Salivary aldosterone to cortisol ratio: Potential screening tool for primary aldosteronism

Abstract

Increased incidence of primary aldosteronism in the hypertensive population has renewed interest in the role of mineralocorticoids in cardiovascular diseases. Therefore, a simple non-invasive screening tool to detect hypersecretion of aldosterone would be useful. We have previously established and validated a highly sensitive immunoassay for the detection aldosterone in saliva. Given that autonomous hypersecretion of aldosterone should be largely independent from pituitary stimulation, we speculate that the combined analysis of salivary aldosterone (SA) and salivary cortisol (SC) might improve discrimination between normals and Conn's patients (CP). Thus, we analyzed concentrations of SA by our in-house assay and SC by a commercial assay in order to determine the ratio between the two hormones. 14 subjects with confirmed Conn's and 17 healthy volunteers (HV) participated in the study. Daytime saliva samples were collected by Salivettes (Sarstedt, Nümbrecht) between 7am and 11am. Furthermore, in a subgroup (12 CP, 8 HV) an ACTH stimulation test was performed to investigate the influence of pituitary stimulation on the ratio. Un-stimulated SA was 112.7±58.7pg/ml in CP and 65.0±24.4 in HV. The aldosterone to cortisol ratio (ACR) (±SD) was 0.107±0.087 in CP compared to 0.065±0.065 in HV (p<0.001). Post-ACTH stimulation test however, ACR decreased in both groups, 0.014±0.010 and 0.014±0.013 respectively, due to the greatly increased levels of SC compared to the less pronounced increase in SA. This influence of the pituitary ACTH stimulus also can affect the ratio throughout the day. Preliminary data in 8 CP showed that the ACR is higher in the evening compared to daytime due to lower variation in aldosterone values together with decreasing cortisol. 8am values yielded 0.055±0.034 compared to a 0.423±0.565 12pm ACR. So far, our data has shown that at baseline a ratio higher than 0.1 is suggestive of Conn's syndrome. We propose the possibility of using this ratio, elevated in CP compared to controls, as a tool in the diagnosis of primary aldosteronism.