Download PDF
Horm Metab Res 2017; 49(03): 151-163
DOI: 10.1055/s-0043-100767
Review
© Georg Thieme Verlag KG Stuttgart · New York

How to Escape from Primary Aldosteronism? News and Views on an Adrenal Disorder of Salt Retention

Holger S. Willenberg
1   Division of Endocrinology and Metabolism, Rostock University Medical Center, Rostock, Germany
› Author Affiliations
Further Information

Publication History

received 12 September 2016

accepted 05 January 2017

Publication Date:
28 March 2017 (online)

Also available at
    Permissions and Reprints

Abstract

The last years have seen substantial progress in primary aldosteronism (PA), which is the most common cause of secondary hypertension. Many programs have been established around the world to meet the needs in healthcare and the management of patients with PA according to published guidelines and clinical protocols. Systematic analysis of emerging data and meticulous scientific work have informed us on the molecular basis of the disease and helped to characterize hereditary forms of PA. Techniques have been developed to better diagnose PA and to establish genotype-phenotype relationships and their impact on hypertension. Studies have been undertaken to stratify patients for risk factors and to ensure quality of best medical treatment. This review focuses on some clinically relevant problems in characterizing autonomous aldosterone secretion and discusses testing and management strategies. Besides, this review puts the emphasis on some colorful studies not to pale soon beside an ever evolving painting background.

Key words

hypertension - adrenal - aldosterone - sodium - cortisol - tumor
 

  • References

  • 1 Catena C, Colussi G, Brosolo G, Novello M, Sechi LA. Aldosterone and left ventricular remodeling. Horm Metab Res 2015; 47: 981-986
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr. WF, Montori VM. Endocrine Society Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281
    CrossrefPubMedGoogle Scholar
  • 3 Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young Jr WF. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916
    CrossrefPubMedGoogle Scholar
  • 4 Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N, Tanabe A. Task force committee on primary aldosteronism, the japan endocrine society guidelines for the diagnosis and treatment of primary aldosteronism – the japan endocrine society. 2009; Endocr J 2011; 58: 711-721
    CrossrefPubMedGoogle Scholar
  • 5 Kuhlmann D, Ragan C, Ferrebee JW, Atchley DW, Loeb RF. Toxic effects of desoxycorticosterone esters in dogs. Science 1939; 90: 496-497
    CrossrefPubMedGoogle Scholar
  • 6 Ragan C, Ferrebee JW, Phyfe P, Atchley DW, Loeb RF. Syndrome of polydipsia and polyuria induced in normal animals by desoxycorticosterone acetate. Am J Physiol 1940; 131: 73-78
    PubMedGoogle Scholar
  • 7 Zierler KL, Lilienthal Jr JL. Sodium loss in man induced by desoxycorticosterone acetate; study in a subject with myotonic dystrophy. Am J Med 1948; 4: 186-192
    CrossrefPubMedGoogle Scholar
  • 8 August JT, Nelson DH, Thorn GW. Response of normal subjects to large amounts of aldosterone. J Clin Invest 1958; 37: 1549-1555
    CrossrefPubMedGoogle Scholar
  • 9 Rovner DR, Conn JW, Knopf RF, Cohen EL, Hsueh MT. Nature of renal escape from the the sodium–retaining effect of aldosterone in primary aldosteronism and in normal subjects. J Clin Endocrinol Metab 1965; 25: 53-64
    CrossrefPubMedGoogle Scholar
  • 10 Titze J, Rakova N, Kopp C, Dahlmann A, Jantsch J, Luft FC. Balancing wobbles in the body sodium. Nephrol Dial Transplant. 2016; 31: 1078-1081
    CrossrefPubMedGoogle Scholar
  • 11 Intengan HD, Park JB, Schiffrin EL. Blood pressure and small arteries in DOCA-salt-treated genetically AVP-deficient rats: role of endothelin. Hypertension 1999; 34: 907-913
