Appraisal of Modified Tests for Diagnosis and Treatment of Primary Aldosteronism: A Single Center Experience
Main Article Content
Abstract
Introduction: Primary aldosteronism (PA), the most common endocrine cause of secondary hypertension, is generally under diagnosed using current diagnostic tests.
Objective: To present our findings, based on studies using modified diagnostic tests, on the diagnosis, prevalence and treatment of PA.
Design and Methods: We prospectively studied 992 hypertensive patients and 278 matched controls. Participants underwent conventional confirmatory tests for the diagnosis of PA modified by the addition of dexamethasone including the Fludrocortisone Dexamethasone Suppression Test (FDST), the Dexamethasone Captopril Valsartan Test (DCVT) and the Dexamethasone Saline Infusion Test (DSIT). Normal cut-offs of basal aldosterone-to-renin ratio and post-test (FDST, DCVT and DSIT) aldosterone levels and aldosterone-to-renin ratio were calculated from the control groups, who had normal adrenal imaging.
Results: Hypertensive patients had significantly higher baseline blood pressure and lower serum potassium levels compared to controls. Using the basal aldosterone-to-renin ratio as screening test, the prevalence of PA was 17.8%. After applying the modified tests to all patients, the prevalence of PA was 33.4%. Targeted treatment with Mineralocorticoid Receptor Antagonists was administered in 252 hypertensives, with bilateral PA; 188 (74.6%) of them obtained a biochemical response and normalization of blood pressure. Unilateral disease had 48 patients who underwent laparoscopic adrenalectomy obtaining a biochemical success rate was 94%.
Conclusion: Our modified methodology and the use of normotensive controls for calculation of normal cut-offs of aldosterone suppression, significantly improves the sensitivity and specificity of the existing tests on the diagnosis of PA, allowing the detection of milder forms.
Article Details
How to Cite
G., Piaditis et al.
Appraisal of Modified Tests for Diagnosis and Treatment of Primary Aldosteronism: A Single Center Experience.
Medical Research Archives, [S.l.], v. 12, n. 12, dec. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6161>. Date accessed: 06 jan. 2025.
doi: https://doi.org/10.18103/mra.v12i12.6161.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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3. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/JC.2015-4061
4. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ???non-selective??? screening of hypertensive patients. J Hypertens. 2003;21(11):2149-2157. doi:10.1097/00004872-200311000-00025
5. Rossi GP, Bernini G, Caliumi C, et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients. J Am Coll Cardiol. 2006;48(11):2293-2300. doi:10.1016/j.jacc.2006.07.059
6. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66(5):607-618. doi:10.1111/j.1365-2265.2007.02775.x
7. Douma S, Petidis K, Doumas M, et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. The Lancet. 2008;371(9628):1921-1926. doi:10.1016/S0140-6736(08)60834-X
8. Stowasser M. Update in Primary Aldosteronism. J Clin Endocrinol Metab. 2009;94(10):3623-3630. doi:10.1210/jc.2009-1399
9. 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. Eur J Endocrinol. 2015;172(5):R191-R203. doi:10.1530/EJE-14-0537
10. Baudrand R, Guarda FJ, Fardella C, et al. Continuum of Renin-Independent Aldosteronism in Normotension. Hypertension. 2017;69(5):950-956. doi:10.1161/HYPERTENSIONAHA.116.08952
11. Brown JM, Siddiqui M, Calhoun DA, et al. The Unrecognized Prevalence of Primary Aldosteronism. Ann Intern Med. 2020;173(1):10-20. doi:10.7326/M20-0065
12. Levy DG, Rocha R, Funder JW. Distinguishing the Antihypertensive and Electrolyte Effects of Eplerenone. J Clin Endocrinol Metab. 2004;89(6):2736-2740. doi:10.1210/jc.2003-032149
13. 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(12):827-833. doi:10.1055/a-1236-4869
