Single Dose Captopril as a Diagnostic Test for Primary Aldosteronism*

Abstract

Most diagnostic tests for primary aldosteronism use maneuvers to expand the extracellular fluid volume, thereby suppressing the renin-angiotensin system. This results in a decline in plasma aldosterone concentrations in normal subjects and essential hypertension (EH) patients, but not in patients with primary aldosteronism. Captopril blocks angiotensin II synthesis and might be used as a diagnostic test for primary aldosteronism. We have measured plasma aldosterone concentrations 2 h after the administration of 25 mg captopril in 9 normotensive subjects, 10 patients with EH, and 12 patients with primary aldosteronism while they were ingesting an unrestricted diet. The plasma aldosterone concentration decreased to less than 15 ng/dl in all normotensive subjects and in 9 of 10 patients with EH, but remained greater than 15 ng/dl in 4 of 5 patients with idiopathic hyperaldosteronism and in all patients with an aldosterone-producing adenoma. The aldosterone to renin ratio was greater than 50 in 4 of 5 patients with idiopathic hyperaldosteronism and in all adenoma patients, but less than 50 in all normotensive subjects and EH patients. A nomogram comparing the plasma aldosterone concentration with the aldosterone to renin ratio clearly separated primary aldosteronism patients from EH patients.

Prevalence of Primary Aldosteronism among Unselected Hypertensive Patients: A Prospective Study Based on the Use of an Aldosterone/Renin Ratio above 25 as a Screening Test

“…The ARR has been advocated as a convenient and effective method to screen for PA, with some limitations concerning a possible reduction of its accuracy by various antihypertensive drugs, posture changes, time of day, potassium levels and renal insufficiency (7)(8)(9). An elevated ARR is not diagnostic by itself and PA must be confirmed by other tests, such as a saline infusion test, fludrocortisone suppression test, captopril test and oral salt loading test, which are able to demonstrate an inappropriate autonomous ALD production (8,(10)(11)(12)(13)(14). The application of the ARR to a broader population of hypertensives has uncovered a higher prevalence of PA in both hypertensive clinic and primary care populations, with prevalence rates ranging from 3% to 32% and most patients being normokalemic (15)(16)(17)(18)(19)(20)(21).…”

Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension

“…Altogether the computation of the ARR, particularly when correlated to the PA value, 30 appears the most robust screening test for primary aldosteronism. 24 Now that plasma aldosterone and renin assessments are readily available in most commercial laboratories and major hospitals at a reasonable cost, measurement of these parameters in simultaneously drawn blood samples is recommended, followed by computation of the ARR (Figure 1).…”

“…[28][29][30] The use of captopril therefore increases the utility of the ARR by increasing specificity and thus decreasing the need for confirmatory testing. In 1983, Lyons et al 30 compared the use of the ARR obtained 2 h after a dose of captopril with results obtained using the 'gold standard' saline infusion. They found that the acute suppression of aldosterone and removal of any negative feedback on circulating levels of renin using the post captopril ARR were as efficacious as the more cumbersome infusion of saline over a 4 h period.…”

“…Thus, the captopril-stimulated ARR seems to have now been confirmed using two different 'goldstandard' salt-loading tests. 30,31 The simple addition of 25 mg oral captopril 2 h before obtaining a second set of blood samples for the ARR, therefore, not only serves as a screening test but also might establish a definitive diagnosis of primary aldosteronism. 32 The specificity of the ARR test is more dependent on demonstrating that the post-captopril ARR remains above 12 (330 if PA in pmol/l), despite the loss of the inhibitory levels of angiotensin II, and the PA fails to be suppressed to less than a definable level (o240-330 pmol/l).…”

A Case of Aldosterone Producing Adenoma Associated with High PRA after Long-Term Angiotensin Converting Enzyme Inhibitor Treatment.

“…Third, ACEIs stimulate renin secretion by inhibiting direct negative feedback of angiotensin II in a normal person. But captopril, one of the ACEIs, was reported not to increase PRA in APA [8], and the unresponsiveness of PRA to captopril administration is there- (AP-RA) [9]. The main characteristic of this adrenal adenoma sub-type is that it resembles IHA.…”