Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2024 Oct 24

PMID 39445045

Authors

Yug Garg

Madhumati S Vaishnav

Nidhi Garg

Reshma B Vijay

Leena Lekkala

Siddhartha Dinesha

Pushpa Ravikumar

Thummala Kamala

Kavitha Muniraj

Sathyanarayana Srikanta

Affiliations

Soon will be listed here.

Abstract

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

References

Scholl U . Genetics of Primary Aldosteronism. Hypertension. 2022; 79(5):887-897. PMC: 8997684. DOI: 10.1161/HYPERTENSIONAHA.121.16498. View

Byrd J, Turcu A, Auchus R . Primary Aldosteronism: Practical Approach to Diagnosis and Management. Circulation. 2018; 138(8):823-835. PMC: 6205759. DOI: 10.1161/CIRCULATIONAHA.118.033597. View

Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N . Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet. 2008; 371(9628):1921-6. DOI: 10.1016/S0140-6736(08)60834-X. View

Memon S, Bandgar T . Update on Primary Aldosteronism: Time to Screen All Hypertensives. J Assoc Physicians India. 2024; 72(1):11-12. DOI: 10.59556/japi.71.0430. View

Zennaro M, Boulkroun S, Fernandes-Rosa F . Pathogenesis and treatment of primary aldosteronism. Nat Rev Endocrinol. 2020; 16(10):578-589. DOI: 10.1038/s41574-020-0382-4. View

Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N . Guidelines for the diagnosis and treatment of primary aldosteronism--the Japan Endocrine Society 2009. Endocr J. 2011; 58(9):711-21. DOI: 10.1507/endocrj.ej11-0133. View

Stavropoulos K, Papadopoulos C, Koutsampasopoulos K, Lales G, Mitas C, Doumas M . Mineralocorticoid Receptor Antagonists in Primary Aldosteronism. Curr Pharm Des. 2019; 24(46):5508-5516. DOI: 10.2174/1381612825666190311130138. View

Vaidya A, Mulatero P, Baudrand R, Adler G . The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment. Endocr Rev. 2018; 39(6):1057-1088. PMC: 6260247. DOI: 10.1210/er.2018-00139. View

Bioletto F, Lopez C, Bollati M, Arata S, Procopio M, Ponzetto F . Predictive performance of aldosterone-to-renin ratio in the diagnosis of primary aldosteronism in patients with resistant hypertension. Front Endocrinol (Lausanne). 2023; 14:1145186. PMC: 10200868. DOI: 10.3389/fendo.2023.1145186. View

10.

Brown J, Robinson-Cohen C, Luque-Fernandez M, Allison M, Baudrand R, Ix J . The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study. Ann Intern Med. 2017; 167(9):630-641. PMC: 5920695. DOI: 10.7326/M17-0882. View

11.

Parksook W, Yozamp N, Hundemer G, Moussa M, Underhill J, Fudim T . Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism. Am J Hypertens. 2021; 35(6):561-571. PMC: 9890245. DOI: 10.1093/ajh/hpab189. View

12.

Young W, Stanson A, Thompson G, Grant C, Farley D, van Heerden J . Role for adrenal venous sampling in primary aldosteronism. Surgery. 2005; 136(6):1227-35. DOI: 10.1016/j.surg.2004.06.051. View

13.

Rossi G, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C . A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006; 48(11):2293-300. DOI: 10.1016/j.jacc.2006.07.059. View

14.

Williams B, MacDonald T, Morant S, Webb D, Sever P, McInnes G . Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015; 386(10008):2059-2068. PMC: 4655321. DOI: 10.1016/S0140-6736(15)00257-3. View

15.

Rossi G . A comprehensive review of the clinical aspects of primary aldosteronism. Nat Rev Endocrinol. 2011; 7(8):485-95. DOI: 10.1038/nrendo.2011.76. View

16.

Bioletto F, Bollati M, Lopez C, Arata S, Procopio M, Ponzetto F . Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight. Int J Mol Sci. 2022; 23(9). PMC: 9100181. DOI: 10.3390/ijms23094803. View

17.

Funder J, Carey R, Mantero F, Murad M, Reincke M, Shibata H . The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101(5):1889-916. DOI: 10.1210/jc.2015-4061. View

18.

Jaffe G, Gray Z, Krishnan G, Stedman M, Zheng Y, Han J . Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study. Hypertension. 2020; 75(3):650-659. DOI: 10.1161/HYPERTENSIONAHA.119.14359. View

19.

Vaidya A, Carey R . Evolution of the Primary Aldosteronism Syndrome: Updating the Approach. J Clin Endocrinol Metab. 2020; 105(12). PMC: 7899564. DOI: 10.1210/clinem/dgaa606. View

20.

Williams T, Reincke M . Pathophysiology and histopathology of primary aldosteronism. Trends Endocrinol Metab. 2021; 33(1):36-49. DOI: 10.1016/j.tem.2021.10.002. View