    CrossrefPubMedGoogle Scholar
  • 12 Schmale H, Richter D. Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats. Nature 1984; 308: 705-709
    CrossrefPubMedGoogle Scholar
  • 13 Zelena D, Barna I, Csabai K, Orlando GF, Makara GB, Engelmann M. Response of the adrenomedullary system to early postnatal stress in the Brattleboro rat. Ann N Y Acad Sci 2008; 1148: 456-561
    CrossrefPubMedGoogle Scholar
  • 14 Gruber KA. The Brattleboro rat and salt-induced hypertension. Hypertension 1982; 4: 572-574
    CrossrefPubMedGoogle Scholar
  • 15 Joffe HV, Adler GK. Effect of aldosterone and mineralocorticoid receptor blockade on vascular inflammation. Heart Fail Rev 2005; 10: 31-37
    CrossrefPubMedGoogle Scholar
  • 16 Fiebeler A, Muller DN, Shagdarsuren E, Luft FC. Aldosterone, mineralocorticoid receptors, and ascular inflammation. Curr Opin Nephrol Hypertens 2007; 16: 134-142
    PubMedGoogle Scholar
  • 17 Douillard C, Houillier P, Nussberger J, Girerd X. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 2: First diagnostic steps. Ann Endocrinol 2016; 77: 192-201
    CrossrefPubMedGoogle Scholar
  • 18 Burrello J, Monticone S, Tetti M, Rossato D, Versace K, Castellano I, Williams TA, Veglio F, Mulatero P. Subtype diagnosis of primary aldosteronism: Approach to different clinical scenarios. Horm Metab Res 2015; 47: 959-966
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP. Intraadrenal interactions in the regulation of adrenocortical steroidogenesis. Endocr Rev 1998; 19: 101-143
    CrossrefPubMedGoogle Scholar
  • 20 Willenberg HS, Schinner S, Ansurudeen I. New mechanisms to control aldosterone synthesis. Horm Metab Res 2008; 40: 435-441
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Adler GK, Bonyhay I, Curren V, Waring E, Freeman R. Hypoglycaemia increases aldosterone in a dose-dependent fashion. Diabet Med 2010; 27: 1250-1255
    CrossrefPubMedGoogle Scholar
  • 22 Hattangady NG, Olala LO, Bollag WB, Rainey WE. Acute and chronic regulation of aldosterone production. Mol Cell Endocrinol 2012; 350: 151-162
    CrossrefPubMedGoogle Scholar
  • 23 Stowasser M, Ahmed AH, Pimenta E, Taylor PJ, Gordon RD. Factors affecting the aldosterone/renin ratio. Horm Metab Res 2012; 44: 170-176
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Beuschlein F. Regulation of aldosterone secretion: from physiology to disease. Eur J Endocrinol 2013; 168: R85-R93
    CrossrefPubMedGoogle Scholar
  • 25 Ahmed AH, Gordon RD, Ward G, Wolley M, Kogovsek C, Stowasser M. Should aldosterone suppression tests be conducted during a particular phase of the menstrual cycle, and, if so, which phase? Results of a preliminary study. Clin Endocrinol 2015; 83: 203-207
    PubMedGoogle Scholar
  • 26 Schirpenbach C, Seiler L, Maser-Gluth C, Beuschlein F, Reincke M, Bidlingmaier M. Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps. Clin Chem 2006; 52: 1749-1755
    CrossrefPubMedGoogle Scholar
  • 27 Giacchetti G, Ronconi V, Lucarelli G, Boscaro M, Mantero F. Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: need for a standardized protocol. J Hypertens 2006; 24: 737-745
    CrossrefPubMedGoogle Scholar
  • 28 Alvarez-Madrazo S, Padmanabhan S, Mayosi BM, Watkins H, Avery P, Wallace AM, Fraser R, Davies E, Keavney B, Connell JM. Familial and phenotypic associations of the aldosterone Renin ratio. J Clin Endocrinol Metab 2009; 94: 4324-4333
    CrossrefPubMedGoogle Scholar
  • 29 Mulatero P, Monticone S, Bertello C, Mengozzi G, Tizzani D, Iannaccone A, Veglio F. Confirmatory tests in the diagnosis of primary aldosteronism. Horm Metab Res 2010; 42: 406-410
