Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas

in European Journal of Endocrinology
View More View Less
  • 1 Department of Endocrinology and Diabetes Center, ‘G. Gennimatas’, General Hospital of Athens, Athens, Greece
  • | 2 Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • | 3 Department of Endocrinology, Athens Naval and Veterans Hospital, Athens, Greece
  • | 4 Third Department of Surgery, Athens General Hospital ‘G. Gennimatas’, Athens, Greece
  • | 5 George P. Chrousos, University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
  • | 6 Department of Endocrinology, Diabetes and Metabolic Diseases, Henry Dunant Hospital Center, Athens, Greece

Correspondence should be addressed to A Markou; Email: amarkouuk@yahoo.co.uk
Restricted access

Objective

Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6 to 16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone saline infusion test (DSIT) by applying both tests on the same subjects.

Methods

We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls with normal adrenal imaging. Serum cortisol, aldosterone, and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean ± 2 s.d. values from the controls, we defined the upper normal limits for cortisol, aldosterone, and PRC for both the SIT and DSIT.

Results

In the controls, the post-DSIT aldosterone levels and the ARR were approximately two-fold and three-fold lower, respectively, than the corresponding post-SIT values (all P  = 0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion (ACS). Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics.

Conclusions

The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk of developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant ACS.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 1705 1705 131
Full Text Views 122 122 14
PDF Downloads 192 192 16
  • 1

    Schirpenbach C, Reincke M. Screening for primary aldosteronism. Best Practice and Research: Clinical Endocrinology and Metabolism 2006 20 369384. (https://doi.org/10.1016/j.beem.2006.07.007)

    • Search Google Scholar
    • Export Citation
  • 2

    Kaplan NM The current epidemic of primary aldosteronism: causes and consequences. Journal of Hypertension 2004 22 863869. (https://doi.org/10.1097/00004872-200405000-00001)

    • Search Google Scholar
    • Export Citation
  • 3

    Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, Kestenbaum B, de Boer IH, Vaidya A. The spectrum of subclinical primary aldosteronism and incident hypertension: a cohort study. Annals of Internal Medicine 2017 167 630641. (https://doi.org/10.7326/M17-0882)

    • Search Google Scholar
    • Export Citation
  • 4

    Vaidya A, Mulatero P, Baudrand R, Adler GK, Xavier SF. The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment. Endocrine Review 2018 39 10571088. (https://doi.org/10.1210/er.2018-00139/5074252)

    • Search Google Scholar
    • Export Citation
  • 5

    Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, Papadopoulos N, Vogiatzis K, Zamboulis C. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008 371 19211926. (available at: www.thelancet.com)(https://doi.org/10.1016/S0140-6736(08)60834-X)

    • Search Google Scholar
    • Export Citation
  • 6

    Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mannelli M & Matterello MJ et al.Renal damage in primary aldosteronism: results of the PAPY study. Hypertension 2006 48 232238. (https://doi.org/10.1161/01.HYP.0000230444.01215.6a)

    • Search Google Scholar
    • Export Citation
  • 7

    Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, Vaidya A. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Annals of Internal Medicine 2020 173 1020. (https://doi.org/10.7326/M20-0065)

    • Search Google Scholar
    • Export Citation
  • 8

    Piaditis GP, Kaltsas GA, Androulakis II, Gouli A, Makras P, Papadogias D, Dimitriou K, Ragkou D, Markou A & Vamvakidis K et al.High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clinical Endocrinology 2009 71 772778. (https://doi.org/10.1111/j.1365-2265.2009.03551.x)

    • Search Google Scholar
    • Export Citation
  • 9

    Gouli A, Kaltsas G, Tzonou A, Markou A, Androulakis II, Ragkou D, Vamvakidis K, Zografos G, Kontogeorgos G & Chrousos GP et al.High prevalence of autonomous aldosterone secretion among patients with essential hypertension. European Journal of Clinical Investigation 2011 41 12271236. (https://doi.org/10.1111/j.1365-2362.2011.02531.x)

    • Search Google Scholar
    • Export Citation
  • 10

    Papanastasiou L, Markou A, Pappa T, Gouli A, Tsounas P, Fountoulakis S, Kounadi T, Tsiama V, Dasou A & Gryparis A et al.Primary aldosteronism in hypertensive patients: clinical implications and target therapy. European Journal of Clinical Investigation 2014 44 697706. (https://doi.org/10.1111/eci.12286)

    • Search Google Scholar
    • Export Citation
  • 11

    Tsiavos V, Markou A, Papanastasiou L, Kounadi T, Androulakis II, Voulgaris N, Zachaki A, Kassi E, Kaltsas G & Chrousos GP et al.A new highly sensitive and specific overnight combined screening and 1 diagnostic test for primary aldosteronism. European Journal of Endocrinology 2016 175 2128. (https://doi.org/10.1530/EJE-16-0003)