14. Piaditis GP, Kaltsas GA, Androulakis II, et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol (Oxf). 2009;71(6):772-778. doi:10.1111/j.1365-2265.2009.03551.x
15. Gouli A, Kaltsas G, Tzonou A, et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest. 2011;41(11):1227-1236. doi:10.1111/j.1365-2362.2011.02531.x
16. Tsiavos V, Markou A, Papanastasiou L, et al. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol. 2016;175(1):21-28. doi:10.1530/EJE-16-0003
17. Markou A, Pappa T, Kaltsas 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. J Clin Endocrinol Metab. 2013;98(4):1409-1416. doi:10.1210/JC.2012-3353
18. Fassnacht M, Tsagarakis S, Terzolo M, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189(1):G1-G42. doi:10.1093/EJENDO/LVAD066
19. Fountoulakis S, Papanastasiou L, Voulgaris N, et al. Salt intake in mineralocorticoid receptor antagonist-treated primary aldosteronism: foe or ally? Hormones. 2020;19(2):223-232. doi:10.1007/s42000-019-00167-9
20. Papanastasiou L, Markou A, Pappa T, et al. Primary aldosteronism in hypertensive patients: clinical implications and target therapy. Eur J Clin Invest. 2014;44(8):697-706. doi:10.1111/eci.12286
21. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ???non-selective??? screening of hypertensive patients. J Hypertens. 2003;21(11):2149-2157. doi:10.1097/00004872-200311000-00025
22. Rossi GP, Bernini G, Caliumi C, et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients. J Am Coll Cardiol. 2006;48(11):2293-2300. doi:10.1016/j.jacc.2006.07.059
23. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66(5):607-618. doi:10.1111/j.1365-2265.2007.02775.x
24. Stowasser M. Update in Primary Aldosteronism. J Clin Endocrinol Metab. 2009;94(10):3623-3630. doi:10.1210/jc.2009-1399
25. Ferreira NS, Tostes RC, Paradis P, Schiffrin EL. Aldosterone, Inflammation, Immune System, and Hypertension. Am J Hypertens. 2021;34(1):15-27. doi:10.1093/ajh/hpaa137
26. Turcu AF, Yang J, Vaidya A. Primary aldosteronism — a multidimensional syndrome. Nat Rev Endocrinol. 2022;18(11):665-682. doi:10.1038/s41574-022-00730-2
27. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management. Endocr Rev. 2004;25(2):309-340. doi:10.1210/er.2002-0031
28. KLOOS RT, GROSS MD, FRANCIS IR, KOROBKIN M, SHAPIRO B. Incidentally Discovered Adrenal Masses*. Endocr Rev. 1995;16(4):460-484. doi:10.1210/edrv-16-4-460
29. Arvat E, Di Vito L, Lanfranco F, et al. Stimulatory Effect of Adrenocorticotropin on Cortisol, Aldosterone, and Dehydroepiandrosterone Secretion in Normal Humans: Dose-Response Study*. J Clin Endocrinol Metab. 2000;85(9):3141-3146. doi:10.1210/jcem.85.9.6784
30. Markou A, Kaltsas GA, Papanastasiou L, et al. Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas. Eur J Endocrinol. 2022;186(2):265-273. doi:10.1530/EJE-21-0625
31. Baudrand R, Guarda FJ, Torrey J, Williams G, Vaidya A. Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism. J Clin Endocrinol Metab. 2016;101(11):3989-3996. doi:10.1210/jc.2016-1963
32. Peng KY, Liao HW, Chan CK, et al. Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success. Hypertension. 2020;76(5):1537-1544. doi:10.1161/HYPERTENSIONAHA.120.15328
33. Nakamura Y, Maekawa T, Felizola SJA, et al. Adrenal CYP11B1/2 expression in primary aldosteronism: Immunohistochemical analysis using novel monoclonal antibodies. Mol Cell Endocrinol. 2014;392(1-2):73-79. doi:10.1016/j.mce.2014.05.002
34. Arlt W, Lang K, Sitch AJ, et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2017;2(8). doi:10.1172/jci.insight.93136
35. Fallo F, Sonino N. Should we evaluate for cardiovascular disease in patients with Cushing’s syndrome? Clin Endocrinol (Oxf). 2009;71(6):768-771. doi:10.1111/j.1365-2265.2009.03610.x
36. Androulakis II, Kaltsas GA, Kollias GE, et al. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab. 2014;99(8):2754-2762. doi:10.1210/JC.2013-4064
37. Nakajima Y, Yamada M, Taguchi R, et al. Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion. J Clin Endocrinol Metab. 2011;96(8):2512-2518. doi:10.1210/JC.2010-2743
