Captopril suppression: limitations for confirmation of primary aldosteronism

Abstract

Introduction: The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means.

Methods: A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR.

Results: At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test.

Conclusion: The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA.

Keywords

Aldosterone captopril hypertension primary aldosteronism renin

Get full access to this article

View all access options for this article.

References

Stowasser M. and Gordon RD Primary aldosteronism. Best Pract Res Clin Endocrinol Metab 2003; 17: 591-605.

Young WF Jr. Mini review: Primary aldosteronism- changing concepts in diagnosis and treatment. Endocrinology 2003 ; 144: 2208-2213.

Funder JW , Carey RM , Fardella C. , Gomez-Sanchez CE , Mantero F. , Stowasser M. et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: An Endocrine Society Clinical Practice Guidline. JCEM 2008; 93; 3266-3281.

Nadar S. , Lip GY and Beevers DG Primary hyperaldosteronism. Ann Clin Biochem. 2003; 40: 439-452.

Conn JW Presidential address: Part1. Painting background, Part II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med 1955 ; 45: 3-15.

Gordon RD , Klemm SA , Stowasser M. , Tunny TJ , Storie WJ and Rutherford JC

How common is primary aldosteronism? Is it the most frequent form of curable hypertension?

J Hypertens 1993; 11: S310-S311.

Lim PO , Rodgers P. , Cardale K. , Watson AD and MacDonald TM Potentially high prevalence of primary aldosteronism in a primary care population . Lancet 1999; 353: 40.

Mulatero P. , Stowasser M. , Loh KC , Fardella CE , Gordon RD , Mosso L. et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centres from five continents. J Clin Endocrinol Metab 2004; 89: 1045-1050.

Bencherit S. , Bernheim J. and Podjarny E. Normokalemic hyperaldosteronism in patients with resistant hypertension. Israel Med Assoc J 2002; 4: 17-20.

10.

Westerdahl C. , Bergenfelz A. , Isaksson A. , Wihl A. , Nerbrand C. and Valdemarsson S. High frequency of primary aldosteronism among hypertensive patients from a primary care area in Sweden . Scand J Prim Health Care 2006; 24: 154-159.

11.

Perschel FH , Schemer R. , Seiler L. , Reincke M. , Deinum J. and Maser-Gluth C. Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays. Clin Chem 2004; 50: 1650-1655.

12.

Cartledge S. and Lawson N. Aldosterone and renin measurements. Ann Clin Biochem 2000; 37: 262-278.

13.

Unger N. , Lopez Schmidt I. , Pitt C. , Walz MK , Philipp T. , Mann K. , et al. Comparison of active renin concentration and plasma renin activity for the diagnosis of primary hyperaldosteronism in patients with an adrenal mass. Eur J Endocrinol 2004; 150: 517-523.

14.

Montori VM and Young WF Jr. Use of plasma aldosterone concenteration- to plasma renin activity ratio as a screening test for primary aldosteronism. A systemic review of the literature. Endocrinol Metab Clin North Am 2002; 31: 619-632.

15.

Giacchetti G. , Ronoconi V. , Lucarelli G. , Boscaro M. and Mantero F. Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: Need for a standardized protocol . J Hypertens 2006; 24: 737-745.

16.

Hiramatsu K. , Yamada T. and Yukimara Y. A screening test to identify aldosterone- producing adenomas by measuring plasma renin activity. Results in hypertensive patients. Arch Int Med 1981; 141: 1589-1593.

17.

Westerdahl C. , Bergenfelz B. , Larsson J. , Nerbrand C. , Valdemarsson S. , Wihl A. et al. Re-evaluation of the fludrocortisone test: duration, NaCl supplementation and cut-off limits for aldosterone. Scand J Clin Lab Invest 2008; 24: 1-8.

18.

Lyons DF , Kem DC , Brown RD , Hansson CS and Carollo MI Single dose captopril as a diagnosic test for primary aldosteronism. J Clin Endocrinol Metab 1983; 57: 892-896.

19.

Stowasser M. , Gordon RD , Rutherford JC , Nikwan NZ , Daunt N. and Slater GJ Diagnosis and management of primary aldosteronism . J Renin Angiotensin Aldosterone Syst 2001 ; 2: 156-169.

20.

Young W. F Primary aldosteronism: Renaissance of a syndrome. Clin Endocrinol 2007; 66: 607-618.

21.

Rossi GP , Belfiore A. , Bernini G. , Desideri G. et al. Comparison of the Captopril and the saline infusion test for excluding aldosterone -producing adenoma. Hypertension 2007; 50: 424-431.

22.

Agharzii M. , Douville P. , Grose J. et al. Captopril suppression versus salt loading in confirming primary aldosteronism. Hypertension 2001; 37:1440-1443.

23.

Castro O. , Yu X. and Kern D. Diagnostic value of the post Captopril test in primary aldosteronism. Hypertension 2002; 39:935-938.

24.

Rossi E. , Regolisti G. , Negro A. , Sani C. , Davoli S. and Perazzoli F. High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to plasma renin ratio as a screening test among Italian hypertensives. Am J Hyperten 2002;15:896-902.

25.

Ahokoski O. , Virtanen A. , Kariristo V. , Scheinin H. , Huupponen R. and Irjala K. Biological day-to-day variation and reference change limits of serum cortisol and aldosterone in healthy young men on unrestricted diets. Clin Chem 1999; 45: 1097-1099.

26.

Conell J. , Scott M. MacKenzie E. , Freel M. , Fraser R. and Davis E. A lifetime of aldosterone excess: Long term consequences of altered regulation of aldosterone production for cardiovascular function. Endocrine Reviews 2008; 29: 133-154.

27.

Mulatero P. , Bertello C. , Garrone C. , Rossato D. , Mengozzi G. , Verhovez A. et al. Captopril test can give misleading results in patients with suspect primary aldosteronism. Hyperpension 2007; 50: e26-e27.

28.

Padfield PL , Brown JJ , Davies D. , Fraser R. , Lever AF , Morton JJ et al. The myth of idiopathic hyperaldosteronism . Lancet 1981 2: 83-84;

29.

Mantero F. , Fallo F. , Opocher G. , Armanini D. and Boscaro M. , Scaroni C. Effect of angiotensin II and converting enzyme inhibitor (captopril) on blood pressure, plasma renin activity and aldosterone in primary aldosteronism. Clin Sci (Lond) 1981; 61: 289s-293s.

30.

Hambling C. , Jung RT , Gunn A. , Browning MC and Bartlett WA Re-evaluation of the captopril test for the diagnosis of primary hyperaldosteronism. Clin Endocrinol( Oxf) 1988; 36: 499-503.

31.

Mantero F. , Bedeno O. and Opocher G.

Does dynamic testing have a place in the modern assessment of endocrine hypertension?

J Renin Angiotensin Aldosterone Syst 2001 ; 2: 156-169.

32.

Naomi S. , Iwaoka T. , Umeda T. , Inoue J. , Hamasaki S. , Miura F. et al. Clinical evaluation of the captopril screening test for primary aldosteronism. Jpn Heart J 1985; 26: 549-556.