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Primary Aldosteronism

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Secondary Hypertension

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

Abstract

Primary aldosteronism (PA) is a common form of curable arterial hypertension that, when not diagnosed timely, exposes patients to the detrimental effects of hyperaldosteronism for their lifetime. This damages their heart, blood vessels, and kidneys, thus causing cardiovascular events in excess of what expected on the basis of blood pressure elevation. Adrenal vein sampling (AVS)-guided adrenalectomy corrects the hyperaldosteronism and the hypokalemia, in practically all cases, and ameliorates the control of hypertension and/or often resolves it, even when the high blood pressure values were resistant to drug treatment. Likewise, the latter goals can be achieved with a targeted medical treatment. Accordingly, broad strategies to screen early hypertensive patients for PA by means of a simplified diagnostic algorithm and an aggressive diagnostic approach are justified to identify cases of PA that are surgically curable, particularly in patients at high cardiovascular risk.

As imaging is inadequate for subtyping, AVS remains necessary in the work-up of surgically correctable PA. However, it represents the bottleneck, being technically challenging and successfully performed and interpreted only in experienced tertiary referral centers that, unfortunately, are rare. This calls for measures aimed to promote expertise in performing AVS and also to discover alternative techniques for subtyping. The importance of these actions is further emphasized by recent data that showed that AVS-guided adrenalectomy provides biochemical cure in about 98% of the cases, and cure, or a marked improvement, of high blood pressure control in over 80% of the cases. For the PA patients without indication to adrenalectomy, drug treatment is necessary. Follow-up is recommended in all PA patients to ascertain outcomes, recurrences, and the rare development of aldosterone-producing carcinoma.

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References

  1. Rossi GP, Pessina AC, Heagerty AM. Primary aldosteronism: an update on screening, diagnosis and treatment. J Hypertens. 2008;26:613–21.

    CAS  PubMed  Google Scholar 

  2. Rossi GP. New concepts in adrenal vein sampling for aldosterone in the diagnosis of primary aldosteronism. Curr Hypertens Rep. 2007;9:90–7.

    CAS  PubMed  Google Scholar 

  3. Rossi GP. Surgically correctable hypertension caused by primary aldosteronism. Best Pract Res Endocrinol Metab. 2006;20:385–400.

    CAS  Google Scholar 

  4. Rossi GP, Cesari M, Cuspidi C, Maiolino G, Cicala MV, Bisogni V, et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension. 2013;62:62–9.

    CAS  PubMed  Google Scholar 

  5. Fritsch NM, Schiffrin EL, Neves MF, Schiffrin EL. Aldosterone: a risk factor for vascular disease. Curr Hypertens Rep. 2003;5:59–65.

    Google Scholar 

  6. Schupp N, Queisser N, Wolf M, Kolkhof P, Barfacker L, Schafer S, et al. Aldosterone causes DNA strand breaks and chromosomal damage in renal cells, which are prevented by mineralocorticoid receptor antagonists. Horm Metab Res. 2010;42:458–65.

    CAS  PubMed  Google Scholar 

  7. Rocha R, Stier CT Jr, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000;141:3871–8.

    CAS  PubMed  Google Scholar 

  8. Gerling IC, Sun Y, Ahokas RA, Wodi LA, Bhattacharya SK, Warrington KJ, et al. Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype. Am J Physiol Heart Circ Physiol. 2003;285:H813–21.

    CAS  PubMed  Google Scholar 

  9. Weber KT, Brilla CG, Campbell SE, Reddy HK. Myocardial fibrosis and the concepts of cardioprotection and cardioreparation. J Hypertens Suppl. 1992;10:S87–94.

    CAS  PubMed  Google Scholar 

  10. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48:2293–300.

    CAS  PubMed  Google Scholar 

  11. Mulatero P, Monticone S, Burrello J, Veglio F, Williams TA, Funder J. Guidelines for primary aldosteronism: uptake by primary care physicians. J Hypertens. 2016;34:2253–7.