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Haase M, Gruber M, Gao X, Vonend O, Willenberg HS. Confirmatory testing for primary aldosteronism. In: Hellman P. (ed.). Primary Aldosteronism – Molecular Genetics, Endocrinology and Translational Medicine. Berlin: Springer; 2014
    Google Scholar
  • 31 Sabbadin C, Fallo F. Hyperaldosteronism: screening and diagnostic tests. High Blood Press Cardiovasc Prev 2016; 23: 69-72
    CrossrefPubMedGoogle Scholar
  • 32 Baguet JP, Steichen O, Mounier-Véhier C, Gosse P. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA?. Ann Endocrinol 2016; 77: 187-191
    CrossrefPubMedGoogle Scholar
  • 33 Reznik Y, Amar L, Tabarin A. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 3: Confirmatory testing. Ann Endocrinol 2016; 77: 202-207
    CrossrefPubMedGoogle Scholar
  • 34 Funder JW. Primary aldosteronism: new answers, new questions. Horm Metab Res 2015; 47: 935-940
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, Beuschlein F, Reincke M. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol 2004; 150: 329-337
    CrossrefPubMedGoogle Scholar
  • 36 Balaş M, Zosin I, Maser-Gluth C, Hermsen D, Cupisti K, Schott M, Schinner S, Knoefel WT, Scherbaum WA, Willenberg HS. Indicators of mineralocorticoid excess in the evaluation of primary aldosteronism. Hypertens Res 2010; 33: 850-856
    CrossrefPubMedGoogle Scholar
  • 37 Solar M, Malirova E, Ballon M, Pelouch R, Ceral J. Confirmatory testing in primary aldosteronism: extensive medication switching is not needed in all patients. Eur J Endocrinol 2012; 166: 679-686
    CrossrefPubMedGoogle Scholar
  • 38 Haase M, Riester A, Kröpil P, Hahner S, Degenhart C, Willenberg HS, Reincke M. Outcome of adrenal vein sampling performed during concurrent mineralocorticoid receptor antagonist therapy. J Clin Endocrinol Metab 2014; 99: 4397-4402
    CrossrefPubMedGoogle Scholar
  • 39 Grim CE. Evolution of diagnostic criteria for primary aldosteronism: why is it more common in “drug–resistant” hypertension today?. Curr Hypertens Rep 2004; 6: 485-492
    CrossrefPubMedGoogle Scholar
  • 40 Willenberg HS, Vonend O, Schott M, Gao X, Blondin D, Saleh A, Rump LC, Scherbaum WA. Comparison of the saline infusion test and the fludrocortisone suppression test in the diagnosis of primary aldosteronism. Horm Metab Res 2012; 44: 527-532
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Stowasser M, Gordon RD. Primary aldosteronism – careful investigation is essential and rewarding. Mol Cell Endocrinol 2004; 217: 33-39
    CrossrefPubMedGoogle Scholar
  • 42 Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85
    CrossrefPubMedGoogle Scholar
  • 43 Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension 2015; 65: 257-263
    CrossrefPubMedGoogle Scholar
  • 44 Funder JW. Aldosterone, mineralocorticoid receptors and vascular inflammation. Mol Cell Endocrinol 2004; 217: 263-269
    CrossrefPubMedGoogle Scholar
  • 45 Gilbert KC, Brown NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes 2010; 17: 199-204
    CrossrefPubMedGoogle Scholar
  • 46 Petramala L, Iacobellis G, Carnevale R, Marinelli C, Zinnamosca L, Concistrè A, Galassi M, Iannucci G, Lucia P, Pignatelli P, Ciardi A, Violi F, De Toma G, Letizia C. Enhanced soluble serum CD40L and serum P-selectin levels in primary aldosteronism. Horm Metab Res 2016; 48: 440-445
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Findling JW, Raff H. Screening and diagnosis of Cushing’s syndrome. Endocrinol Metab Clin North Am 2005; 34: 385-402
    CrossrefPubMedGoogle Scholar
  • 48 Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
    CrossrefPubMedGoogle Scholar
  • 49 Nieman LK. Cushing’s syndrome: update on signs, symptoms and biochemical screening. Eur J Endocrinol 2015; 173: M33-M38
    CrossrefPubMedGoogle Scholar
