Skip to main content

Advertisement

SpringerLink
Log in

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications.

Methods

Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated.

Results

265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828–0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases.

Conclusions

ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. P. Mulatero, S. Monticone, J. Deinum, L. Amar, A. Prejbisz, M.-C. Zennaro, F. Beuschlein, G.P. Rossi, T. Nishikawa, A. Morganti, T.M. Seccia, Y.-H. Lin, F. Fallo, J. Widimsky, Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J. Hypertens. 38, 1919–28 (2020)

    Article  CAS  PubMed  Google Scholar 

  2. S.C. Käyser, T. Dekkers, H.J. Groenewoud, G.J. van der Wilt, J. Carel Bakx, M.C. van der Wel, A.R. Hermus, J.W. Lenders, J. Deinum, Study heterogeneity and estimation of prevalence of primary aldosteronism: A systematic review and meta-regression analysis. J. Clin. Endocrinol. Metab. 101, 2826–35 (2016)

    Article  PubMed  Google Scholar 

  3. J.M. Brown, M. Siddiqui, D.A. Calhoun, R.M. Carey, P.N. Hopkins, G.H. Williams, A. Vaidya, The unrecognized prevalence of primary aldosteronism: A cross-sectional study. Ann. Intern. Med. 173, 10–20 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  4. W. Kawarazaki, T. Fujita, The role of aldosterone in obesity-related hypertension. Am. J. Hypertens. 29, 415–23 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. V.M. Gershuni, D.S. Herman, R.R. Kelz, R.E. Roses, D.L. Cohen, S.O. Trerotola, D.L. Fraker, H. Wachtel, Challenges in obesity and primary aldosteronism: Diagnosis and treatment. Surgery 167, 204–10 (2020)

    Article  PubMed  Google Scholar 

  6. Y. Ohno, M. Sone, N. Inagaki, T. Yamasaki, O. Ogawa, Y. Takeda, I. Kurihara, H. Umakoshi, T. Ichijo, T. Katabami, N. Wada, Y. Ogawa, T. Yoshimoto, J. Kawashima, M. Watanabe, Y. Matsuda, H. Kobayashi, H. Shibata, S. Miyauchi, K. Kamemura, T. Fukuoka, K. Yamamoto, M. Otsuki, T. Suzuki, M. Naruse, Obesity as a key factor underlying idiopathic hyperaldosteronism. J. Clin. Endocrinol. Metab. 103, 4456–64 (2018)

    Article  PubMed  Google Scholar 

  7. J.G. Ruiz-Sánchez, M. Paja-Fano, M. González Boillos, B. Pla Peris, E. Pascual-Corrales, A.M. García Cano, P. Parra Ramírez, P. Martín Rojas-Marcos, A. Vicente Delgado, E. Gómez Hoyos, R. Ferreira, I. García Sanz, M. Recasens Sala, R. Barahona San Millan, M.J. Picón César, P. Díaz Guardiola, J.J. García González, C.M. Perdomo, L. Manjón Miguélez, R. García Centeno, J.C. Percovich, Á. Rebollo Román, P. Gracia Gimeno, C. Robles Lázaro, M. Morales-Ruiz, F.A. Hanzu, M. Araujo-Castro, Effect of obesity on clinical characteristics of primary aldosteronism patients at diagnosis and postsurgical response. J. Clin. Endocrinol. Metab. 109, e379–e388 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  8. M.N. Pratt-Ubunama, M.K. Nishizaka, R.L. Boedefeld, S.S. Cofield, S.M. Harding, D.A. Calhoun, Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 131, 453–9 (2007)

    Article  CAS  PubMed  Google Scholar 

  9. A. Di Murro, L. Petramala, D. Cotesta, L. Zinnamosca, E. Crescenzi, C. Marinelli, M. Saponara, C. Letizia, Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism. J. Renin-Angiotensin-Aldosterone Syst. 11, 165–72 (2010)

    Article  PubMed  Google Scholar 

  10. A. Pecori, F. Buffolo, J. Pieroni, V. Forestiero, E. Sconfienza, F. Veglio, P. Mulatero, S. Monticone, Primary aldosteronism and obstructive sleep apnea: Casual associationor pathophysiological link. Horm. Metab. Res. 52, 366–72 (2020)