    CAS  PubMed  Google Scholar 

  12. 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.

    PubMed  Google Scholar 

  13. Rossi GP. Primary aldosteronism: a needle in a haystack or a yellow cab on fifth avenue? Curr Hypertens Rep. 2004;6:1–4.

    PubMed  Google Scholar 

  14. Maiolino G, Calò LA, Rossi GP. The time has come for systematic screening for primary aldosteronism in all hypertensives. J Am Coll Cardiol. 2017;69:1821–3.

    PubMed  Google Scholar 

  15. Rossi GP, Gioco F, Fassina A, Gomez-Sanchez CE. Normoaldosteronemic aldosterone-producing adenoma: immunochemical characterization and diagnostic implications. J Hypertens. 2015;33:2546–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 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.

    CAS  PubMed  Google Scholar 

  17. Tu W, Eckert GJ, Hannon TS, Liu H, Pratt LM, Wagner MA, et al. Renin-angiotensin-aldosterone system racial differences in sensitivity of blood pressure to aldosterone. Hypertension. 2014;63:1212–8.

    Google Scholar 

  18. Funder JW. Sensitivity to aldosterone. Hypertension. 2014;63:1168–70.

    Google Scholar 

  19. Rossi GP, Seccia TM, Pessina AC. Clinical use of laboratory tests for the identification of secondary forms of arterial hypertension. Crit Rev Clin Lab Sci. 2007;44:1–85.

    CAS  PubMed  Google Scholar 

  20. Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-himmelfarb CR, et al. Resistant hypertension: detection, evaluation, and management a scientific statement from the American Heart Association. Hypertension. 2018;72:e53–90.

    CAS  PubMed  Google Scholar 

  21. Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.

    PubMed  Google Scholar 

  22. Baudrand R, Guarda FJ, Fardella C, Hundemer G, Brown J, Williams G, et al. Primary aldosteronism continuum of renin-independent aldosteronism in normotension. Hypertension. 2017;68:950–7.

    Google Scholar 

  23. Rossi GP, Sacchetto A, Pavan E, Palatini P, Graniero GR, Canali C, et al. Remodeling of the left ventricle in primary aldosteronism due to Conn’s adenoma. Circulation. 1997;95:1471–8.

    CAS  PubMed  Google Scholar 

  24. 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.

    CAS  PubMed  Google Scholar 

  25. Wu VC, Wang SM, Chang CH, Hu YH, Lin LY, Lin YH, et al. Long term outcome of aldosteronism after target treatments. Sci Rep. 2016;6:32103.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018;6:51–9.

    PubMed  Google Scholar 

  27. Rossi GP, Maiolino G, Flego A, Belfiore A, Bernini G, Fabris B, et al. Adrenalectomy lowers incident atrial fibrillation in primary aldosteronism patients at long term. Hypertension. 2018;71:585–91.

    Google Scholar 

  28. 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.

    CAS  PubMed  Google Scholar 

  29. Rossi GP, Seccia TM, Palumbo G, Belfiore A, Bernini G, Caridi G, et al. Within-patient reproducibility of the aldosterone:renin ratio in primary aldosteronism. Hypertension. 2010;55:83–9.

    CAS  PubMed  Google Scholar 

  30. Rossi GP, Barisa M, Belfiore A, Desideri G, Ferri C, Letizia C, et al. The aldosterone-renin ratio based on the plasma renin activity and the direct renin assay for diagnosing aldosterone-producing adenoma. J Hypertens. 2010;28:1892–9.

    CAS  PubMed  Google Scholar 

  31. Rossi GP. A comprehensive review of the clinical aspects of primary aldosteronism. Nat Rev Endocrinol. 2011;7:485–95.

    PubMed  Google Scholar 

  32. 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.

    PubMed  PubMed Central  Google Scholar 

  33. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527.