  • 50 Conn JW. Primary aldosteronism. J Lab Clin Med 1955; 45: 661-664
    PubMedGoogle Scholar
  • 51 Hiramatsu K, Yamada T, Yukimura Y, Komiya I, Ichikawa K, Ishihara M, Nagata H, Izumiyama T. A screening test to identify aldosterone–producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med 1981; 141: 1589-1593
    CrossrefPubMedGoogle Scholar
  • 52 Weinberger MH, Fineberg NS. The diagnosis of primary aldosteronism and separation of two major subtypes. Arch Intern Med 1993; 153: 2125-2129
    CrossrefPubMedGoogle Scholar
  • 53 Willenberg HS, Kolentini C, Quinkler M, Cupisti K, Krausch M, Schott M, Scherbaum WA. The serum sodium to urinary sodium to (serum potassium)2 to urinary potassium (SUSPPUP) ratio in patients with primary aldosteronism. Eur J Clin Invest 2009; 39: 43-50
    CrossrefPubMedGoogle Scholar
  • 54 Kuo CC, Wu VC, Tsai CW, Huang KH, Wang SM, Li BC, Chang CC, Lu CC, Yang WS, Chao CT, Tsai IC, Lai CF, Lin WC, Wu MS, Lin YH, Lin CY, Chang HW, Wang WJ, Chiang WC, Kao TW, Chueh SC, Chu TS, Tsai TJ, Wu KD. TAIPAI Study Group Combining body mass index and serum potassium to urine potassium clearance ratio is an alternative method to predict primary aldosteronism. Clin Chim Acta 2011; 412: 1637-1642
    CrossrefPubMedGoogle Scholar
  • 55 Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Montemurro D, Palumbo G, Rizzoni D, Rossi E, Semplicini A, Agabiti-Rosei E, Pessina AC, Mantero F. PAPY Study Investigators Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone–producing adenoma. J Hypertens 2007; 25: 1433-1442
    CrossrefPubMedGoogle Scholar
  • 56 Gordon RD. Mineralocorticoid hypertension. Lancet 1994; 344: 240-243
    CrossrefPubMedGoogle Scholar
  • 57 Gouli A, Kaltsas G, Tzonou A, Markou A, Androulakis II, Ragkou D, Vamvakidis K, Zografos G, Kontogeorgos G, Chrousos GP, Piaditis G. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest 2011; 41: 1227-1236
    CrossrefPubMedGoogle Scholar
  • 58 Ahmed AH, Cowley D, Wolley M, Gordon RD, Xu S, Taylor PJ, Stowasser M. Seated saline suppression testing for the diagnosis of primary aldosteronism: a preliminary study. J Clin Endocrinol Metab 2014; 99: 2745-2753
    CrossrefPubMedGoogle Scholar
  • 59 Pappa T, Papanastasiou L, Kaltsas G, Markou A, Tsounas P, Androulakis I, Tsiavos V, Zografos G, Vamvakidis K, Samara C, Piaditis G. Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension. J Clin Endocrinol Metab 2012; 97: E537-E545
    CrossrefPubMedGoogle Scholar
  • 60 Schirpenbach C, Seiler L, Maser-Gluth C, Rüdiger F, Nickel C, Beuschlein F, Reincke M. Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites. Eur J Endocrinol 2006; 154: 865-873
    CrossrefPubMedGoogle Scholar
  • 61 Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young Jr. WF. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89: 1045-1050
    CrossrefPubMedGoogle Scholar
  • 62 Lau JH, Sze WC, Reznek RH, Matson M, Sahdev A, Carpenter R, Berney DM, Akker SA, Chew SL, Grossman AB, Monson JP, Drake WM. A prospective evaluation of postural stimulation testing, computed tomography and adrenal vein sampling in the differential diagnosis of primary aldosteronism. Clin Endocrinol 2012; 76: 182-188
    CrossrefPubMedGoogle Scholar
  • 63 Weickert MO, Schöfl-Siegert B, Arafat AM, Pfeiffer AF, Möhlig M, Schöfl C. A reverse postural test as a screening tool for aldosterone-producing adenoma: a pilot study. Endocrine 2009; 36: 75-82
    CrossrefPubMedGoogle Scholar
  • 64 Moors M, Williams TA, Deinum J, Eisenhofer G, Reincke M, Lenders JW. Steroid hormone production in patients with aldosterone producing adenomas. Horm Metab Res 2015; 47: 967-972