    Article  CAS  PubMed  Google Scholar 

  11. S. Monticone, E. Sconfienza, F. D’Ascenzo, F. Buffolo, F. Satoh, L.A. Sechi, F. Veglio, P. Mulatero, Renal damage in primary aldosteronism: a systematic review and meta-analysis. J. Hypertens. 38, 3–12 (2020)

    Article  CAS  PubMed  Google Scholar 

  12. M. Fernández-Argüeso, E. Pascual-Corrales, N. Bengoa Rojano, A. García Cano, L. Jiménez Mendiguchía, M. Araujo-Castro, Higher risk of chronic kidney disease and progressive kidney function impairment in primary aldosteronism than in essential hypertension. Case-control study. Endocrine 73, 439–46 (2021)

    Article  PubMed  Google Scholar 

  13. Y. Akehi, T. Yanase, R. Motonaga, H. Umakoshi, M. Tsuiki, Y. Takeda, T. Yoneda, I. Kurihara, H. Itoh, T. Katabami, T. Ichijo, N. Wada, Y. Shibayama, T. Yoshimoto, K. Ashida, Y. Ogawa, J. Kawashima, M. Sone, N. Inagaki, K. Takahashi, M. Fujita, M. Watanabe, Y. Matsuda, H. Kobayashi, H. Shibata, K. Kamemura, M. Otsuki, Y. Fujii, K. Yamamoto, A. Ogo, S. Okamura, S. Miyauchi, T. Fukuoka, S. Izawa, S. Hashimoto, M. Yamada, Y. Yoshikawa, T. Kai, T. Suzuki, T. Kawamura, M. Naruse, High prevalence of diabetes in patients with primary aldosteronism (PA) associated with subclinical hypercortisolism and prediabetes more prevalent in bilateral than unilateral PA: A large, multicenter cohort study in Japan. Diabetes Care 42, 938–45 (2019)

    Article  CAS  PubMed  Google Scholar 

  14. G. Hanslik, H. Wallaschofski, A. Dietz, A. Riester, M. Reincke, B. Allolio, K. Lang, I. Quack, L.C. Rump, H.S. Willenberg, F. Beuschlein, M. Quinkler, A. Hannemann, participants of the German Conn’s Registry. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn’s Registry. Eur. J. Endocrinol. 173, 665–75 (2015)

  15. Y. Hu, J. Zhang, W. Liu, X. Su, Determining the Prevalence of Primary Aldosteronism in Patients With New-Onset Type 2 Diabetes and Hypertension. J. Clin. Endocrinol. Metab. 105, dgz293 (2020)

    Article  PubMed  Google Scholar 

  16. S. Monticone, F. D’Ascenzo, C. Moretti, T.A. Williams, F. Veglio, F. Gaita, P. Mulatero, Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 6, 41–50 (2018)

    Article  CAS  PubMed  Google Scholar 

  17. C.-T. Pan, C.-H. Tsai, Z.-W. Chen, Y.-Y. Chang, V.-C. Wu, C.-S. Hung, Y.-H. Lin, Atrial fibrillation in primary aldosteronism. Horm. Metab. Res. 52, 357–65 (2020)

    Article  CAS  PubMed  Google Scholar 

  18. P. Milliez, X. Girerd, P.-F. Plouin, J. Blacher, M.E. Safar, J.-J. Mourad, Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J. Am. Coll. Cardiol. 45, 1243–8 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. Z. Meng, Z. Dai, K. Huang, C. Xu, Y.-G. Zhang, H. Zheng, T.-Z. Liu, Long-term mortality for patients of primary aldosteronism compared with essential hypertension: A systematic review and meta-analysis. Front. Endocrinol. (Lausanne) 11, 121 (2020)

    Article  PubMed  Google Scholar 

  20. P. Mulatero, S. Monticone, C. Bertello, A. Viola, D. Tizzani, A. Iannaccone, V. Crudo, J. Burrello, A. Milan, F. Rabbia, F. Veglio, Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J. Clin. Endocrinol. Metab. 98, 4826–33 (2013)

    Article  CAS  PubMed  Google Scholar 

  21. F. Buffolo, S. Monticone, J. Burrello, M. Tetti, F. Veglio, T. Williams, P. Mulatero, Is primary aldosteronism still largely unrecognized? Horm. Metab. Res. 49, 908–14 (2017)

