Benny So

Adrenal vein sampling may not be a gold-standard diagnostic test in primary aldosteronism: final diagnosis depends upon which interpretation rule is used

BackgroundAdrenal vein sampling (AVS) is considered the gold-standard test to demonstrate unilateral aldosterone excess in primary aldosteronism, yet no single approach to interpretation of AVS has been externally validated.HypothesisThere may be significant inter-observer variability in the final diagnosis of unilateral vs. bilateral aldosterone excess depending on which AVS interpretation rule is used.MethodsRetrospective chart review of 63 subjects with primary aldosteronism undergoing AVS and 40 subsequent adrenalectomies for presumed unilateral aldosteronism. The data from the AVS were retrospectively re-analyzed according to a variety of interpretation criteria published in the literature. Using 40 subjects undergoing surgery, pathology and clinical outcomes defined the final diagnosis of aldosteronism subtype, and these subjects’ AVS results were used to estimate the true sensitivity and specificity of the various approaches to AVS interpretation.ResultsDiagnostic discrepancies exist between the different AVS interpretation rules. Successful adrenal vein catheterization was confirmed in between 13% and 77% of AVS attempts. Sensitivity of AVS ranged from 47% to 100% and specificity 55–100%. Only 17% of all cases would be categorized uniformly by all interpretation criteria. Use of biochemical catheter placement criteria and ACTH infusion improved the proportions of AVS results defined as successful and showing lateralization.ConclusionsWe found substantial variabilty in final diagnosis by using different systems of interpreting AVS results as suggested in the literature This suggests AVS may not always be considered a gold-standard diagnostic test.

High-Probability Features of Primary Aldosteronism May Obviate the Need for Confirmatory Testing Without Increasing False-Positive Diagnoses

This retrospective review examined all primary aldosteronism (PA) adrenal vein sampling (AVS), diagnoses, and outcomes from an endocrine hypertension unit where confirmatory testing was abandoned in 2005 to determine the potential rate of false‐positive diagnoses. Patients with outcome‐verified PA (surgical patients) were compared with patients with high‐probability PA (nonsurgical but high aldosterone‐renin ratio, imaging abnormalities, and/or hypokalemia) or possible PA (nonsurgical, no features besides mild elevation of aldosterone‐renin ratio, a potential false diagnosis of PA). Of 83 patients, 58% had unilateral PA and 42% had bilateral aldosteronism. Less than 3% of the cohort showed bilateral aldosteronism without hypokalemia or computed tomographic findings, potentially representing the false‐positive PA diagnosis rate with omission of confirmatory tests in this population. In a hypertension referral unit enriched in high‐probability PA cases and where high AVS success is achieved, omission of a PA confirmatory test yields a high rate of surgical diagnosis with few potential false‐positive diagnoses.

Catheterization during adrenal vein sampling for primary aldosteronism: failure to use (1-24) ACTH may increase apparent failure rate.

“Successful” adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non‐use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH‐S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH‐S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH‐S samples, 94% of right‐sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right‐ and 44% of left‐sided samples met the 3:1 cortisol criteria. However, 95% of apparent “failed” baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non–ACTH‐stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH‐stimulated sampling is the preferred means to confirm catheterization during AVS.

Unadjusted Plasma Renin Activity as a “First-Look” Test to Decide Upon Further Investigations for Primary Aldosteronism

The authors sought to define the 95th percentile of plasma renin activity (PRA) in a sample of patients with confirmed primary aldosteronism (PA) prior to adjustment of medications as a practical “first‐look” test to identify those with very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR) was measured without adjustment of antihypertensive medications, with further workup as appropriate. Two groups were defined: patients with surgically “confirmed PA” (n=58) and patients with “high‐probability PA” (n=59), defined as having any of the following: computed tomography–confirmed adrenal adenoma plus lateralizing adrenal vein sampling (AVS) without surgery, high ARR and hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia and two had adrenal adenomas. There was no difference between the confirmed and high probability groups. In the absence of highly suspicious clinical features, patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation for PA.