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Dringenberg T, Schwitalla M, Haase M, Scherbaum WA, Willenberg HS. Control of CYP11B2/CYP11B1 expression ratio and consequences for the zonation of the adrenal cortex. Horm Metab Res 2013; 45: 81-85
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Späth M, Korovkin S, Antke C, Anlauf M, Willenberg HS. Aldosterone and cortisol co-secreting adrenal tumors: the lost subtype of primary aldosteronism. Eur J Endocrinol 2011; 164: 447-455
    CrossrefPubMedGoogle Scholar
  • 67 Scholl UI, Healy JM, Thiel A, Fonseca AL, Brown TC, Kunstman JW, Horne MJ, Dietrich D, Riemer J, Kücükköylü S, Reimer EN, Reis AC, Goh G, Kristiansen G, Mahajan A, Korah R, Lifton RP, Prasad ML, Carling T. Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype. Clin Endocrinol 2015; 83: 779-789
    CrossrefPubMedGoogle Scholar
  • 68 Azizan EA, Poulsen H, Tuluc P, Zhou J, Clausen MV, Lieb A, Maniero C, Garg S, Bochukova EG, Zhao W, Shaikh LH, Brighton CA, Teo AE, Davenport AP, Dekkers T, Tops B, Küsters B, Ceral J, Yeo GS, Neogi SG, McFarlane I, Rosenfeld N, Marass F, Hadfield J, Margas W, Chaggar K, Solar M, Deinum J, Dolphin AC, Farooqi IS, Striessnig J, Nissen P, Brown MJ. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet 2013; 45: 1055-1060
    CrossrefPubMedGoogle Scholar
  • 69 Åkerström T, Willenberg HS, Cupisti K, Ip J, Backman S, Moser A, Maharjan R, Robinson B, Iwen KA, Dralle H, DVolpe C, Bäckdahl M, Botling J, Stålberg P, Westin G, Walz MK, Lehnert H, Sidhu S, Zedenius J, Björklund P, Hellman P. Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas. Endocr Relat Cancer 2015; 22: 735-744
    CrossrefPubMedGoogle Scholar
  • 70 Monticone S, Castellano I, Versace K, Lucatello B, Veglio F, Gomez-Sanchez CE, Williams TA, Mulatero P. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone–producing adenomas. Mol Cell Endocrinol 2015; 411: 146-154
    CrossrefPubMedGoogle Scholar
  • 71 Geller DS, Zhang J, Wisgerhof MV, Shackleton C, Kashgarian M, Lifton RP. A novel form of human mendelian hypertension featuring nonglucocorticoid–remediable aldosteronism. J Clin Endocrinol Metab 2008; 93: 3117-3123
    CrossrefPubMedGoogle Scholar
  • 72 Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G, Åkerström G, Wang W, Carling T, Lifton RP. K+ channel mutations in adrenal aldosterone–producing adenomas and hereditary hypertension. Science 2011; 331: 768-772
    CrossrefPubMedGoogle Scholar
  • 73 Scholl UI, Goh G, Stölting G, de Oliveira RC, Choi M, Overton JD, Fonseca AL, Korah R, Starker LF, Kunstman JW, Prasad ML, Hartung EA, Mauras N, Benson MR, Brady T, Shapiro JR, Loring E, Nelson-Williams C, Libutti SK, Mane S, Hellman P, Westin G, Åkerström G, Björklund P, Carling T, Fahlke C, Hidalgo P, Lifton RP. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet 2013; 45: 1050-1054
    CrossrefPubMedGoogle Scholar
  • 74 Scholl UI, Stölting G, Nelson-Williams C, Vichot AA, Choi M, Loring E, Prasad ML, Goh G, Carling T, Juhlin CC, Quack I, Rump LC, Thiel A, Lande M, Frazier BG, Rasoulpour M, Bowlin DL, Sethna CB, Trachtman H, Fahlke C, Lifton RP. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife 2015; 4: e06315
    PubMedGoogle Scholar
  • 75 Scholl UI, Nelson-Williams C, Yue P, Grekin R, Wyatt RJ, Dillon MJ, Couch R, Hammer LK, Harley FL, Farhi A, Wang WH, Lifton RP. Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Proc Natl Acad Sci USA 2012; 109: 2533-2538
    CrossrefPubMedGoogle Scholar
  • 76 Zennaro MC, Fernandes-Rosa F, Boulkroun S, Jeunemaitre X. Bilateral idiopathic adrenal hyperplasia: genetics and beyond. Horm Metab Res 2015; 47: 947-952
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Schinner S, Willenberg HS, Schott M, Scherbaum WA. Pathophysiological aspects of Wnt-signaling in endocrine disease. Eur J Endocrinol 2009; 160: 731-737
