External Validation of Clinical Prediction Models in Unilateral Primary Aldosteronism.

BACKGROUND: Targeted treatment of primary aldosteronism (PA) is informed by adrenal vein sampling (AVS), which remains limited to specialized centers. Clinical prediction models have been developed to help select patients who would most likely benefit from AVS. Our aim was to assess the performance of these models for PA subtyping. METHODS: This external validation study evaluated consecutive patients referred for PA who underwent AVS at a tertiary care referral center in Alberta, Canada during 2006-2018. In alignment with the original study designs and intended uses of the clinical prediction models, the primary outcome was the presence of lateralization on AVS. Model discrimination was evaluated using the C-statistic. Model calibration was assessed by comparing the observed vs. predicted probability of lateralization in the external validation cohort. RESULTS: The validation cohort included 342 PA patients who underwent AVS (mean age, 52.1 years [SD, 11.5]; 201 [58.8%] male; 186 [54.4%] with lateralization). Six published models were assessed. All models demonstrated low-to-moderate discrimination in the validation set (C-statistics; range, 0.60-0.72), representing a marked decrease compared with the derivation sets (range, 0.80-0.87). Comparison of observed and predicted probabilities of unilateral PA revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.35-1.67), signifying systematic underprediction of lateralizing disease. Calibration slopes were consistently <1 (range, 0.35-0.87), indicating poor performance at the extremes of risk. CONCLUSIONS: Overall, clinical prediction models did not accurately predict AVS lateralization in this large cohort. These models cannot be reliably used to inform the decision to pursue AVS for most patients.

Apparent failed and discordant adrenal vein sampling: A potential confounding role of cortisol cosecretion?

OBJECTIVE: Adrenal vein sampling (AVS) and computed tomography (CT) often show confusingly discordant lateralisation results in primary aldosteronism (PA). We tested a biochemical algorithm using AVS data to detect cortisol cosecretion as a potential explanation for discordant cases. DESIGN: Retrospective analysis from a large PA + AVS database. PATIENTS: All patients with PA and AVS, 2005-2020. MEASUREMENTS: An algorithm using biochemical data from paired AVS + CT images was devised from physiological first principles and informed by data from unilateral, AVS-CT concordant patients. The algorithm involved calculations based upon the expectation that low cortisol levels exist in adrenal vein effluent opposite an aldosterone-and-cortisol-producing adrenal mass and may reverse lateralisation due to inflated aldosterone/cortisol ratios. MAIN OUTCOMES: The algorithm was applied to cases with discordant CT-AVS lateralisation to determine whether this might be a common or explanatory finding. Clinical and biochemical characteristics of identified cases were collected via chart review and compared to CT-AVS concordant cases to detect evidence of biological plausibility for cortisol cosecretion. RESULTS: From a total of 588 AVS cases, 141 AVS + CT pairs were clear unilateral PA cases, used to develop the three-step algorithm for AVS interpretation. Applied to 88 AVS + CT discordant pairs, the algorithm suggested possible cortisol cosecretion in 40%. Case review showed that the proposed cortisol cosecretors, as identified by the algorithm, had low/suppressed adrenocorticotropic hormone levels, larger average nodule size and lower plasma aldosterone. CONCLUSIONS: Pending external validation and outcome verification by surgery and tissue immunohistochemistry, cortisol cosecretion from aldosteronomas may be a common explanation for discordant CT-AVS results in PA.

Outcomes of a Specialized Clinic on Rates of Investigation and Treatment of Primary Aldosteronism.

Importance: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated. Objective: To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors. Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension. Main Outcomes and Measures: We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics. Results: Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program. Conclusions and Relevance: In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.

Surgical Outcomes Among Primary Aldosteronism Patients Without Visible Adrenal Lesions.

CONTEXT: Many patients with unilateral primary aldosteronism (PA) have normal adrenal imaging, but little is known about their outcome following adrenalectomy. OBJECTIVE: To evaluate biochemical and clinical outcomes after adrenalectomy in patients with unilateral PA and normal-appearing adrenal imaging. DESIGN: Retrospective cohort study of patients seen between January 2006 and May 2018. SETTING: A Canadian tertiary care PA referral center. PATIENTS: Consecutive individuals with PA, normal cross-sectional adrenal imaging, and lateralizing adrenal vein sampling (AVS) who underwent adrenalectomy during the study period. PRIMARY OUTCOME: Biochemical response to adrenalectomy graded according to the Primary Aldosteronism Surgical Outcome criteria. RESULTS: A total of 40 patients were included. Biochemical outcomes were available for 33 people (mean age, 54.7 years; 91% male; median follow-up, 2.7 months), with 28 (85%) showing a complete or partial response and 5 (15%) with no response. Clinical outcomes were available for 36 people (mean age, 54.6 years; 86% male; median follow-up, 9.8 months), with 31 (86%) demonstrating a complete or partial response and 5 (14%) with no response. CONCLUSIONS: The prognosis after adrenalectomy is highly favorable for patients with unilateral PA and normal-appearing adrenal imaging. Patients with lateralizing disease should be considered for surgery despite apparently normal adrenal imaging.

