Clinical Characteristics and Long-Term Outcome of Primary Aldosteronism in a Norwegian Population

Marianne Aardal Grytaas; Siri S. Strømsøy; Jarle Tor Rørvik; Jarle Birger Arnes; Anette Heie; Thomas Arnesen; Melissa D. Jørstad; Bjørn Gunnar Nedrebø; Dag Erik Jøssang; Dag Kjartan Jensen; Håvard D. Rørvik; Jørn Vegard Sagen; Gunnar Mellgren; Hrafnkell B. Thordarson; Eystein Sverre Husebye; Kristian Løvås

doi:10.1055/s-0043-118909

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2017; 49(11): 838-846
DOI: 10.1055/s-0043-118909

Endocrine Care

Clinical Characteristics and Long-Term Outcome of Primary Aldosteronism in a Norwegian Population

Marianne Aardal Grytaas

¹Department of Clinical Science, University of Bergen, Bergen, Norway

²Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway

,

Siri S. Strømsøy

³Department of Molecular Biology, University of Bergen, Bergen, Norway

,

Jarle Tor Rørvik

⁴Department of Clinical Medicine, University of Bergen, Bergen, Norway

⁵Department of Radiology, Haukeland University Hospital, Bergen, Norway

,

Jarle Birger Arnes

⁶Department of Pathology, Haukeland University Hospital, Bergen, Norway

,

Anette Heie

⁷Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway

,

Thomas Arnesen

³Department of Molecular Biology, University of Bergen, Bergen, Norway

⁷Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway

,

Melissa D. Jørstad

⁸The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway

,

Bjørn Gunnar Nedrebø

¹Department of Clinical Science, University of Bergen, Bergen, Norway

⁹Department of Internal Medicine, Haugesund Hospital, Haugesund, Norway

,

Dag Erik Jøssang

⁵Department of Radiology, Haukeland University Hospital, Bergen, Norway

,

Dag Kjartan Jensen

⁵Department of Radiology, Haukeland University Hospital, Bergen, Norway

,

Håvard D. Rørvik

⁴Department of Clinical Medicine, University of Bergen, Bergen, Norway

,

Jørn Vegard Sagen

¹Department of Clinical Science, University of Bergen, Bergen, Norway

⁸The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway

,

Gunnar Mellgren

¹Department of Clinical Science, University of Bergen, Bergen, Norway

⁸The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway

,

Hrafnkell B. Thordarson

¹Department of Clinical Science, University of Bergen, Bergen, Norway

²Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway

,

Eystein Sverre Husebye

¹Department of Clinical Science, University of Bergen, Bergen, Norway

²Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway

,

Kristian Løvås

¹Department of Clinical Science, University of Bergen, Bergen, Norway

²Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway

› Author Affiliations

Abstract

Primary aldosteronism (PA) is the most common cause of secondary hypertension (HT). We describe here clinical characteristics, diagnostic procedures, and long-term outcomes in a Norwegian population. All suspected PA patients investigated at a tertiary centre from 1998–2012 were retrospectively evaluated. Inclusion criteria were verified PA after confirmatory testing or otherwise considered highly likely PA. Clinical, biochemical, radiological, and adrenal vein sampling (AVS) findings were analysed. Surgically removed adrenals were re-evaluated histopathologically and tested for somatic mutations. All patients still alive by August 2014 were invited to a follow-up visit. One-hundred and eight patients were included, of whom 85% had a history of hypokalaemia. PA was verified by confirmatory testing in 83 (77%), and AVS performed in 95 (88%) patients. The proportion with AVS-confirmed bilateral PA increased during the study period. Sixty-eight patients (63%) underwent adrenalectomy. KCNJ5 mutations were found in 30% of the surgical specimens and were associated with female sex and a florid PA phenotype. Follow-up visits were undertaken in 73/108 (68%), of whom 52 adrenalectomised. After adrenalectomy, 83% were biochemically cured of PA, but only 21% were cured for HT. Female sex, a verified adenoma, and KCNJ5 mutations were associated with cure of HT. In conclusion, the majority of our patients had unilateral PA and hypokalaemia, indicating that patients with bilateral and milder PA may still be underdiagnosed. Female sex, a histopathological adenoma, and the presence of KCNJ5 mutations predicted cure of HT after adrenalectomy, but the overall cure rate of HT was low.

