in primary aldosteronism: a systematic review and meta-analysis. J Hypertens. 2020; 38:3–12.

111. Kim BJ, Kwak MK, Ahn SH, Kim H, Lee SH, Koh JM. Lower trabecular bone score in patients with primary aldosteronism: human skeletal deterioration by aldosterone excess. J Clin Endocrinol Metab. 2018; 103:615–21.

112. Notsu M, Yamauchi M, Yamamoto M, Nawata K, Sugimoto T. Primary aldosteronism as a risk factor for vertebral fracture. J Clin Endocrinol Metab. 2017; 102:1237–43.

113. Stowasser M, Sharman J, Leano R, Gordon RD, Ward G, Cowley D, et al. Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I. J Clin Endocrinol Metab. 2005; 90:5070–6.

114. Rossi GP, Bolognesi M, Rizzoni D, Seccia TM, Piva A, Porteri E, et al. Vascular remodeling and duration of hypertension predict outcome of adrenalectomy in primary aldosteronism patients. Hypertension. 2008; 51:1366–71.

115. Miyake Y, Tanaka K, Nishikawa T, Naruse M, Takayanagi R, Sasano H, et al. Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study. Endocr J. 2014; 61:35–40.

116. Rossi GP, Rossitto G, Amar L, Azizi M, Riester A, Reincke M, et al. Clinical outcomes of 1625 patients with primary aldosteronism subtyped with adrenal vein sampling. Hypertension. 2019; 74:800–8.

117. Sukor N, Kogovsek C, Gordon RD, Robson D, Stowasser M. Improved quality of life, blood pressure, and biochemical status following laparoscopic adrenalectomy for unilateral primary aldosteronism. J Clin Endocrinol Metab. 2010; 95:1360–4.

118. Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med. 2008; 168:80–5.

119. Giacchetti G, Ronconi V, Turchi F, Agostinelli L, Mantero F, Rilli S, et al. Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J Hypertens. 2007; 25:177–86.

120. Park BK, Fujimori M, Shen SH, Pua U. Asian conference on tumor ablation guidelines for adrenal tumor ablation. Endocrinol Metab (Seoul). 2021; 36:553–63.

121. Park BK. Percutaneous adrenal radiofrequency ablation: a short review for endocrinologists. Endocrinol Metab (Seoul). 2020; 35:750–5.

122. Gomez-Sanchez CE, Qi X, Velarde-Miranda C, Plonczynski MW, Parker CR, Rainey W, et al. Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Mol Cell Endocrinol. 2014; 383:111–7.

123. Ahn CH, Na HY, Park SY, Yu HW, Kim SJ, Choi JY, et al. Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism. Clin Endocrinol (Oxf). 2022; 96:30–9.

124. Williams TA, Gomez-Sanchez CE, Rainey WE, Giordano TJ, Lam AK, Marker A, et al. International histopathology consensus for unilateral primary aldosteronism. J Clin Endocrinol Metab. 2021; 106:42–54.

125. Meyer LS, Handgriff L, Lim JS, Udager AM, Kinker IS, Ladurner R, et al. Single-center prospective cohort study on the histopathology, genotype, and postsurgical outcomes of patients with primary aldosteronism. Hypertension. 2021; 78:738–46.

126. Ohno Y, Sone M, Inagaki N, Yamasaki T, Ogawa O, Takeda Y, et al. Prevalence of cardiovascular disease and its risk factors in primary aldosteronism: a multicenter study in Japan. Hypertension. 2018; 71:530–7.

127. Heinrich DA, Adolf C, Rump LC, Quack I, Quinkler M, Hahner S, et al. Primary aldosteronism: key characteristics at diagnosis: a trend toward milder forms. Eur J Endocrinol. 2018; 178:605–11.

128. Shariq OA, Bancos I, Cronin PA, Farley DR, Richards ML, Thompson GB, et al. Contralateral suppression of aldosterone at adrenal venous sampling predicts hyperkalemia following adrenalectomy for primary aldosteronism. Surgery. 2018; 163:183–90.

129. Wada N, Shibayama Y, Umakoshi H, Ichijo T, Fujii Y, Kamemura K, et al. Hyperkalemia in both surgically and medically treated patients with primary aldosteronism. J Hum Hypertens. 2017; 31:627–32.