    PubMed  PubMed Central  Google Scholar 

  34. 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.

    Google Scholar 

  35. Rossi GP, Rossi E, Pavan E, Rosati N, Zecchel R, Semplicini A, et al. Screening for primary aldosteronism with a logistic multivariate discriminant analysis. Clin Endocrinol. 1998;49:713–23.

    CAS  Google Scholar 

  36. Lazzarini N, Nanni L, Fantozzi C, Pietracaprina A, Pucci G, Seccia TM, et al. Heterogeneous machine learning system for improving the diagnosis of primary aldosteronism. Pattern Recogn Lett. 2015;65:124–30.

    Google Scholar 

  37. Rossi GP, Bisogni V. A useful tool to improve the case detection rate of primary aldosteronism: the aldosterone-renin ratio (ARR)-app. J Hypertens. 2016;34:1019–21.

    CAS  PubMed  Google Scholar 

  38. Opocher G, Rocco S, Murgia A, Mantero F. Effect of verapamil on aldosterone secretion in primary aldosteronism. J Endocrinol Investig. 1987;10:491–4.

    CAS  Google Scholar 

  39. Rossitto G, Cesari M, Ceolotto G, Maiolino G, Maria T, Rossi GP, et al. Effects of mineralocorticoid and AT-1 receptor antagonism on the aldosterone–renin ratio (ARR) in primary aldosteronism patients (EMIRA study): rationale and design. J Hum Hypertens. 2018;33:167–71.

    PubMed  Google Scholar 

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

    Google Scholar 

  41. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. 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;386:2059–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Bazoukis G, Thomopoulos C, Tsioufis C. Effect of MRAs on blood pressure lowering: overview and meta-analysis of randomized controlled trials in hypertension. J Hypertens. 2018;36:987–94.

    CAS  PubMed  Google Scholar 

  43. Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C, et al. Comparison of the captopril and the saline infusion test for excluding aldosterone-producing adenoma. Hypertension. 2007;50:424–31.

    CAS  PubMed  Google Scholar 

  44. Streeten DH, Tomycz N, Anderson GH. Reliability of screening methods for the diagnosis of primary aldosteronism. Am J Med. 1979;67:403–13.

    CAS  PubMed  Google Scholar 

  45. Holland OB, Brown H, Kuhnert L, Fairchild C, Risk M, Gomez-Sanchez CE. Further evaluation of saline infusion for the diagnosis of primary aldosteronism. Hypertension. 1984;6:717–23.

    CAS  PubMed  Google Scholar 

  46. Vanderriele P, Caroccia B, Seccia TM, Piazza M, Lenzini L, Torresan F, et al. The angiotensin type 2 receptor in the human adrenocortical zona glomerulosa and in aldosterone-producing adenoma: low expression and no functional role. Clin Sci. 2018;132:627–40.

    CAS  Google Scholar 

  47. Irony I, Kater CE, Biglieri EG, Shackleton CH. Correctable subsets of primary aldosteronism. Primary adrenal hyperplasia and renin responsive adenoma. Am J Hypertens. 1990;3:576–82.

    CAS  PubMed  Google Scholar 

  48. Gordon RD, Hamlet SM, Tunny TJ, Gomez-Sanchez CE, Jayasinghe LS. Distinguishing aldosterone-producing adenoma from other forms of hyperaldosteronism and lateralizing the tumor pre-operatively. Clin Exp Pharmacol Physiol. 1986;13:325–8.

    CAS  PubMed  Google Scholar 

  49. Phillips JL, Walther MM, Pezzullo JC, Rayford W, Choyke PL, Berman AA, et al. Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma. J Clin Endocrinol Metab. 2000;85:4526–33.

    CAS  PubMed  Google Scholar 

  50. Rossi GP, Seccia TM, Pessina AC. Adrenal gland: a diagnostic algorithm—the holy grail of primary aldosteronism. Nat Rev Endocrinol. 2011;7:697–9.