Key words

primary aldosteronism - KCNJ5 - adrenal venous sampling - adrenalectomy

Full Text

References

References
1 Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F. Investigators PS. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am College Cardiol 2006; 48: 2293-2300
2 Nishizaka MK, Pratt-Ubunama M, Zaman MA, Cofield S, Calhoun DA. Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension. Am J Hyperten 2005; 18: 805-812
3 Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient’s cohorts and in population-based studies–a review of the current literature. Horm Metab Res 2012; 44: 157-162
4 Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mannelli M, Matterello MJ, Montemurro D, Palumbo G, Rizzoni D, Rossi E, Pessina AC, Mantero F. Participants PS. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension 2006; 48: 232-238
5 Born-Frontsberg E, Reincke M, Rump LC, Hahner S, Diederich S, Lorenz R, Allolio B, Seufert J, Schirpenbach C, Beuschlein F, Bidlingmaier M, Endres S, Quinkler M. Participants of the German Conn’s R. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: Results of the German Conn’s Registry. J Clin Endocrinol Metab 2009; 94: 1125-1130
6 Savard S, Amar L, Plouin PF, Steichen O. Cardiovascular complications associated with primary aldosteronism: A controlled cross-sectional study. Hypertension 2013; 62: 331-336
7 Reincke M, Fischer E, Gerum S, Merkle K, Schulz S, Pallauf A, Quinkler M, Hanslik G, Lang K, Hahner S, Allolio B, Meisinger C, Holle R, Beuschlein F, Bidlingmaier M, Endres S. German Conn’s Registry-Else Kroner-Fresenius-Hyperaldosteronism R. Observational study mortality in treated primary aldosteronism: the German Conn’s registry. Hypertension 2012; 60: 618-624
8 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr. WF, Montori VM, Endocrine S. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281
9 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
10 Lim V, Guo Q, Grant CS, Thompson GB, Richards ML, Farley DR, Young Jr. WF. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712-2719
11 Young WF, Stanson AW, Thompson GB, Grant CS, Farley DR, van Heerden JA. Role for adrenal venous sampling in primary aldosteronism. Surgery 2004; 136: 1227-1235
12 Sechi LA, Novello M, Lapenna R, Baroselli S, Nadalini E, Colussi GL, Catena C. Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295: 2638-2645
13 Rossi GP, Cesari M, Cuspidi C, Maiolino G, Cicala MV, Bisogni V, Mantero F, Pessina AC. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension 2013; 62: 62-69
14 Wu VC, Wang SM, Chang CH, Hu YH, Lin LY, Lin YH, Chueh SC, Chen L, Wu KD. Long term outcome of Aldosteronism after target treatments. Sci Rep 2016; 6: 32103
15 Choi M, Scholl UI, Yue P, Bjorklund 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, Akerstrom G, Wang W, Carling T, Lifton RP. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 2011; 331: 768-772
16 Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen HN, Lichtenauer UD, Penton D, Schack VR, Amar L, Fischer E, Walther A, Tauber P, Schwarzmayr T, Diener S, Graf E, Allolio B, Samson-Couterie B, Benecke A, Quinkler M, Fallo F, Plouin PF, Mantero F, Meitinger T, Mulatero P, Jeunemaitre X, Warth R, Vilsen B, Zennaro MC, Strom TM, Reincke M. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet 2013; 45: 440-444 444e1–2
17 Scholl UI, Goh G, Stolting 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, Akerstrom G, Bjorklund 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
18 Tadjine M, Lampron A, Ouadi L, Bourdeau I. Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin Endocrinol 2008; 68: 264-270
19 Scholl UI, Healy JM, Thiel A, Fonseca AL, Brown TC, Kunstman JW, Horne MJ, Dietrich D, Riemer J, Kucukkoylu 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
20 Fernandes-Rosa FL, Williams TA, Riester A, Steichen O, Beuschlein F, Boulkroun S, Strom TM, Monticone S, Amar L, Meatchi T, Mantero F, Cicala MV, Quinkler M, Fallo F, Allolio B, Bernini G, Maccario M, Giacchetti G, Jeunemaitre X, Mulatero P, Reincke M, Zennaro MC. Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma. Hypertension 2014; 64: 354-361