    Article  CAS  PubMed  Google Scholar 

  22. S.C. Käyser, J. Deinum, W.J. de Grauw, B.W. Schalk, H.J. Bor, J.W. Lenders, T.R. Schermer, M.C. Biermans, Prevalence of primary aldosteronism in primary care: a cross-sectional study. Br. J. Gen. Pract. 68, e114–e122 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  23. J. Funder, Primary aldosteronism: The next five years. Horm. Metab. Res. 49, 977–83 (2017)

    Article  CAS  PubMed  Google Scholar 

  24. L. Handgriff, M. Reincke, [Primary aldosteronism - why is it still underdiagnosed in clinical practice?]. DMW - Dtsch. Medizinische Wochenschr. 145, 716–21 (2020)

    Google Scholar 

  25. Y.Y. Lim, J. Shen, P.J. Fuller, J. Yang, Current pattern of primary aldosteronism diagnosis: Delayed and complicated. Aust. J. Gen. Pract. 47, 712–8 (2018)

    Article  PubMed  Google Scholar 

  26. A.K. Nainani, J. Yang, S. Peters, G. Russell, I can’t understand why others don’t screen more’: A qualitative study exploring why Australian general practitioners screen for primary aldosteronism. BMJ Open 12, e061671 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  27. J.G. Ruiz-Sánchez, M. Pazos Guerra, D. Meneses, I. Runkle, Primary hyperaldosteronism: When to suspect it and how to confirm its diagnosis. Endocrines 3, 29–42 (2022)

    Article  Google Scholar 

  28. J.W. Funder, R.M. Carey, F. Mantero, M.H. Murad, M. Reincke, H. Shibata, M. Stowasser, W.F. Young, The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 101, 1889–916 (2016)

    Article  CAS  PubMed  Google Scholar 

  29. B. Williams, G. Mancia, W. Spiering, E. Agabiti Rosei, M. Azizi, M. Burnier, D. Clement, A. Coca, G. De Simone, A. Dominiczak, T. Kahan, F. Mahfoud, J. Redon, L. Ruilope, A. Zanchetti, M. Kerins, S. Kjeldsen, R. Kreutz, S. Laurent, G.Y.H. Lip, R. McManus, K. Narkiewicz, F. Ruschitzka, R. Schmieder, E. Shlyakhto, K. Tsioufis, V. Aboyans, I. Desormais, 2018 Practice guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Blood Press 27, 314–40 (2018)

    Article  PubMed  Google Scholar 

  30. X. Liu, S. Hao, J. Bian, Y. Lou, H. Zhang, H. Wu, J. Cai, W. Ma, Performance of aldosterone-to-renin ratio before washout of antihypertensive drugs in screening of primary aldosteronism. J Clin Endocrinol Metab. 21, dgae094 (2024). https://doi.org/10.1210/clinem/dgae094

  31. X. Li, J. Liang, J. Hu, L. Ma, J. Yang, A. Zhang, Y. Jing, Y. Song, Y. Yang, Z. Feng, Z. Du, Y. Wang, T. Luo, W. He, X. Shu, S. Yang, Q. Li; Chongqing Primary Aldosteronism Study (CONPASS) Group, Screening for primary aldosteronism on and off interfering medications. Endocrine 83, 178–87 (2024)

    Article  CAS  PubMed  Google Scholar 

  32. G.L. Schwartz, S.T. Turner, Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin. Chem. 51, 386–94 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. P. Jędrusik, B. Symonides, J. Lewandowski, Z. Gaciong, The effect of antihypertensive medications on testing for primary aldosteronism. Front. Pharmacol. 12, 684111 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  34. V.M. Montori, G.L. Schwartz, A.B. Chapman, E. Boerwinkle, S.T. Turner, Validity of the aldosterone-renin ratio used to screen for primary aldosteronism. Mayo Clin. Proc. 76, 877–82 (2001)

    Article  CAS  PubMed  Google Scholar 

  35. P. Mulatero, F. Rabbia, A. Milan, C. Paglieri, F. Morello, L. Chiandussi, F. Veglio, Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertens. (Dallas, Tex. 1979) 40, 897–902 (2002)

