Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites

Abstract

Objective: Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo-and hypokalaemic primary aldosteronism under current antihypertensive medication. Patients and methods: 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide. Results: In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo-and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%). Conclusions: These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo-or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.European Journal of Endocrinology 154 865-873

Indicators of mineralocorticoid excess in the evaluation of primary aldosteronism

“…24,25 The early detection of PA in the hypertensive population is beneficial, because specific treatment approaches improve the associated mortality and morbidity. 1,24,26 If the A PL /PRA ratio is used as a screening tool, the prevalence of PA in hypertensive patients varies between 9 and 13%, depending on the patient population. 2,3,6,13,27,28 However, there is still a lack of consensus regarding the appropriate method for determination of renin.…”

Automated Chemiluminescence-Immunoassay for Aldosterone during Dynamic Testing: Comparison to Radioimmunoassays with and without Extraction Steps

“…We based the diagnosis of PA on the following biochemical criteria (11 ): repeatedly increased aldosterone/ renin ratios (according to cutoff values of the local laboratory using the Adaltis RIA for measurement of aldosterone), increased urinary aldosterone excretion [Ͼ15 g/day, or a previous pathological saline infusion test (serum aldosterone at 240 min Ͼ80 ng/L or 223 nmol/L)]. Differential diagnosis of PA was based on an algorithm (combining the results of computed tomography/magnetic resonance imaging and a posture test) (12 ) and/or selective vein catheterization.…”

Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

“…Here, we want to emphasize that what we refer to as ''aldosterone treatment'' is the more physiological condition when compared with culture conditions in which the hormone is absent. The aldosterone concentration used in our culture media is in the high normal range in the normal population (26). The sodium-induced increase in cell stiffness is most likely linked to cell swelling because in aldosterone-treated endothelium amiloride reverses the increase in cell volume (9) and cell pressure (20).…”