Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas

Abstract

Objective: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6%-16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone SIT (DSIT) by applying both tests on the same subjects. Methods: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls, with normal adrenal imaging. Serum cortisol, aldosterone and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean+2SD values from the controls, we defined the upper normal limits (UNL) for cortisol, aldosterone and PRC for both the SIT and DSIT. Results: In the controls, the post-DSIT aldosterone levels and the ARR were approximately 2-fold and 3-fold lower respectively than the corresponding post-SIT values (all p=0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion. Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. Conclusions: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk for developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant autonomous cortisol secretion.

Autonomous Aldosterone Secretion in Patients with Adrenal Incidentaloma

“…Piaditis et al reported a 24.1% prevalence of 'subtle AAS' among patients with a single adrenal adenoma in a case-control study, in which Ald and DRC cutoffs were established for a DXM-enhanced saline infusion test based on data obtained from controls with NT and normal adrenal glands [16]. A similar (29.4%) biochemically overt PA prevalence was obtained with the same approach by these researchers recently, and, crucially, MRA and adrenalectomy were highly effective in the therapy of HT among PA patients [17]. While our approach of using merely a permissive ADRR to diagnose AAS is perhaps overly simplistic, an assessment of the congruity between these would be valuable (the mean basal ADRR of adrenal adenoma patients was ca.…”

High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension

“…In these studies, the diagnosis of PA was based on the standard methodology initially using as a screening test the basal PAC/PRA ratio and as confirmatory test mainly the 2 lt saline infusion. This choice significantly reduces the sensitivity of these diagnostic tests because they aim to suppress only the renin-angiotensin II-system, leaving the secretion of ACTH unaffected [ 17 ].…”

“…To define the normal response of ALD and ARR to the ultra-low ACTH test, 23 normotensive individuals with normal adrenals examined by CT or magnetic resonance imaging (MRI) were recruited and served as controls. Normotensive PA was excluded using the D-SIT (dexamethasone-saline infusion test) diagnostic method [ 17 ]. We preferred the use of D-SIT instead of FDST because it was easier to use and, therefore, better acceptable by the NC group.…”

Primary Aldosteronism Prevalence – An Unfolding Story

“…It has been suggested that biochemically overt PA is not a rare entity in patients with adrenal incidentaloma and normal blood pressure. [77,78] Kmieć and colleagues conducted a prospective study attempting to detect subclinical autonomous aldosterone secretion in patients with adrenal incidentaloma by using permissive criteria of ARR >1.2 (ng/dL)/(mIU/L) (approximately 10 (ng/dL)/(ng/mL/hour)) and plasma aldosterone concentration >4 ng/dL. Normotensive patients with urine aldosterone excretion >10 µg/day were considered to have mild autonomous aldosterone secretion, while hypertensive patients with urine aldosterone >12 µg/day were diagnosed with overt PA.…”

“…An unresolved question regarding the evaluation of adrenal incidentaloma is whether we should screen for autonomous aldosterone production in patients who do not have hypertension. It has been suggested that biochemically overt PA is not rare in patients with adrenal incidentaloma and normal blood pressure [77,78]. Kmieć and colleagues conducted a prospective study attempting to detect subclinical autonomous aldosterone secretion in patients with adrenal incidentaloma by using permissive criteria of ARR > 1.2 (ng/dL)/(mIU/L) (approximately 10 (ng/dL)/(ng/mL/h)) and plasma aldosterone concentration > 4 ng/dL.…”