    CrossrefPubMedGoogle Scholar
  • 78 Bertagna X. Genetics of adrenal diseases in 2014: Genetics improves understanding of adrenocortical tumours. Nat Rev Endocrinol 2015; 11: 77-78
    PubMedGoogle Scholar
  • 79 Boulkroun S, Fernandes-Rosa FL, Zennaro MC. Molecular and cellular mechanisms of aldosterone producing adenoma development. Front Endocrinol 2015; 6: 95
    CrossrefPubMedGoogle Scholar
  • 80 Zennaro MC, Rickard AJ, Boulkroun S. Genetics of mineralocorticoid excess: an update for clinicians. Eur J Endocrinol 2013; 169: R15-R25
    CrossrefPubMedGoogle Scholar
  • 81 Azizan EA, Brown MJ. Novel genetic determinants of adrenal aldosterone regulation. Curr Opin Endocrinol Diabetes Obes 2016; 23: 209-217
    CrossrefPubMedGoogle Scholar
  • 82 Dutta RK, Söderkvist P, Gimm O. Genetics of primary hyperaldosteronism. Endocr Relat Cancer 2016; 23: R437-R454
    CrossrefPubMedGoogle Scholar
  • 83 Nanba K, Chen AX, Omata K, Vinco M, Giordano TJ, Else T, Hammer GD, Tomlins SA, Rainey WE. Molecular heterogeneity in aldosterone-producing adenomas. J Clin Endocrinol Metab 2016; 101: 999-1007
    CrossrefPubMedGoogle Scholar
  • 84 Dekkers T, ter Meer M, Lenders JW, Hermus AR, Schultze Kool L, Langenhuijsen JF, Nishimoto K, Ogishima T, Mukai K, Azizan EA, Tops B, Deinum J, Küsters B. Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit?. J Clin Endocrinol Metab 2014; 99: E1341-E1351
    CrossrefPubMedGoogle Scholar
  • 85 Korah HE, Scholl UI. An update on familial hyperaldosteronism. Horm Metab Res 2015; 47: 941-946
    Article in Thieme ConnectPubMedGoogle Scholar
  • 86 Zennaro MC, Jeunemaitre X. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism. Ann Endocrinol 2016; 77: 214-219
    CrossrefPubMedGoogle Scholar
  • 87 Fallo F, Bertello C, Tizzani D, Fassina A, Boulkroun S, Sonino N, Monticone S, Viola A, Veglio F, Mulatero P. Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a prospective study. J Hypertens 2011; 29: 1773-1777
    CrossrefPubMedGoogle Scholar
  • 88 Chu MD, Ulick S. Isolation and identification of 18-hydroxycortisol from the urine of patients with primary aldosteronism. J Biol Chem 1982; 257: 2218-2224
    CrossrefPubMedGoogle Scholar
  • 89 Ulick S, Chu MD, Land M. Biosynthesis of 18-oxocortisol by aldosterone-producing adrenal tissue. J Biol Chem 1983; 258: 5498-5502
    PubMedGoogle Scholar
  • 90 Mulatero P, di Cella SM, Monticone S, Schiavone D, Manzo M, Mengozzi G, Rabbia F, Terzolo M, Gomez-Sanchez EP, Gomez-Sanchez CE, Veglio F. 18-Hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes. J Clin Endocrinol Metab 2012; 97: 881-889
    CrossrefPubMedGoogle Scholar
  • 91 Morra di Cella S, Veglio F, Mulatero P, Christensen V, Aycock K, Zhu Z, Gomez-Sanchez EP, Gomez-Sanchez CE. A time-resolved fluoroimmunoassay for 18–oxocortisol and 18–hydroxycortisol. Development of a monoclonal antibody to 18–oxocortisol. J Steroid Biochem Mol Biol 2002; 82: 83-88
    CrossrefPubMedGoogle Scholar
  • 92 Willenberg HS, Späth M, Maser-Gluth C, Engers R, Anlauf M, Dekomien G, Schott M, Schinner S, Cupisti K, Scherbaum WA. Sporadic solitary aldosterone and cortisol co-secreting adenomas – endocrine function tests, histological and genetic findings in a subtype of primary aldosteronism. Hypertens Res 2010; 33: 467-472
    CrossrefPubMedGoogle Scholar
  • 93 Williams TA, Peitzsch M, Dietz AS, Dekkers T, Bidlingmaier M, Riester A, Treitl M, Rhayem Y, Beuschlein F, Lenders JW, Deinum J, Eisenhofer G, Reincke M. Genotype–specific steroid profiles associated with aldosterone–producing adenomas. Hypertension 2016; 67: 139-145
    CrossrefPubMedGoogle Scholar