    • Search Google Scholar
    • Export Citation
  • 12

    Pappa T, Papanastasiou L, Kaltsas G, Markou A, Tsounas P, Androulakis I, Tsiavos V, Zografos G, Vamvakidis K & Samara C et al.Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension. Journal of Clinical Endocrinology and Metabolism 2012 97 E537E545. (https://doi.org/10.1210/jc.2011-2874)

    • Search Google Scholar
    • Export Citation
  • 13

    Bernini G, Moretti A, Argenio G, Salvetti A. Primary aldosteronism in normokalemic patients with adrenal incidentalomas. European Journal of Endocrinology 2002 146 523529. (https://doi.org/10.1530/eje.0.1460523)

    • Search Google Scholar
    • Export Citation
  • 14

    Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocrine Reviews 2004 25 309340. (https://doi.org/10.1210/er.2002-0031)

    • Search Google Scholar
    • Export Citation
  • 15

    Stavropoulos K, Imprialos KP, Katsiki N, Petidis K, Kamparoudis A, Petras P, Georgopoulou V, Finitsis S, Papadopoulos C & Athyros VG et al.Primary aldosteronism in patients with adrenal incidentaloma: is screening appropriate for everyone? Journal of Clinical Hypertension 2018 20 942948. (https://doi.org/10.1111/jch.13291)

    • Search Google Scholar
    • Export Citation
  • 16

    Markou A, Pappa T, Kaltsas G, Gouli A, Mitsakis K, Tsounas P, Prevoli A, Tsiavos V, Papanastasiou L & Zografos G et al.Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension. Journal of Clinical Endocrinology and Metabolism 2013 98 14091416. (https://doi.org/10.1210/jc.2012-3353)

    • Search Google Scholar
    • Export Citation
  • 17

    Piaditis G, Markou A, Papanastasiou L, Androulakis II, Kaltsas G. Progress in aldosteronism: a review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. European Journal of Endocrinology 2015 172 R191R203. (https://doi.org/10.1530/EJE-14-0537)

    • Search Google Scholar
    • Export Citation
  • 18

    Ghorayeb el N, Bourdeau I, Lacroix A. Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism. Frontiers in Endocrinology 2016 7 72. (https://doi.org/10.3389/fendo.2016.00072)

    • Search Google Scholar
    • Export Citation
  • 19

    Hattangady NG, Olala LO, Bollag WB, Rainey WE. Acute and chronic regulation of aldosterone production. Molecular and Cellular Endocrinology 2012 350 151162. (https://doi.org/10.1016/j.mce.2011.07.034)

    • Search Google Scholar
    • Export Citation
  • 20

    Seely EW, Conlin PR, Brent GA, Dluhy RG. Adrenocorticotropin stimulation of aldosterone: prolonged continuous versus pulsatile infusion. Journal of Clinical Endocrinology and Metabolism 1989 69 10281032. (https://doi.org/10.1210/jcem-69-5-1028)

    • Search Google Scholar
    • Export Citation
  • 21

    Arvat E Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: dose-response study. Journal of Clinical Endocrinology and Metabolism 2000 85 31413146. (https://doi.org/10.1210/jcem.85.9.6784)

    • Search Google Scholar
    • Export Citation
  • 22

    Markou A, Sertedaki A, Kaltsas G, Androulakis II, Marakaki C, Pappa T, Gouli A, Papanastasiou L, Fountoulakis S & Zacharoulis A et al.Stress-induced aldosterone hyper-secretion in a substantial subset of patients with essential hypertension. Journal of Clinical Endocrinology and Metabolism 2015 100 28572864. (https://doi.org/10.1210/jc.2015-1268)

    • Search Google Scholar
    • Export Citation
  • 23

    Luger A, Deuster PA, Kyle SB, Gallucci WT, Montgomery LC, Gold PW, Loriaux DL, Chrousos GP. Acute hypothalamic–pituitary–adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training. New England Journal of Medicine 1987 316 13091315. (https://doi.org/10.1056/NEJM198705213162105)

    • Search Google Scholar
    • Export Citation
  • 24

    Luger A, Deuster PA, Debolt JE, Loriaux DL, Chrousos GP. Acute exercise stimulates the renin-angiotensin-aldosterone axis: adaptive changes in runners. Hormone Research 1988 30 59. (https://doi.org/10.1159/000181017)

    • Search Google Scholar
    • Export Citation
  • 25

    Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2016 101 18891916. (https://doi.org/10.1210/jc.2015-4061)

    • Search Google Scholar
    • Export Citation
  • 26

    Piaditis GP, Kaltsas G, Markou A, Chrousos GP. Five reasons for the failure to diagnose aldosterone excess in hypertension. Hormone and Metabolic Research 2020 52 827833. (https://doi.org/10.1055/a-1236-4869)

    • Search Google Scholar
    • Export Citation
  • 27

    Trowbridge RL, Rencic JJ, Wijesekera TP, Olson APJ. Avoiding cognitive errors in clinical decision making. Annals of Internal Medicine 2020 173 678679. (https://doi.org/10.7326/L20-1059)