21 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, Kusters B. Adrenal nodularity and somatic mutations in primary aldosteronism: One node is the culprit?. J Clin Endocrinol Metab 2014; 99: E1341-E1351
22 Akerstrom T, Willenberg HS, Cupisti K, Ip J, Backman S, Moser A, Maharjan R, Robinson B, Iwen KA, Dralle H. CDV Backdahl M, Botling J, Stalberg P, Westin G, Walz MK, Lehnert H, Sidhu S, Zedenius J, Bjorklund P, Hellman P. Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas. Endocr Relat Cancer 2015; 22: 735-744
23 Steichen O, Zinzindohoue F, Plouin PF, Amar L. Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: A review. Horm Metab Res 2012; 44: 221-227
24 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: 717-723
25 Vincent JM, Morrison ID, Armstrong P, Reznek RH. The size of normal adrenal glands on computed tomography. Clin Radiol 1994; 49: 453-455
26 Young Jr. WF, Stanson AW, Grant CS, Thompson GB, van Heerden JA. Primary aldosteronism: adrenal venous sampling. Surgery 1996; 120: 913-919 discussion 919–920
27 Viste K, Grytaas MA, Jorstad MD, Jossang DE, Hoyden EN, Fotland SS, Jensen DK, Lovas K, Thordarson H, Almas B, Mellgren G. Efficacy of adrenal venous sampling is increased by point of care cortisol analysis. Endocr Connect 2013; 2: 236-242
28 Arnesen T, Glomnes N, Stromsoy S, Knappskog S, Heie A, Akslen LA, Grytaas M, Varhaug JE, Gimm O, Brauckhoff M. Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: A population-based study from Western Norway. Langenbecks Arch Surgery/Dtsch Ges Chirug 2013; 398: 869-874
29 Vonend O, Ockenfels N, Gao X, Allolio B, Lang K, Mai K, Quack I, Saleh A, Degenhart C, Seufert J, Seiler L, Beuschlein F, Quinkler M, Podrabsky P, Bidlingmaier M, Lorenz R, Reincke M, Rump LC, German Conn’s R. Adrenal venous sampling: evaluation of the German Conn’s registry. Hypertension 2011; 57: 990-995
30 Riester A, Fischer E, Degenhart C, Reiser MF, Bidlingmaier M, Beuschlein F, Reincke M, Quinkler M. Age below 40 or a recently proposed clinical prediction score cannot bypass adrenal venous sampling in primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 1035-1039
31 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
32 El Ghorayeb N, Mazzuco TL, Bourdeau I, Mailhot JP, Zhu PS, Therasse E, Lacroix A. Basal and Post-ACTH Aldosterone and Its Ratios Are Useful During Adrenal Vein Sampling in Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101: 1826-1835
33 Hannemann A, Bidlingmaier M, Friedrich N, Manolopoulou J, Spyroglou A, Volzke H, Beuschlein F, Seissler J, Rettig R, Felix SB, Biffar R, Doring A, Meisinger C, Peters A, Wichmann HE, Nauck M, Wallaschofski H, Reincke M. Screening for primary aldosteronism in hypertensive subjects: results from two German epidemiological studies. Eur J Endocrinol 2012; 167: 7-15
34 Lenzini L, Rossitto G, Maiolino G, Letizia C, Funder JW, Rossi GP. A Meta-Analysis of Somatic KCNJ5 K(+) Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma. J Clin Endocrinol Metab 2015; 100: E1089-E1095
35 Weigel M, Riester A, Hanslik G, Lang K, Willenberg HS, Endres S, Allolio B, Beuschlein F, Reincke M, Quinkler M. Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism. Eur J Endocrinol 2015; 172: 443-450
36 Volpe C, Hamberger B, Hoog A, Mukai K, Calissendorff J, Wahrenberg H, Zedenius J, Thoren M. Primary aldosteronism: Functional histopathology and long-term follow-up after unilateral adrenalectomy. Clin Endocrinol 2015; 82: 639-647
37 Letavernier E, Peyrard S, Amar L, Zinzindohoue F, Fiquet B, Plouin PF. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J Hyperten 2008; 26: 1816-1823
38 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: 1477-1484
39 Rossi GP, Bolognesi M, Rizzoni D, Seccia TM, Piva A, Porteri E, Tiberio GA, Giulini SM, Agabiti-Rosei E, Pessina AC. Vascular remodeling and duration of hypertension predict outcome of adrenalectomy in primary aldosteronism patients. Hypertension 2008; 51: 1366-1371
40 Citton M, Viel G, Rossi GP, Mantero F, Nitti D, Iacobone M. Outcome of surgical treatment of primary aldosteronism. Langenbecks Arch Surgery/Dtsch Ges Chirurg 2015; 400: 325-331

Supplementary Material

Supplementary Material