Clinical prediction model for primary aldosteronism subtyping and special focus on adrenal volumetric assessment.

PURPOSE: Our aim was to develop a prediction model based on a simple score with clinical, laboratory, and imaging findings for the subtype diagnosis of primary aldosteronism (PA). The contribution of adrenal volumetric assessment to PA subtyping was also investigated. METHODS: Thirty-five patients with adequate cannulation in adrenal venous sampling (AVS) were included. Laboratory data, the saline infusion test (SIT), and the AVS results of patients with PA were retrospectively evaluated. Volumetric assessment was performed using magnetic resonance imaging (MRI) and the ratio of adrenal volumes was calculated after adjusting for gender- and side-specific mean reference values of both adrenal glands. RESULTS: The AVS was consistent with unilateral PA in 49% and bilateral in 51% of the patients. Hypertension as a reason for work-up, the highest aldosterone/lowest potassium value higher than 12, the percentage of plasma aldosterone concentration (PAC) reduction after SIT by equal or less than 43.5%, the use of oral potassium replacement, unilateral disease at pre-AVS imaging, and a ratio of adjusted adrenal volumes equal to or below 1.7 were indicative of unilateral disease in univariate logistic regression analysis concerning the distinction of PA subtyping (p < 0.05). Multivariate logistic regression analysis also revealed that adrenal volumetric assessment has an impact on PA subtyping (p < 0.05). In the prediction model, when each of the six parameters that were significant in the univariate logistic regression analysis was assigned one point, < 4 predicted bilateral PA, whereas ≥ 4 predicted unilateral PA (AUC:0.92, p < 0.001). CONCLUSION: This prediction model before AVS may serve as a convenient and practical approach, while an adjusted adrenal volumetric assessment can make a positive contribution to PA subtyping.

Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization.

CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).

Adrenal vein sampling for primary aldosteronism: the assessment of selectivity and lateralization of aldosterone excess baseline and after adrenocorticotropic hormone (ACTH) stimulation.

BACKGROUND: Adrenal vein sampling is crucial for identifying the primary aldosteronism subtypes, but the cutoff values for ascertaining selectivity of catheterization and lateralization of aldosterone secretion remain controversial. OBJECTIVES: To investigate the safety of adrenal vein sampling, the cutoff values for the selectivity and lateralization indexes, and the effect of adrenocorticotropic hormone stimulation on selectivity index and lateralization index performance. DESIGN: We assessed the proportion of selective adrenal vein sampling at different selectivity index cutoff values in 151 consecutive patients with primary aldosteronism undergoing bilaterally simultaneous adrenal vein sampling. Aldosterone-producing adenoma was diagnosed on the basis of the evidence of primary aldosteronism and lateralized aldosterone secretion, adenoma at pathological examination, and normokalemia, and correction of primary aldosteronism and cure or improvement of hypertension at follow-up. In 44 patients with bilaterally selective adrenal vein sampling and unequivocal diagnosis of aldosterone-producing adenoma on the basis of all these criteria, we examined the cutoff values of the lateralization index for assessing the lateralization of aldosterone excess and the effect of adrenocorticotropic hormone stimulation on selectivity index and lateralization index. RESULTS: Adrenal vein rupture occurred in one case (0.7%). Bilaterally selective adrenal vein sampling decreased steadily (from 79.9 to 40.2%) with increase in the selectivity index cutoffs from 1.1 to 5.0. Likewise, the proportion of correctly identified aldosterone-producing adenomas decreased (from 95.5 to 43.2%) with increase in lateralization index cutoffs from 1.125 to 5.0. Adrenocorticotropic hormone improved the assessment of selectivity but exerted a confounding effect on lateralization index. CONCLUSION: Adrenal vein sampling is safe; increasing the selectivity index cutoffs lowers the number of usable adrenal vein samplings; higher lateralization index cutoff values lead to missing a proportion of aldosterone-producing adenomas. The improved selectivity rate provided by adrenocorticotropic hormone stimulation should be weighed against the loss of correct lateralization.

Dopaminergic regulation of aldosterone secretion: assessment in different subtypes of primary aldosteronism and in essential hypertension.

The inhibitory effect of dopamine on aldosterone secretion was investigated in patients with different types of primary aldosteronism, six with idiopathic hyperaldosteronism (IHA) and four with dexamethasone-suppressible hyperaldosteronism (DSH), and in 10 patients with essential hypertension. The effects of 10 mg metoclopramide given intravenously, 10 mg bromocriptine given orally and 100 micrograms adrenocorticotrophic hormone given intravenously on plasma aldosterone and renin activities were investigated in all patients. Metoclopramide induced a rise in plasma aldosterone activity only in patients with IHA and not in those with DSH and essential hypertension. After bromocriptine plasma aldosterone concentrations decreased in patients with IHA only, and after adrenocorticotrophic hormone plasma aldosterone concentrations increased in patients with DSH only. Plasma renin activity was unaffected in all cases. These results provide evidence of increased endogenous dopaminergic inhibition of aldosterone secretion in IHA and of a blunted aldosterone response in both DSH and essential hypertension.