    Google Scholar 

  51. Thompson GB, Young WF Jr. Adrenal incidentaloma. Curr Opin Oncol. 2003;15:84–90.

    PubMed  Google Scholar 

  52. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000;85:637–44.

    CAS  PubMed  Google Scholar 

  53. Seccia TM, Fassina A, Nussdorfer GG, Pessina AC, Rossi GP. Aldosterone-producing adrenocortical carcinoma: an unusual cause of Conn’s syndrome with an ominous clinical course. Endocr Relat Cancer. 2005;12:149–59.

    PubMed  Google Scholar 

  54. 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.

    PubMed  Google Scholar 

  55. Kempers MJE, Lenders JWM, Van Outheusden L, Van Der Wilt GJ. Diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2017;151:329–38.

    Google Scholar 

  56. Lim V, Guo Q, Grant CS, Thompson GB, Richards ML, Farley DR, et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab. 2014;99:2712–9.

    CAS  PubMed  Google Scholar 

  57. 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.

    PubMed  Google Scholar 

  58. Rossi GP. Update in adrenal venous sampling for primary aldosteronism. Curr Opin Endocrinol Diabetes Obes. 2018;25:160–71.

    CAS  PubMed  Google Scholar 

  59. Rossi GP, Mulatero P, Satoh F. 10 Good reasons why adrenal vein sampling is the preferred method for referring primary aldosteronism patients for adrenalectomy. J Hypertens. 2019;37:603–11.

    Google Scholar 

  60. 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.

    CAS  PubMed  Google Scholar 

  61. Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, 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;8587:1–11.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  63. 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.

    CAS  PubMed  Google Scholar 

  64. Rossitto G, Amar L, Azizi M, Riester A, Degenhart C, Jr, Widimsky J, et al. Subtyping of primary aldosteronism in the AVIS-2 study: assessment of selectivity and lateralisation. J Clin Endocrinol Metab. 2020;105:dgz017.

    Google Scholar 

  65. Miotto D, De Toni R, Pitter G, Seccia TM, Motta R, Vincenzi M, et al. Impact of accessory hepatic veins on adrenal vein sampling for identification of surgically curable primary aldosteronism. Hypertension. 2009;54:885–9.

    CAS  PubMed  Google Scholar 

  66. Yoneda T, Karashima S, Kometani M, Usukura M, Demura M, Sanada J, et al. Impact of new quick gold nanoparticle-based cortisol assay during adrenal vein sampling for primary aldosteronism. J Clin Endocrinol Metab. 2016;101:2554–61.

    CAS  PubMed  Google Scholar 

  67. Georgiades C, Kharlip J, Valdeig S, Wacker FK, Hong K. Use of C-arm CT for improving the hit rate for selective blood sampling from adrenal veins. Radiologe. 2009;49:848–51.

    CAS  PubMed  Google Scholar 

  68. Dekkers T, Deinum J, Schultzekool LJ, Blondin D, Vonend O, Hermus ARRM, et al. Plasma metanephrine and adrenal venous sampling plasma metanephrine for assessing the selectivity of adrenal venous sampling. Hypertension. 2013;62:1152–257.

    CAS  PubMed  Google Scholar 

  69. 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.

    CAS  PubMed  Google Scholar 

  70. Makita K, Nishimoto K, Kiriyama-kitamoto K, Karashima S, Seki T, Yasuda M, et al. A novel method: super-selective adrenal venous sampling. J Vis Exp. 2017;2:1–11.

    Google Scholar 

  71. Ceolotto G, Antonelli G, Maiolino G, Cesari M, Rossitto G, Bisogni V, et al. Androstenedione and 17-α-hydroxyprogesterone are better indicators of adrenal vein sampling selectivity than cortisol. Hypertension. 2017;70:342–6.

    CAS  PubMed  Google Scholar 

  72. 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 outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016;4:739–46.