130. Mattsson C, Young WF Jr. Primary aldosteronism: diagnostic and treatment strategies. Nat Clin Pract Nephrol. 2006; 2:198–208.

131. Fischer E, Hanslik G, Pallauf A, Degenhart C, Linsenmaier U, Beuschlein F, et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab. 2012; 97:3965–73.

132. Kobayashi H, Abe M, Nakamura Y, Takahashi K, Fujita M, Takeda Y, et al. Association between acute fall in estimated glomerular filtration rate after treatment for primary aldosteronism and long-term decline in renal function. Hypertension. 2019; 74:630–8.

133. Saiki A, Otsuki M, Tamada D, Kitamura T, Mukai K, Yamamoto K, et al. Increased dosage of MRA improves BP and urinary albumin excretion in primary aldosteronism with suppressed plasma renin. J Endocr Soc. 2021; 6:bvab174.

134. Lim PO, Jung RT, MacDonald TM. Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study. Br J Clin Pharmacol. 1999; 48:756–60.

135. Sechi LA, Colussi GL, Novello M, Uzzau A, Catena C. Mineralocorticoid receptor antagonists and clinical outcomes in primary aldosteronism: as good as surgery? Horm Metab Res. 2015; 47:1000–6.

136. Lainscak M, Pelliccia F, Rosano G, Vitale C, Schiariti M, Greco C, et al. Safety profile of mineralocorticoid receptor antagonists: spironolactone and eplerenone. Int J Cardiol. 2015; 200:25–9.

137. de Gasparo M, Joss U, Ramjoue HP, Whitebread SE, Haenni H, Schenkel L, et al. Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther. 1987; 240:650–6.

138. Parthasarathy HK, Menard J, White WB, Young WF Jr, Williams GH, Williams B, 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; 29:980–90.

139. Hood SJ, Taylor KP, Ashby MJ, Brown MJ. The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. Circulation. 2007; 116:268–75.

140. Cohen JB, Bancos I, Brown JM, Sarathy H, Turcu AF, Cohen DL. Primary aldosteronism and the role of mineralocorticoid receptor antagonists for the heart and kidneys. Annu Rev Med. 2023; 74:217–30.

141. Satoh F, Ito S, Itoh H, Rakugi H, Shibata H, Ichihara A, et al. Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism. Hypertens Res. 2021; 44:464–72.

142. Freeman MW, Halvorsen YD, Marshall W, Pater M, Isaacsohn J, Pearce C, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med. 2023; 388:395–405.

143. Affinati AH, Auchus RJ. Endocrine causes of hypertension in pregnancy. Gland Surg. 2020; 9:69–79.

144. Brown CM, Garovic VD. Drug treatment of hypertension in pregnancy. Drugs. 2014; 74:283–96.

145. Garovic VD, Dechend R, Easterling T, Karumanchi SA, McMurtry Baird S, Magee LA, et al. Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association. Hypertension. 2022; 79:e21–41.

146. Forestiero V, Sconfienza E, Mulatero P, Monticone S. Primary aldosteronism in pregnancy. Rev Endocr Metab Disord. 2023; 24:39–48.

147. Rossitto G, Amar L, Azizi M, Riester A, Reincke M, Degenhart C, et al. Subtyping of primary aldosteronism in the AVIS-2 Study: assessment of selectivity and lateralization. J Clin Endocrinol Metab. 2020; 105:dgz017.

148. Zhou Y, Zhang M, Ke S, Liu L. Hypertension outcomes of adrenalectomy in patients with primary aldosteronism: a systematic review and meta-analysis. BMC Endocr Disord. 2017; 17:61.

149. Burrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, et al. The primary aldosteronism surgical outcome score for the prediction of clinical outcomes after adrenalectomy for unilateral primary aldosteronism. Ann Surg. 2020; 272:1125–32.

150. Kim JH, Ahn CH, Kim SJ, Lee KE, Kim JW, Yoon HK, et al. Outcome-based decision-making algorithm for treating patients with primary aldosteronism. Endocrinol Metab (Seoul). 2022; 37:369–82.

151. Kim KJ, Hong N, Yu MH, Lee H, Lee S, Lim JS, et al. Timedependent risk of atrial fibrillation in patients with primary aldosteronism after medical or surgical treatment initiation. Hypertension. 2021; 77:1964–73.