Abstract
Primary aldosteronism (PA) is the most common endocrine cause of resistant hypertension. Individuals with PA are at increased cardiovascular risk, and an appropriate management and treatment would ideally reduce such risk. Screening and diagnosis of PA requires a specific diagnostic test which is considered time- and cost-consuming and, as a result, is underperformed in clinical practice. An online survey reviewing available diagnostic procedures, laboratory testing, and clinical protocols for screening and confirmation of PA diagnosis was conducted among clinical lead of Reference and Excellence centers of the Italian Hypertension Society. A total of 102 questionnaires were sent and 62 centers participated in the survey. Assessment of the plasma renin (plasma renin activity/direct renin concentration) and plasma aldosterone concentration (PAC) was available in all centers. Captopril challenge test (CCT) and saline infusion test (SIT) were available in 60% and 61% of the centers, respectively. Fludrocortisone suppression test was available in 32% of the units. Adrenal vein sampling was accessible in 32% of the centers. We found discrepancies in cutoff levels of aldosterone-to-renin ratio (ARR) and PAC after SIT. Other discrepancies involved the duration of the wash-out period before ARR testing and dosage of captopril administered during CCT. In conclusion, although all centers are sufficiently equipped to perform PA screening, often patients should be referred to other centers to confirm the diagnosis of PA. A greater uniformity across centers to define precise cutoffs for screening and confirmatory testing for the diagnosis of PA would be of utility.
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Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016;388:2665–712.
Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317:165–82.
Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:1403–19.
Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, et al. J Am Coll Cardiol. 2006;48:2293–300.
Lim PO, Dow E, Brennan G, Jung RT, MacDonald TM. High prevalence of primary aldosteronism in the Tayside hypertension clinic population. J Hum Hypertens. 2000;14:311–5.
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.
Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002;40:892–6.
Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, et al. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension. 2006;48:232–8.
Monticone S, D’Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6:41–50.
Lin YH, Lin LY, Chen A, et al. Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma. Atherosclerosis. 2012;221:154–9.
Rossi GP, Sacchetto A, Visentin P, Canali C, Graniero GR, Palatini P, et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension. 1996;27:1039–45.
Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension. 2007;50:911–8.
Ohno Y, Sone M, Inagaki N, Yamasaki T, Ogawa O, Takeda Y, et al. Prevalence of cardiovascular disease and its risk factors in primary aldosteronism: a multicenter study in Japan. Hypertension. 2018;71:530–7.
Savard S, Amar L, Plouin PF, Steichen O. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension. 2013;62:331–6.
Mulatero P, Monticone S, Bertello C, Viola A, Tizzani D, Iannaccone A, et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab. 2013;98:4826–33.
Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45:1243–8.
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.
Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. Case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:1889–916.
Mulatero P, Monticone S, Burrello J, Veglio F, Williams TA, Funder J. Guidelines for primary aldosteronism: uptake by primary care physicians in Europe. J Hypertens. 2016;34:2253–7.
Tocci G, De Luca N, Sarzani R, Ambrosioni E, Borghi C, Cottone S, et al. National survey on excellence centers and reference centers for hypertension diagnosis and treatment: geographical distribution, medical facilities and diagnostic opportunities. High Blood Press Cardiovasc Prev. 2014;21:29–36.
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;6:51–59.
Velema MS, Terlouw JM, de Nooijer AH, Nijkamp MD, Jacobs N, Deinum J. Psychological symptoms and well-being after treatment for primary aldosteronism. Horm Metab Res. 2018. https://doi.org/10.1055/a-0628-6847.
Ahmed AH, Gordon RD, Sukor N, Pimenta E, Stowasser M. Quality of life in patients with bilateral primary aldosteronism before and during treatment with spironolactone and/or amiloride, including a comparison with our previously published results in those with unilateral disease treated surgically. J Clin Endocrinol Metab. 2011;96:2904–11.
Burrello J, Monticone S, Buffolo F, Lucchiari M, Tetti M, Rabbia F, et al. Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in primary aldosteronism. J Hypertens. 2016;34:920–7.
Dorrian CA, Toole BJ, Alvarez-Madrazo S, Kelly A, Connell JM, Wallace AM. A screening procedure for primary aldosteronism based on the Diasorin Liaison automated chemiluminescent immunoassay for direct renin. Ann Clin Biochem. 2010;47:195–9.
Rossi GP, Ceolotto G, Rossitto G, Seccia TM, Maiolino G, Berton C, et al. Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension. Clin Chem Lab Med. 2016;54:1441–50.
Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R, et al. Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. J Hypertens. 2015;33:2500–11.
Fischer E, Beuschlein F, Bidlingmaier M, Reincke M. Commentary on the Endocrine Society Practice Guidelines: consequences of adjustment of antihypertensive medication in screening of primary aldosteronism. Rev Endocr Metab Disord. 2011;12:43–48.
Stowasser M, Gordon RD. Primary aldosteronism—careful investigation is essential and rewarding. Mol Cell Endocrinol. 2004;217:33–39.
Song Y, Yang S, He W, Hu J, Cheng Q, Wang Y, et al. Confirmatory Tests for the Diagnosis of Primary Aldosteronism: A Prospective Diagnostic Accuracy Study. Hypertension. 2018;71:118–24.
Jankowski A, Skorek A, Krzyśko K, Zarzycki PK, Ochocka RJ, Lamparczyk H. Captopril: determination in blood and pharmacokinetics after single oral dose. J Pharm Biomed Anal. 1995;13:655–60.
Cornu E, Steichen O, Nogueira-Silva L, Küpers E, Pagny JY, Grataloup C, et al. Suppression of aldosterone secretion after recumbent saline infusion does not exclude lateralized primary aldosteronism. Hypertension. 2016;68:989–94.
Monticone S, Viola A, Rossato D, Veglio F, Reincke M, Gomez-Sanchez C, et al. Adrenal vein sampling in primary aldosteronism: towards a standardised protocol. Lancet Diabetes Endocrinol. 2015;3:296–303.
Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, et al. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009;151:329–37.
Dekkers T, Prejbisz A, Kool LJS, Groenewoud HJMM, 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.
Beuschlein F, Mulatero P, Asbach E, Monticone S, Catena C, Sechi LA, et al. The SPARTACUS trial: controversies and unresolved issues. Horm Metab Res. 2017;49:936–42.
Buffolo F, Monticone S, Williams TA, Rossato D, Burrello J, Tetti M, et al. Subtype diagnosis of primary aldosteronism: is adrenal vein sampling always necessary? Int J Mol Sci. 2017;18:pii: E848.
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.
Monticone S, Satoh F, Dietz AS, Goupil R, Lang K, Pizzolo F, et al. Clinical management and outcomes of adrenal hemorrhage following adrenal vein sampling in primary aldosteronism. Hypertension. 2016;67:146–52.
Mulatero P, Tizzani D, Viola A, et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension. 2011;58:797–803.
So A, Duffy DL, Gordon RD, et al. Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity. J Hypertens. 2005;23:1477–84.
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Pucci, G., Monticone, S., Agabiti Rosei, C. et al. Diagnosis of primary aldosteronism in the hypertension specialist centers in Italy: a national survey. J Hum Hypertens 32, 745–751 (2018). https://doi.org/10.1038/s41371-018-0094-6
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DOI: https://doi.org/10.1038/s41371-018-0094-6
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