  • 94 Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Takase K, Seiji K, Sasamoto H, Honma S, Okuyama M, Yamashita K, Gomez-Sanchez CE, Rainey WE, Arai Y, Sasano H, Nakamura Y, Ito S. Measurement of peripheral plasma 18–oxocortisol can discriminate unilateral adenoma from bilateral diseases in patients with primary aldosteronism. Hypertension 2015; 65: 1096-1102
    CrossrefPubMedGoogle Scholar
  • 95 Eisenhofer G, Dekkers T, Peitzsch M, Dietz AS, Bidlingmaier M, Treitl M, Williams TA, Bornstein SR, Haase M, Rump LC, Willenberg HS, Beuschlein F, Deinum J, Lenders JW, Reincke M. Mass spectrometry–based adrenal and peripheral venous steroid profiling for subtyping primary aldosteronism. Clin Chem 2016; 62: 514-524
    CrossrefPubMedGoogle Scholar
  • 96 Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J. Systematic: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med 2009; 151: 329-337
    CrossrefPubMedGoogle Scholar
  • 97 Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young Jr. WF. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 63: 151-160
    CrossrefPubMedGoogle Scholar
  • 98 Mengozzi G, Rossato D, Bertello C, Garrone C, Milan A, Pagni R, Veglio F, Mulatero P. Rapid cortisol assay during adrenal vein sampling in patients with primary aldosteronism. Clin Chem 2007; 53: 1968-1971
    CrossrefPubMedGoogle Scholar
  • 99 Auchus RJ, Michaelis C, Wians Jr FH, Dolmatch BL, Josephs SC, Trimmer CK, Anderson ME, Nwariaku FE. Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg 2009; 249: 318-321
    CrossrefPubMedGoogle Scholar
  • 100 Betz MJ, Degenhart C, Fischer E, Pallauf A, Brand V, Linsenmaier U, Beuschlein F, Bidlingmaier M, Reincke M. Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is useful in centers with low success rates. Eur J Endocrinol 2011; 165: 301-306
    CrossrefPubMedGoogle Scholar
  • 101 Dekkers T, Prejbisz A, Kool LJ, Groenewoud HJ, Velema M, Spiering W, Kołodziejczyk-Kruk S, Arntz M, Kądziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FC, Hermus AR, Januszewicz A, Ligthart-Naber AF, Makai P, van der Wilt GJ, Lenders JW, Deinum J. SPARTACUS Investigators Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739-746
    CrossrefPubMedGoogle Scholar
  • 102 Blondin D, Quack I, Haase M, Kücükköylü S, Willenberg HS. Indication and technical aspects of adrenal blood sampling. Rofo 2015; 187: 19-28
    Article in Thieme ConnectPubMedGoogle Scholar
  • 103 Dekkers T, Deinum J, Schultzekool LJ, Blondin D, Vonend O, Hermus AR, Peitzsch M, Rump LC, Antoch G, Sweep FC, Bornstein SR, Lenders JW, Willenberg HS, Eisenhofer G. Plasma metanephrine for assessing the selectivity of adrenal venous sampling. Hypertension 2013; 62: 1152-1157
    CrossrefPubMedGoogle Scholar
  • 104 Peitzsch M, Dekkers T, Haase M, Sweep FC, Quack I, Antoch G, Siegert G, Lenders JW, Deinum J, Willenberg HS, Eisenhofer G. An LC-MS/MS method for steroid profiling during adrenal venous sampling for investigation of primary aldosteronism. J Steroid Biochem Mol Biol 2015; 145: 75-84
    CrossrefPubMedGoogle Scholar
  • 105 Kem DC, Weinberger MH, Gomez-Sanchez C, Kramer NJ, Lerman R, Furuyama S, Nugent CA. Circadian rhythm of plasma aldosterone concentration in patients with primary aldosteronism. J Clin Invest 1973; 52: 2272-2277
    CrossrefPubMedGoogle Scholar
  • 106 Sonoyama T, Sone M, Tamura N, Honda K, Taura D, Kojima K, Fukuda Y, Kanamoto N, Miura M, Yasoda A, Arai H, Itoh H, Nakao K. Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism. Endocr Connect 2014; 3: 173-179
    CrossrefPubMedGoogle Scholar
  • 107 Lichtenauer U, Gerum S, Asbach E, Manolopoulou J, Fourkiotis V, Quinkler M, Bidlingmaier M, Reincke M. The clinical value of salivary aldosterone in diagnosis and follow–up of Primary aldosteronism. Horm Metab Res 2016; 48: 638-643
    Article in Thieme ConnectPubMedGoogle Scholar