    Article  CAS  Google Scholar 

  36. A. Łebek-Szatańska, L. Papierska, P. Glinicki, W. Zgliczyński, Withdrawal of all medications is not necessary for accurate screening for primary aldosteronism: preliminary results. Pol. Arch. Intern. Med. 131, 578–81 (2021)

    PubMed  Google Scholar 

  37. P. Mulatero, C. Bertello, F. Veglio, S. Monticone, Approach to the patient on antihypertensive therapy: screen for primary aldosteronism. J. Clin. Endocrinol. Metab. 107, 3175–81 (2022)

    Article  PubMed  Google Scholar 

  38. A. Vaidya, R.M. Carey, Evolution of the primary aldosteronism syndrome: Updating the approach. J. Clin. Endocrinol. Metab. 105, 3771–83 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  39. M. Solar, E. Malirova, M. Ballon, R. Pelouch, J. Ceral, Confirmatory testing in primary aldosteronism: Extensive medication switching is not needed in all patients. Eur. J. Endocrinol. 166, 679–86 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. G.P. Rossi, G. Ceolotto, G. Rossitto, G. Maiolino, M. Cesari, T.M. Seccia, Effects of mineralocorticoid and AT1 receptor antagonism on the aldosterone-renin ratio in primary aldosteronism—the EMIRA wtudy. J. Clin. Endocrinol. Metab. 105, 2060–7 (2020)

    Article  Google Scholar 

  41. Y. Tezuka, A.F. Turcu, Mineralocorticoid receptor antagonists decrease the rates of positive screening for primary aldosteronism. Endocr. Pract. 26, 1416–24 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  42. M. Araujo-Castro, J.G. Ruiz-Sánchez, P. Parra Ramírez, P. Martín Rojas-Marcos, A. Aguilera-Saborido, J.F. Gómez Cerezo, N. López Lazareno, M.E. Torregrosa Quesada, J. Gorrin Ramos, J. Oriola, E. Poch, A. Oliveras, J.V. Méndez Monter, I. Gómez Muriel, M.R. Bella-Cueto, E. Mercader Cidoncha, I. Runkle, F.A. Hanzu, and S. A. of S. (AEC) In representation of the following medical Spanish societies: Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology S, Endocrine (2024).

  43. A. Vaidya, G.L. Hundemer, K. Nanba, W.W. Parksook, J.M. Brown, Primary aldosteronism: State-of-the-art review. Am. J. Hypertens. 35, 967–88 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. F. Buffolo, S. Monticone, A. Pecori, J. Pieroni, I. Losano, G. Cavaglià, M. Tetti, F. Veglio, P. Mulatero, The spectrum of low-renin hypertension. Best. Pract. Res. Clin. Endocrinol. Metab. 34, 101399 (2020)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thanks to HUFJD clinicians for their support and team work.

Author information

Authors and Affiliations

  1. Endocrinology Department. Hospital Universitario Fundación Jiménez Díaz, 28040, Madrid, Spain

    Jorge Gabriel Ruiz-Sánchez, Álvaro Fernández Sánchez & Diego Meneses

  2. Instituto de Investigación Sanitaria Fundación Jiménez-Díaz (IIS-FJD), Universidad Autónoma de Madrid (UAM), Hospital Universitario Fundación Jiménez Díaz, 28040, Madrid, Spain

    Jorge Gabriel Ruiz-Sánchez

Authors
  1. Jorge Gabriel Ruiz-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Álvaro Fernández Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diego Meneses
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: J.G.R.-S., D.M.; Methodology: J.G.R.-S.; Validation: J.G.R.-S., D.M.; Formal analysis: J.G.R.-S.; Investigation: J.G.R.-S., A.F.S., D.M.; Writing—Original Draft Preparation: J.G.R.-S.; Writing—Review & Editing: J.G.R.-S., A.F.S., D.M.; Supervision and reviewing: J.G.R.-S., D.M.. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Jorge Gabriel Ruiz-Sánchez.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruiz-Sánchez, J.G., Fernández Sánchez, Á. & Meneses, D. Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests. Endocrine (2024). https://doi.org/10.1007/s12020-024-03798-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12020-024-03798-0

Keywords

Search

Navigation