    PubMed  Google Scholar 

  73. Rossi GP, Funder JW. Adrenal venous sampling versus computed tomographic scan to determine treatment in primary aldosteronism (The SPARTACUS Trial). Hypertension. 2017;69:396–7.

    Google Scholar 

  74. Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2018;285:128–48.

    Google Scholar 

  75. Kupers EM, Amar L, Raynaud A, Plouin PF, Steichen O. A clinical prediction score to diagnose unilateral primary aldosteronism. J Clin Endocrinol Metab. 2012;97:3530–7.

    CAS  PubMed  Google Scholar 

  76. Sze WCC, Soh LM, Lau JH, Reznek R, Sahdev A, Matson M, et al. Diagnosing unilateral primary aldosteronism—comparison of a clinical prediction score, computed tomography and adrenal venous sampling. Clin Endocrinol. 2014;81:25–30.

    Google Scholar 

  77. Aronova A, Iii TJ, Zarnegar R. Management of hypertension in primary aldosteronism. World J Cardiol. 2014;6:227–33.

    PubMed  PubMed Central  Google Scholar 

  78. Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, et al. (PET)—CT for lateralizing aldosterone secretion by Conn’s adenomas. J Clin Endocrinol Metab. 2012;97:100–9.

    CAS  PubMed  Google Scholar 

  79. Joyce MB, Powlson AS, Browne D, Sullivan GJO, Shea PMO, Donoghue DO, et al. 11C—metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice. Clin Endocrinol. 2019;90:670–9.

    Google Scholar 

  80. Ouyang J, Hardy R, Brown M, Helliwell T, Gurnell M, Cuthbertson DJ. 11C-metomidate PET-CT scanning can identify aldosterone-producing adenomas after unsuccessful lateralisation with CT/MRI and adrenal venous sampling. J Hum Hypertens. 2017;31:483–4.

    CAS  PubMed  Google Scholar 

  81. Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, 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;5:689–99.

    PubMed  PubMed Central  Google Scholar 

  82. Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 1992;355:262–5.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Reimer EN, Walenda G, Seidel E, Scholl UI. CACNA1H(M1549V) mutant calcium channel causes autonomous aldosterone production in HAC15 cells and is inhibited by Mibefradil. Endocrinology. 2016;157:3016–22.

    CAS  PubMed  Google Scholar 

  85. Scholl UI, Stölting 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 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, 444e1–2.

    CAS  PubMed  Google Scholar 

  87. Lenzini L, Prisco S, Caroccia B, Rossi GP. Saga of familial hyperaldosteronism: yet a new channel. Hypertension. 2018;71:1010–4.

    CAS  PubMed  Google Scholar 

  88. Rossi GP, Maiolino G, Seccia TM. Adrenal venous sampling: where do we stand? Endocrinol Metab Clin NA. 2019;48:843–58.

    Article  Google Scholar 

  89. Scholl UI, Abriola L, Zhang C, Reimer EN, Plummer M, Kazmierczak BI, et al. Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma. J Clin Invest. 2017;127:2739–50.

    PubMed  PubMed Central  Google Scholar 

  90. Caroccia B, Prisco S, Seccia TM, Piazza M, Maiolino G, Rossi GP. Macrolides blunt aldosterone biosynthesis: a proof-of-concept study in KCNJ5 mutated adenoma cells ex vivo. Hypertension. 2017;70:1238–42.

    CAS  PubMed  Google Scholar 

  91. Maiolino G, Ceolotto G, Battistel M, Barbiero G, Cesari M, Amar L, et al. Macrolides for KCNJ5-mutated aldosterone-producing adenoma (MAPA): design of a study for personalized diagnosis of primary aldosteronism. Blood Press. 2018;27:200–5.

    CAS  PubMed  Google Scholar 

  92. Iacobone M, Mantero F, Basso SM, Lumachi F, Favia G. Results and long-term follow-up after unilateral adrenalectomy for ACTH-independent hypercortisolism in a series of fifty patients. J Endocrinol Investig. 2005;28:327–32.