  • 108 Nakamura Y, Satoh F, Morimoto R, Kudo M, Takase K, Gomez-Sanchez CE. 18-Oxocortisol measurement in adrenal vein sampling as a biomarker for subclassifying primary aldosteronism. J Clin Endocrinol Metab 2011; 96: E1272-E1278
    CrossrefPubMedGoogle Scholar
  • 109 Hennings J, Sundin A, Hägg 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: 963-967
    CrossrefPubMedGoogle Scholar
  • 110 Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, Azizan EA, Aigbirhio F, Gurnell M, Brown MJ. 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: 100-109
    CrossrefPubMedGoogle Scholar
  • 111 Pechère-Bertschi A, Herpin D, Lefebvre H. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism. Ann Endocrinol 2016; 77: 226-234
    CrossrefPubMedGoogle Scholar
  • 112 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: 1000-1006
    Article in Thieme ConnectPubMedGoogle Scholar
  • 113 Steichen O, Zinzindohoué F, Plouin P-F, Amar L. Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: a review. Horm Metab Res 2012; 44: 221-227
    Article in Thieme ConnectPubMedGoogle Scholar
  • 114 Oelkers W, Diederich S, Bähr V. Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage. J Clin Endocrinol Metab 2000; 85: 3266-3270
    CrossrefPubMedGoogle Scholar
  • 115 Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol 2007; 66: 607-618
    CrossrefPubMedGoogle Scholar
  • 116 Tsiavos V, Markou A, Papanastasiou L, Kounadi T, Androulakis II, Voulgaris N, Zachaki A, Kassi E, Kaltsas G, Chrousos GP, Piaditis GP. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol 2016; 175: 21-28
    CrossrefPubMedGoogle Scholar
  • 117 Wu VC, Chang HW, Liu KL, Lin YH, Chueh SC, Lin WC, Ho YL, Huang JW, Chiang CK, Yang SY, Chen YM, Wang SM, Huang KH, Hsieh BS, Wu KD. TAIPAI Study Group Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests. Am J Hypertens 2009; 22: 821-827
    CrossrefPubMedGoogle Scholar
  • 118 Asbach E, Bekeran M, Reincke M. Parathyroid gland function in primary aldosteronism. Horm Metab Res 2015; 47: 994-999
    Article in Thieme ConnectPubMedGoogle Scholar
  • 119 Ferriss JB, Brown JJ, Cumming AM, Fraser R, Lever AF, Peacock M, Robertson JI. Primary hyperparathyroidism associated with primary hyperaldosteronism. Acta Endocrinol 1983; 103: 365-370
    PubMedGoogle Scholar
  • 120 Herd GW. A case of primary hyperparathyroidism, primary hyperaldosteronism and Cushing’s disease. Acta Endocrinol 1984; 107: 371-374
    PubMedGoogle Scholar
  • 121 Maniero C, Fassina A, Guzzardo V, Lenzini L, Amadori G, Pelizzo MR, Gomez-Sanchez C, Rossi GP. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension 2011; 58: 341-346
    CrossrefPubMedGoogle Scholar
  • 122 Concistré A, Petramala L, Zinnamosca L, Settevendemmie A, Corpaci F, Marinelli C, Tonnarini GF, D’Ermo G, De Toma G, Letizia C. Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre. Eur Rev Med Pharmacol Sci 2015; 19: 971-976
    PubMedGoogle Scholar
  • 123 Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 1966; 95: 1109-1119
    PubMedGoogle Scholar
  • 124 New MI, Peterson RE. A new form of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1967; 27: 300-305
    CrossrefPubMedGoogle Scholar
  • 125 Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355: 262-265
    CrossrefPubMedGoogle Scholar
  • 126 Stowasser M, Gordon RD, Tunny TJ, Klemm SA, Finn WL, Krek AL. Familial hyperaldosteronism type II: five families with a new variety of primary aldosteronism. Clin Exp Pharmacol Physiol 1992; 19: 319-322
    CrossrefPubMedGoogle Scholar
  • 127 Lafferty AR, Torpy DJ, Stowasser M, Taymans SE, Lin JP, Huggard P, Gordon RD, Stratakis CA. A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). J Med Genet 2000; 37: 831-835
    CrossrefPubMedGoogle Scholar