    • Search Google Scholar
    • Export Citation
  • 28

    Rossi GP, Sechi LA, Giacchetti G, Ronconi V, Strazzullo P, Funder JW. Primary aldosteronism: cardiovascular, renal and metabolic implications. Trends in Endocrinology and Metabolism 2008 19 8890. (https://doi.org/10.1016/j.tem.2008.01.006)

    • Search Google Scholar
    • Export Citation
  • 29

    Neves MF, Schiffrin EL. Aldosterone: a risk factor for vascular disease. Current Hypertension Reports 2003 5 5965. (https://doi.org/10.1007/s11906-003-0012-2)

    • Search Google Scholar
    • Export Citation
  • 30

    Gilbert KC, Brown NJ. Aldosterone and inflammation. Current Opinion in Endocrinology, Diabetes, and Obesity 2010 17 199204. (https://doi.org/10.1097/MED.0b013e3283391989)

    • Search Google Scholar
    • Export Citation
  • 31

    Carey RM Aldosterone and cardiovascular disease. Current Opinion in Endocrinology, Diabetes, and Obesity 2010 17 194198. (https://doi.org/10.1097/MED.0b013e3283390fa4)

    • Search Google Scholar
    • Export Citation
  • 32

    Xu Z, Yang J, Hu J, Song Y, He W, Luo T, Cheng Q, Ma L, Luo R & Fuller PJ et al.Primary aldosteronism in patients in China with recently detected hypertension. Journal of the American College of Cardiology 2020 75 19131922. (https://doi.org/10.1016/j.jacc.2020.02.052)

    • Search Google Scholar
    • Export Citation
  • 33

    Farquharson CAJ, Struthers AD. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clinical Science 2002 103 425431. (https://doi.org/10.1042/cs1030425)

    • Search Google Scholar
    • Export Citation
  • 34

    Vaidya A, Underwood PC, Hopkins PN, Jeunemaitre X, Ferri C, Williams GH, Adler GK. Aldosterone and cardiometabolic risk factors abnormal aldosterone physiology and cardiometabolic risk factors. Hypertension 2013 61 886 – 893. (https://doi.org/10.1161/HYPERTENSIONAHA)

    • Search Google Scholar
    • Export Citation
  • 35

    Frustaci A, Letizia C, Verardo R, Grande C, Francone M, Sansone L, Russo MA, Chimenti C. Primary aldosteronism-associated cardiomyopathy: clinical-pathologic impact of aldosterone normalization. International Journal of Cardiology 2019 292 141147. (https://doi.org/10.1016/j.ijcard.2019.06.055)

    • Search Google Scholar
    • Export Citation
  • 36

    Gkaliagkousi E, Anyfanti P, Triantafyllou A, Gavriilaki E, Nikolaidou B, Lazaridis A, Vamvakis A, Douma S. Aldosterone as a mediator of microvascular and macrovascular damage in a population of normotensive to early-stage hypertensive individuals. Journal of the American Society of Hypertension 2018 12 5057. (https://doi.org/10.1016/j.jash.2017.12.001)

    • Search Google Scholar
    • Export Citation
  • 37

    Baudrand R, Guarda FJ, Fardella C, Hundemer G, Brown J, Williams G, Vaidya A. Continuum of renin-independent aldosteronism in normotension. Hypertension 2017 69 950956. (https://doi.org/10.1161/HYPERTENSIONAHA.116.08952)

    • Search Google Scholar
    • Export Citation
  • 38

    Brooks RV, Felix-Davies D, Lee MR, Robertson PW. Hyperaldosteronism from adrenal carcinoma. BMJ 1972 1 220221. (https://doi.org/10.1136/bmj.1.5794.220)

    • Search Google Scholar
    • Export Citation
  • 39

    Lin X, Miao X, Zhu P, Lin F. A normotensive patient with primary aldosteronism. Case Reports in Endocrinology 2017 2017 5159382. (https://doi.org/10.1155/2017/5159382)

    • Search Google Scholar
    • Export Citation
  • 40

    Médeau V, Moreau F, Trinquart L, Clemessy M, Wémeau JL, Vantyghem MC, Plouin PF, Reznik Y. Clinical and biochemical characteristics of normotensive patients with primary aldosteronism: a comparison with hypertensive cases. Clinical Endocrinology 2008 69 2028. (https://doi.org/10.1111/j.1365-2265.2008.03213.x)

    • Search Google Scholar
    • Export Citation
  • 41

    Barzon L, Sonino N, Fallo F, Palù G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. European Journal of Endocrinology 2003 149 273285. (https://doi.org/10.1530/eje.0.1490273)

    • Search Google Scholar
    • Export Citation
  • 42

    Kjellbom A, Lindgren O, Puvaneswaralingam S, Löndahl M, Olsen H. Association between mortality and levels of autonomous cortisol secretion by adrenal incidentalomas: a cohort study. Annals of Internal Medicine 2021 174 10411049. (https://doi.org/10.7326/M20-7946)

    • Search Google Scholar
    • Export Citation