Unilateral Disease Is Common in Patients With Primary Aldosteronism Without Adrenal Nodules.

BACKGROUND: Patients with primary aldosteronism (PA) without apparent adrenal nodularity have not been well characterised in the literature. The aim of this study was to assess for unilateral aldosterone hypersecretion among patients with primary aldosteronism with normal-appearing adrenals using adrenal vein sampling (AVS). METHODS: In this cross-sectional study performed at a Canadian tertiary care centre, we reviewed all consecutive PA patients lacking a definitive adrenal nodule who were referred for AVS in the work-up of PA between January 2006 and May 2018. AVS indications included an elevated aldosterone-to-renin ratio and high-probability features of PA. RESULTS: In total, 174 patients were included (mean age, 52.0 years; 62.6% male), and 70 (40.2%) had unilateral aldosterone hypersecretion. There was a positive linear association between higher age categories (by decade) and lateralisation (P = 0.03). For every decade of age, there was a 30% higher odds of lateralisation (odds ratio, 1.03 per year; 95% confidence interval, 1.00-1.05). The frequency of lateralisation was higher in males compared with females (47.7% vs 27.7%), with a 2-fold greater odds of unilateral disease (odds ratio, 2.38; 95% confidence interval, 1.23-4.61). Traditional biomarkers of lateralisation among patients with adrenal nodules (eg, serum potassium and aldosterone-to-renin ratio levels) were not predictive of lateralisation in this population. CONCLUSIONS: Many patients with PA who lack definitive adrenal nodules have lateralising disease. Efforts to optimise referrals for AVS may be prioritised by focusing on patients most likely to have unilateral disease, especially males and older adults.

Repeat Adrenal Vein Sampling in Aldosteronism: Reproducibility and Interpretation of Persistently Discordant Results.

CONTEXT: The reproducibility of adrenal vein sampling (AVS) is unknown. OBJECTIVE: This work aimed to determine reproducibility of biochemical results and diagnostic lateralization in patients undergoing repeat AVS. METHODS: A retrospective chart review was conducted of single-center, single-operator AVS procedures at a tertiary care center. Included were patients with confirmed primary aldosteronism (PA) undergoing repeat AVS because of concerns about technical success or discordant diagnostic results. Simultaneous AVS was performed by an experienced operator using a consistent protocol of precosyntropin and postcosyntropin infusion. Among successfully catheterized adrenal veins (selectivity index ≥ 2), the correlation of the adrenalaldosterone/cortisol (A/C) ratio was measured between the first and second AVS. The secondary outcome measure was diagnostic agreement on repeat AVS lateralization (lateralization index ≥ 3). RESULTS: There were 46 sets of AVS from 23 patients at a median of 3 months apart. There was moderate correlation in A/C ratios in the adrenal veins and inferior vena cava (Spearman r = 0.49-0.59, P < .05) pre cosyntropin. Post cosyntropin, the correlation was better (Spearman r = 0.67-0.76, P < .05). In technically successful AVS, there was moderate correlation between the repeated lateralization indices (Spearman r = 0.53, P < .05). In 15 patients in whom repeat AVS was performed because of apparent lateralization discordance with computed tomography imaging, the final diagnosis was the same in the second AVS procedure. Initial failed AVS was successful 75% of the time on repeat attempt. CONCLUSION: Repeat AVS was feasible and usually successful when an initial attempt failed. There was modest correlation between individual repeat adrenal A/C ratios and lateralization indices when AVS was performed twice. The final lateralization diagnosis was identical in all cases. This demonstrates that AVS is a reliable and reproducible localizing test in PA.

Basal contralateral aldosterone suppression is rare in lateralized primary aldosteronism.

CONTEXT: Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes. OBJECTIVES: To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure. METHODS: In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. RESULTS: Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure. CONCLUSIONS: In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.