    CAS  Google Scholar 

  93. Talutis SD, Mcaneny DB, Mcmanus C, Lee JA, Grant SB, Grogan RH, et al. Clinical outcomes after unilateral adrenalectomy for primary aldosteronism. JAMA Surg. 2019;154:1–10.

    Google Scholar 

  94. Citton M, Viel G, Rossi GP, Mantero F, Nitti D, Iacobone M. Outcome of surgical treatment of primary aldosteronism. Langenbeck’s Arch Surg. 2015;400:325–31.

    Google Scholar 

  95. Francesca T, Silvia L, Valeria B, Giuseppe M, Maurizio C, Giacomo R, et al. Drug-resistant hypertension resolution by adrenal vein sampling-guided adrenalectomy. Hypertension. 2019;submitted.

    Google Scholar 

  96. 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.

    CAS  PubMed  Google Scholar 

  97. Citton M, Viel G, Torresan F, Rossi GP, Iacobone M. Effect of unilateral adrenalectomy on the quality of life of patients with lateralized primary aldosteronism. BMC Surg. 2019;18:4–10.

    Google Scholar 

  98. Rossi GP, Rossitto G, Amar L T. The outcomes of subtyped primary aldosteronism patients in the AVIS-2 study. submitted.

    Google Scholar 

  99. Brunaud L, Germain A, Zarnegar R, Cuny T, Ayav A, Bresler L. Robot-assisted adrenalectomy. Surg Laparosc Endosc Percutaneous Tech. 2011;21:248–54.

    Google Scholar 

  100. Fu B, Zhang X, Wang G, Lang B, Ma X, Li H, et al. Long-term results of a prospective, randomized trial comparing retroperitoneoscopic partial versus total adrenalectomy for aldosterone producing adenoma. J Urol. 2011;185:1578–82.

    PubMed  Google Scholar 

  101. Proye CA, Mulliez EA, Carnaille BM, Lecomte-Houcke M, Decoulx M, Wemeau JL, et al. Essential hypertension: first reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism? Surgery. 1998;124:1128–33.

    CAS  PubMed  Google Scholar 

  102. Zarnegar R, Young WF, Lee J, Sweet MP, Kebebew E, Farley DR, et al. The aldosteronoma resolution score. Ann Surg. 2008;247:511–8.

    PubMed  Google Scholar 

  103. 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.

    CAS  PubMed  Google Scholar 

  104. Obara T, Ito Y, Okamoto T, Kanaji Y, Yamashita T, Aiba M, et al. Risk factors associated with postoperative persistent hypertension in patients with primary aldosteronism. Surgery. 1992;112:987–93.

    CAS  PubMed  Google Scholar 

  105. Capelli I, Gasperoni L, Ruggeri M, Donati G, Baraldi O, Sorrenti G, et al. New mineralocorticoid receptor antagonists: update on their use in chronic kidney disease and heart failure. J Nephrol. 2019;33:37–48.

    PubMed  Google Scholar 

  106. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, et al. A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008;51:742–8.

    CAS  PubMed  Google Scholar 

  108. Bramlage P, Swift SL, Thoenes M, Minguet J, Ferrero C, Schmieder RE. Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease. Eur J Heart Fail. 2016;18:28–37.

    CAS  PubMed  Google Scholar 

  109. Amar L, Azizi M, Menard J, Peyrard S, Watson C, Plouin PF. Aldosterone synthase inhibition with LCI699. Hypertension. 2010;56:831–8.

    CAS  PubMed  Google Scholar 

  110. Meguro M, Miyauchi S, Kanao Y, Naito S, Suzuki K, Inoue S, et al. 4-Anilino-pyrimidine, novel aldosterone synthase (CYP11B2) inhibitors bearing pyrimidine structures. Bioorg Med Chem Lett. 2017;27:1902–6.