38. Tang L, Li X, Wang B, et al. Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism. Int J Endocrinol. 2018;2018:1-9. doi:10.1155/2018/4920841
39. Ohno Y, Sone M, Inagaki N, et al. Latent Autonomous Cortisol Secretion From Apparently Nonfunctioning Adrenal Tumor in Nonlateralized Hyperaldosteronism. J Clin Endocrinol Metab. 2019;104(10):4382-4389. doi:10.1210/jc.2018-02790
40. Inoue K, Kitamoto T, Tsurutani Y, Saito J, Omura M, Nishikawa T. Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies. Front Endocrinol (Lausanne). 2021;12. doi:10.3389/fendo.2021.645488
41. Williams TA, Lenders JWM, Mulatero P, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5(9):689-699. doi:10.1016/S2213-8587(17)30135-3
42. Schneider H, Williams TA, Heinrich DA, Lechner B, Reincke M. Primary aldosteronism long-term outcome: Medical versus surgical therapy. Curr Opin Endocr Metab Res. 2019;8:132-138. doi:10.1016/j.coemr.2019.08.008
43. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061
44. Williams TA, Burrello J, Sechi LA, et al. Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism. Hypertension. 2018;72(3):641-649. doi:10.1161/HYPERTENSIONAHA.118.11382
2. Schirpenbach C, Reincke M. Primary aldosteronism: current knowledge and controversies in Conn’s syndrome. Nat Clin Pract Endocrinol Metab. 2007;3(3):220-227. doi:10.1038/ncpendmet0430
3. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/JC.2015-4061
4. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ???non-selective??? screening of hypertensive patients. J Hypertens. 2003;21(11):2149-2157. doi:10.1097/00004872-200311000-00025
5. Rossi GP, Bernini G, Caliumi C, et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients. J Am Coll Cardiol. 2006;48(11):2293-2300. doi:10.1016/j.jacc.2006.07.059
6. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66(5):607-618. doi:10.1111/j.1365-2265.2007.02775.x
7. Douma S, Petidis K, Doumas M, et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. The Lancet. 2008;371(9628):1921-1926. doi:10.1016/S0140-6736(08)60834-X
8. Stowasser M. Update in Primary Aldosteronism. J Clin Endocrinol Metab. 2009;94(10):3623-3630. doi:10.1210/jc.2009-1399
9. 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. Eur J Endocrinol. 2015;172(5):R191-R203. doi:10.1530/EJE-14-0537
10. Baudrand R, Guarda FJ, Fardella C, et al. Continuum of Renin-Independent Aldosteronism in Normotension. Hypertension. 2017;69(5):950-956. doi:10.1161/HYPERTENSIONAHA.116.08952
11. Brown JM, Siddiqui M, Calhoun DA, et al. The Unrecognized Prevalence of Primary Aldosteronism. Ann Intern Med. 2020;173(1):10-20. doi:10.7326/M20-0065
12. Levy DG, Rocha R, Funder JW. Distinguishing the Antihypertensive and Electrolyte Effects of Eplerenone. J Clin Endocrinol Metab. 2004;89(6):2736-2740. doi:10.1210/jc.2003-032149
13. 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(12):827-833. doi:10.1055/a-1236-4869
14. Piaditis GP, Kaltsas GA, Androulakis II, et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol (Oxf). 2009;71(6):772-778. doi:10.1111/j.1365-2265.2009.03551.x
15. Gouli A, Kaltsas G, Tzonou A, et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest. 2011;41(11):1227-1236. doi:10.1111/j.1365-2362.2011.02531.x
16. Tsiavos V, Markou A, Papanastasiou L, et al. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol. 2016;175(1):21-28. doi:10.1530/EJE-16-0003
17. Markou A, Pappa T, Kaltsas 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. J Clin Endocrinol Metab. 2013;98(4):1409-1416. doi:10.1210/JC.2012-3353
18. Fassnacht M, Tsagarakis S, Terzolo M, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189(1):G1-G42. doi:10.1093/EJENDO/LVAD066
19. Fountoulakis S, Papanastasiou L, Voulgaris N, et al. Salt intake in mineralocorticoid receptor antagonist-treated primary aldosteronism: foe or ally? Hormones. 2020;19(2):223-232. doi:10.1007/s42000-019-00167-9
20. Papanastasiou L, Markou A, Pappa T, et al. Primary aldosteronism in hypertensive patients: clinical implications and target therapy. Eur J Clin Invest. 2014;44(8):697-706. doi:10.1111/eci.12286
21. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ???non-selective??? screening of hypertensive patients. J Hypertens. 2003;21(11):2149-2157. doi:10.1097/00004872-200311000-00025
22. Rossi GP, Bernini G, Caliumi C, et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients. J Am Coll Cardiol. 2006;48(11):2293-2300. doi:10.1016/j.jacc.2006.07.059
23. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66(5):607-618. doi:10.1111/j.1365-2265.2007.02775.x
24. Stowasser M. Update in Primary Aldosteronism. J Clin Endocrinol Metab. 2009;94(10):3623-3630. doi:10.1210/jc.2009-1399
25. Ferreira NS, Tostes RC, Paradis P, Schiffrin EL. Aldosterone, Inflammation, Immune System, and Hypertension. Am J Hypertens. 2021;34(1):15-27. doi:10.1093/ajh/hpaa137
26. Turcu AF, Yang J, Vaidya A. Primary aldosteronism — a multidimensional syndrome. Nat Rev Endocrinol. 2022;18(11):665-682. doi:10.1038/s41574-022-00730-2
27. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management. Endocr Rev. 2004;25(2):309-340. doi:10.1210/er.2002-0031
28. KLOOS RT, GROSS MD, FRANCIS IR, KOROBKIN M, SHAPIRO B. Incidentally Discovered Adrenal Masses*. Endocr Rev. 1995;16(4):460-484. doi:10.1210/edrv-16-4-460
29. Arvat E, Di Vito L, Lanfranco F, et al. Stimulatory Effect of Adrenocorticotropin on Cortisol, Aldosterone, and Dehydroepiandrosterone Secretion in Normal Humans: Dose-Response Study*. J Clin Endocrinol Metab. 2000;85(9):3141-3146. doi:10.1210/jcem.85.9.6784
30. Markou A, Kaltsas GA, Papanastasiou L, et al. Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas. Eur J Endocrinol. 2022;186(2):265-273. doi:10.1530/EJE-21-0625
31. Baudrand R, Guarda FJ, Torrey J, Williams G, Vaidya A. Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism. J Clin Endocrinol Metab. 2016;101(11):3989-3996. doi:10.1210/jc.2016-1963
32. Peng KY, Liao HW, Chan CK, et al. Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success. Hypertension. 2020;76(5):1537-1544. doi:10.1161/HYPERTENSIONAHA.120.15328
33. Nakamura Y, Maekawa T, Felizola SJA, et al. Adrenal CYP11B1/2 expression in primary aldosteronism: Immunohistochemical analysis using novel monoclonal antibodies. Mol Cell Endocrinol. 2014;392(1-2):73-79. doi:10.1016/j.mce.2014.05.002
34. Arlt W, Lang K, Sitch AJ, et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2017;2(8). doi:10.1172/jci.insight.93136
35. Fallo F, Sonino N. Should we evaluate for cardiovascular disease in patients with Cushing’s syndrome? Clin Endocrinol (Oxf). 2009;71(6):768-771. doi:10.1111/j.1365-2265.2009.03610.x
36. Androulakis II, Kaltsas GA, Kollias GE, et al. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab. 2014;99(8):2754-2762. doi:10.1210/JC.2013-4064
37. Nakajima Y, Yamada M, Taguchi R, et al. Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion. J Clin Endocrinol Metab. 2011;96(8):2512-2518. doi:10.1210/JC.2010-2743
38. Tang L, Li X, Wang B, et al. Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism. Int J Endocrinol. 2018;2018:1-9. doi:10.1155/2018/4920841
39. Ohno Y, Sone M, Inagaki N, et al. Latent Autonomous Cortisol Secretion From Apparently Nonfunctioning Adrenal Tumor in Nonlateralized Hyperaldosteronism. J Clin Endocrinol Metab. 2019;104(10):4382-4389. doi:10.1210/jc.2018-02790
40. Inoue K, Kitamoto T, Tsurutani Y, Saito J, Omura M, Nishikawa T. Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies. Front Endocrinol (Lausanne). 2021;12. doi:10.3389/fendo.2021.645488
41. Williams TA, Lenders JWM, Mulatero P, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5(9):689-699. doi:10.1016/S2213-8587(17)30135-3
42. Schneider H, Williams TA, Heinrich DA, Lechner B, Reincke M. Primary aldosteronism long-term outcome: Medical versus surgical therapy. Curr Opin Endocr Metab Res. 2019;8:132-138. doi:10.1016/j.coemr.2019.08.008
43. Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061
44. Williams TA, Burrello J, Sechi LA, et al. Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism. Hypertension. 2018;72(3):641-649. doi:10.1161/HYPERTENSIONAHA.118.11382