Adrenal vein sampling: External validation of multinomial regression modelling and left adrenal vein-to-peripheral vein ratio to predict lateralization index without right adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) failure is mainly due to right adrenal vein unavailability. Multinomial regression modelling (MRM) and left adrenal vein-to-peripheral vein ratio (LAV/PV) were proposed to predict the lateralization index without the right AVS. OBJECTIVE: To assess external validity of MRM and LAV/PV to predict lateralization index when right adrenal vein sampling is missing. DESIGN: Diagnostic retrospective study. PATIENTS: Development and validation cohorts included AVS of 174 and 122 patients, respectively, from 2 different centres. MEASUREMENTS: Development and validation cohort data were used, respectively, for calibration and for validation of MRM and LAV/PV to predict the lateralization index without the right adrenal vein sampling. Sensitivity and specificity of MRM and LAV/PV were compared between both centres at different pre-established specificity thresholds based on receiver operating characteristic curves generated from the development cohort data. RESULTS: At a specificity threshold of 95% set in the development cohort, specificity values exceeded 90% (range, 90.6%-98.8%) for all verified MRM and LAV/PV models in the validation cohort. Corresponding sensitivities for MRM and LAV/PV, respectively, range from 54.1% to 83.7% and 32.8% to 88.4% for the development cohort compared to 33.3%-87.5% and 2.8%-79.2% for the validation cohort. Overall, diagnostic accuracy of both methods was higher to detect right (82.8%-93.5%) than left (70.2%-80.6%) lateralization index status in both centres. CONCLUSIONS: Minimal changes in specificity from development to validation cohorts validate the use of MRM and LAV/PV to predict the lateralization index when the right AVS is missing. Both methods had better accuracy for right than left lateralization detection.

Surprisingly low aldosterone levels in peripheral veins following intravenous sedation during adrenal vein sampling: implications for the concept of nonsuppressibility in primary aldosteronism.

BACKGROUND: Constituitively high and nonsuppressible aldosterone levels are considered to be the hallmark of primary aldosteronism. We observed a high proportion of primary aldosteronism patients with surprisingly low aldosterone levels in peripheral veins during adrenal vein sampling (AVS) and sought to further characterize the phenomenon. METHODS: Database analysis of patients with primary aldosteronism at the University of Calgary who underwent AVS under intravenous sedation. Aldosterone levels following sedation were compared with aldosterone measured at diagnosis in the free-living state. A validation analysis was performed on a similar database from the University of British Columbia. RESULTS: Seventy-two percent of 127 patients had AVS aldosterone levels more than 30% lower than their outpatient aldosterone measure (468 vs. 278 pmol/l, P < 0.001). Thirty-nine percent of patients had aldosterone levels less than 200 pmol/l and 13% had levels less than 140 pmol/l during AVS. Repeat analysis on the UBC cohort produced similar results with 88% having an aldosterone more than 30% lower than the outpatient measure (median aldosterone 568 vs. 201 pmol/l, P < 0.001). CONCLUSION: A majority of primary aldosteronism patients have markedly lower aldosterone levels during sedated AVS compared with those found during outpatient diagnosis. In the absence of confounding medications, hypokalemia, circadian timing, postural variation and with low correlation to measures of hypothalamic-pituitary-adrenal activity, this suggests that many primary aldosteronism patients may, at times, have aldosterone levels that are surprisingly low-normal. This finding challenges the concept that a persistently high and nonsuppressible aldosterone level is a sine qua non of primary aldosteronism.

Discordance Between Imaging and Adrenal Vein Sampling in Primary Aldosteronism Irrespective of Interpretation Criteria.

BACKGROUND: Subtyping of primary aldosteronism (PA) using imaging and adrenal vein sampling (AVS) may yield discordant results, causing confusion in management. Interpretation criteria for AVS lateralization may affect discordance rates. METHODS: We identified consecutive patients with PA who underwent AVS at a quaternary care center between January 2006 and May 2018. Patient demographics, laboratory results, diagnostic imaging, and AVS results were retrieved. Adrenal cross-sectional imaging was compared with AVS findings. The presence of lateralization was defined using varying thresholds for the lateralization index (LI) from >2:1 to >5:1. Discordance was defined by a unilateral lesion on imaging with contralateral or nonlateralization on AVS. RESULTS: A total of 342 patients were included; 68.7% had hypokalemia. With cross-sectional imaging, 191 (55.6%) patients had unilateral lesions, 47 (13.7%) had bilateral lesions, and 104 (30.4%) had normal imaging. Overall discordance rates were high, ranging from 22% to 28% for LI thresholds of >2:1 and >5:1, respectively. Discordance between imaging and AVS was positively correlated with LI threshold stringency (P < 0.001). Patients with normal or bilateral lesions on imaging frequently lateralized on AVS. Lateralization, when present, was approximately equal between left and right sides, irrespective of the LI threshold. CONCLUSIONS: Discrepancies between imaging and AVS were common, even among patients with nonspecific imaging. Discordance was greatest with the strictest AVS interpretation criteria. Even under the most lenient thresholds, apparent discordance between imaging and AVS exceeded 20% and may limit the ability to make surgical decisions. Reliance on imaging alone for detecting lateralization may be misleading.