    Google Scholar 

  111. Sparks SM, Danger DP, Hoekstra WJ, Leesnitzer T, Schotzinger RJ, Yates CM, et al. Development of highly selective pyrimidine-based aldosterone synthase (CYP11B2) inhibitors. ACS Med Chem Lett. 2019;10:1056–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Akram M, Waratchareeyakul W, Haupenthal J, Hartmann RW, Schuster D. Pharmacophore modeling and in silico/in vitro screening for human cytochrome P450 11B1 and cytochrome P450 11B2 inhibitors. Front Chem. 2017;5:104.

    Google Scholar 

  113. Seccia TM, Caroccia B, Gomez-Sanchez EP, Vanderriele PE, Gomez-Sanchez CE, Rossi GP. Review of markers of zona glomerulosa and aldosterone-producing adenoma cells. Hypertension. 2017;70:867–74.

    CAS  PubMed  Google Scholar 

  114. Rossi GP, Vendraminelli R, Cesari M, Pessina AC. A thoracic mass with hypertension and hypokalaemia. Lancet. 2000;356:1570.

    CAS  PubMed  Google Scholar 

  115. Iwakura Y, Morimoto R, Kudo M, Ono Y, Takase K, Seiji K, et al. Predictors of decreasing glomerular filtration rate and prevalence of chronic kidney disease after treatment of primary aldosteronism: renal outcome of 213 cases. J Clin Endocrinol Metab. 2014;99:1593–8.

    CAS  PubMed  Google Scholar 

  116. Hall JE, Granger JP, Smith MJ Jr, Premen AJ. Role of renal hemodynamics and arterial pressure in aldosterone “escape”. Hypertension. 1984;6:I183–92.

    CAS  PubMed  Google Scholar 

  117. Conn JW, Louis LH. Primary aldosteronism, a new clinical entity. Ann Intern Med. 1956;44:1–15.

    CAS  PubMed  Google Scholar 

  118. 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.

    PubMed  Google Scholar 

  119. Haase M, Riester A, Kröpil 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.

    CAS  PubMed  Google Scholar 

  120. Fontes RG, Kater CE, Biglieri EG, Irony I. Reassessment of the predictive value of the postural stimulation test in primary aldosteronism. Am J Hypertens. 1991;4:786–91.

    Google Scholar 

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Acknowledgments

The studies herein reported were mostly supported by research grants from the EU COST-ADMIRE BM1301 and ENSAT-HT 633983, FORICA (The Foundation for Advanced Research in Hypertension and Cardiovascular Diseases) and the Società Italiana dell’Ipertensione Arteriosa and The University of Padua.

Highlights

  • PA is a common curable cause of hypertension and is associated with increased cardiovascular events.

  • Newly diagnosed hypertensive patients should be tested for PA even when normokalemic.

  • Case detection testing for PA should be performed by measuring the aldosterone–renin ratio.

  • Strategies for improving subtyping of PA need to be developed as AVS is not widely available.

Conflict of Interest and Financial Disclosure to be Disclosed

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Authors and Affiliations

  1. Department of Medicine—DIMED—Hypertension Unit and Specialized Center, University of Padova, University Hospital, Padova, Italy

    Gian Paolo Rossi

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  1. Gian Paolo Rossi
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Correspondence to Gian Paolo Rossi .

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Editors and Affiliations

  1. Center of Clinical Physiology and Hypertension, Policlinic Hospital, University of Milan, Milan, Italy

    Alberto Morganti

  2. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Enrico Agabiti Rosei

  3. Department of Medicine, Endocrine Unit, University of Padua, Padova, Italy

    Franco Mantero

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Rossi, G.P. (2020). Primary Aldosteronism. In: Morganti, A., Agabiti Rosei, E., Mantero, F. (eds) Secondary Hypertension . Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-030-45562-0_4

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