Evaluation of an Aldosterone Radioimmunoassay: The Renin—Angiotensin—Aldosterone Axis as a Function of Sex and Age

Abstract

SUMMARY.A highly specific radioimmunoassay for aldosterone in plasma has been developed utilising extraction from plasma into dichloromethane, an antiserum raised to aldosterone-3-carboxy-methyloxime-BSA and a radio-iodinated derivative of aldosterone. The plasma values obtained after only extraction correlated very well with the results following chromatography over celite. The within-and between-batch variations for plasma pools ranged between 5 and 15%. The range obtained, HXl-1806 pmoVL for 96 random upright subjects, was comparable to others reported. Measurement of plasma aldosterone and plasma renin activity in these subjects showed that both these parameters are higher in subjects under 40 years of age than in those over 40. In addition, plasma aldosterone levels are higher in women than in men even though their plasma renin activity levels are similar. The plasma aldosterone/renin activity ratios which provide an index of adrenal sensitivity to stimulation, are lower in men than in women. The findings in this study suggest that higher aldosterone levels in younger subjects are associated with greater stimulation of the adrenals than in older subjects and that the adrenal is more sensitive in women than in men.The most widely used method for the measurement of aldosterone in plasma is radioimmunoassay. Since the concentration of aldosterone in plasma samples is very low compared to the levels of some potentially cross-reacting steroids, chromatographic purification of samples prior to assay provides the most accurate results especially in samples with abnormal steroid profiles. I, 2 Simpler methods for the purification of samples prior to assay have been reportedr? all of which require extraction into organic solvents. Over the past 10 years direct radioimmunoassays for aldosterone have been promoted. Ogihara et al.6 employed a highly specific antiserum in such an assay. Al Dujaili and Edwards? claimed that a low assay pH and the use of a radio-iodinated derivative greatly enhanced the avidity of the antiserum for aldosterone relative to the other steroids, thus providing a useful direct assay for aldosterone. These direct methods are convenient, cheap and fast, and were reported to give results which were similar to, and correlated with, results obtained following chromatography. However, we were unable to confirm the dramatic pH effect on antibody specificity described by Al Dujaili and Edwards? using the same antiserum and the same assay systemour findings were similar to those of Lun et al. 8 In this study we describe the evaluation of antisera for use in an aldosterone radioimmunoassay using a radio-iodinated aldosterone derivative, and the subsequent development of a highly specific, convenient routine assay for aldosterone following extraction from plasma. This assay was used to examine the reninangiotensin-aldosterone axis in an ambulatory random population. Plasma aldosterone levels are higher in women than in men-this is due to greater adrenal sensitivity to stimulation in women. Plasma al...

Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: need for a standardized protocol

“…However, numerous studies have shown an overlap between aldosterone levels in 24-h urine collections in patients with primary aldosteronism and with essential hypertension [22][23][24], although the urinary determination of tetrahydroaldosterone seems to be more promising, as recently proposed [25]. APA, Aldosterone-producing adenoma; IHA: idiopathic hyperaldosteronism; PRA, plasma renin activity.…”

Diagnosis under Random Conditions of All Disorders of the Renin-Angiotensin-Aldosterone Axis, Including Primary Hyperaldosteronism

“…We have considerably expanded this concept. To establish the usefullness of the PA/PRA ratio in the screening for aldosterone disorders, it was necessary to expand our experience with normal subjects, which had previously been confined to upright values (8), to a variety of stable and unstable conditions. Although PA and PRA varied significantly with lying and standing and with variations in salt intake, the PA/PRA ratio was constant.…”

“…Additional samples were obtained from some in-patient subjects after overnight recumbency. PA was measured using a highly specific RIA, previously described from this laboratory (8). PRA was measured using a CEA Sorin (Vercielli, Italy) kit to estimate the generation of angiotensin-I by RIA (10).…”

“…In a preliminary study we measured the random upright PA and PA/PRA ratio values in 98 healthy volunteers (8); these were used to derive reference ranges for PA and the PA/PRA ratio. Ten healthy volunteer subjects, aged 18-30 yr, were studied under different conditions on 2 separate occasions.…”

Reninoma: The Importance of Renal Vein Renin Ratios for Lateralisation and Diagnosis

“…Serum creatinine was normal and plasma renin activity (PRA) and aldosterone levels after 2 h of upright posture were measured at 31.9 ng/ml/h (upper limit of normal in young women: 10.5 ng/ml/h [5]) and 19.9 ng/dl (upper limit of normal in young women: 43.6 ng/dl [5]), respectively, while taking captopril 12.5 mg twice daily. Intravenous pyelography, renal angiography and renal CT were normal.…”