Application of strict criteria in adrenal venous sampling increases the proportion of missed patients with unilateral disease who benefit from surgery for primary aldosteronism.

OBJECTIVES: Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed. METHODS: Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated. RESULTS: Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization. CONCLUSION: Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.

A Multi-institutional Comparison of Adrenal Venous Sampling in Patients with Primary Aldosteronism: Caution Advised if Successful Bilateral Adrenal Vein Sampling is Not Achieved.

INTRODUCTION: In patients with primary aldosteronism (PA), adrenal venous sampling (AVS) is recommended to differentiate between unilateral (UNI) or bilateral (BIL) adrenal disease. A recent study suggested that lateralization could be predicted, based on the ratio of aldosterone/cortisol levels (A/C) between the left adrenal vein (LAV) and inferior vena cava (IVC), with a 100% positive predictive value (PPV). This study aimed to validate those findings utilizing a larger, multi-institutional cohort. METHODS: A retrospective review was performed of patients with PA who underwent AVS from 2 tertiary-care institutions. Laterality was predicted by an A/C ratio of >3:1 between the dominant and non-dominant adrenal. AVS results were compared to LAV/IVC ratios utilizing the published criteria (Lt ≥ 5.5; Rt ≤ 0.5). RESULTS: Of 222 patients, 124 (57%) had UNI and 98 (43%) had BIL disease based on AVS. AVS and LAV/IVC findings were concordant for laterality in 141 (64%) patients (69 UNI, 72 BIL). Using only the LAV/IVC ratio, 54 (24%) patients with UNI disease on AVS who underwent successful surgery would have been assumed to have BAH unless AVS was repeated, and 24 (11%) patients with BIL disease on AVS may have been incorrectly offered surgery (PPV 70%). Based on median LAV/IVC ratios (left 5.26; right 0.31; BIL 2.84), no LAV/IVC ratio accurately predicted laterality. DISCUSSION: This multi-institutional study of patients with both UNI and BIL PA failed to validate the previously reported PPV of LAV/IVC ratio for lateralization. Caution should be used in interpreting incomplete AVS data to differentiate between UNI versus BIL disease and strong consideration given to repeat AVS prior to adrenalectomy.

Plasmocytoma presented as pancreatic head mass.

Multiple myeloma is a malignant tumour characterized by proliferation of a single clone of plasma cells, this cell line will produce large amount of ineffective immunoglobulins that are ineffective at fighting infection resulting in immunosuppression. These are medullary tumours most of the time; however, in rare cases they may arise extra medullary. The incidence of extramedullary plasmocytoma is about 5% and they arise in the chest most of the time; but they can also arise in other body systems like gastrointestinal system, which is involved in 10% of the time. We present a very rare case of primary plasmocytoma involving the pancreas. According to our research, there are only 25 cases of primary pancreatic plasmocytoma reported in english literature.

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.

A clinical prediction score for diagnosing unilateral primary aldosteronism may not be generalizable.

BACKGROUND: A published clinical prediction score indicated that a unilateral adrenal adenoma and either hypokalemia or an estimated glomerular filtration rate of 100 ml/min/1.73 m2 was 100% specific for unilateral primary aldosteronism. This study aimed to validate this score in a separate cohort of patients with primary aldosteronism. METHODS: A review of patients with primary aldosteronism from June 2005 to July 2013 at a single center's hypertension clinic. One hundred twelve patients with primary aldosteronism underwent successful adrenal vein sampling and the 110 patients with full data available were included in the final analysis. Adrenal vein sampling was performed all patients desiring surgery by the simultaneous collection of sample prior to and 15 minutes after a cosyntropin infusion with a 3:1 aldosterone/cortisol ratio diagnosing unilateral primary aldosteronism. The derived score was applied to the cohort. Sensitivity and specificity were calculated for clinical prediction score of ≥5 points. RESULTS: There were 64 patients found to have unilateral primary aldosteronism and 48 had bilateral disease. A score ≥5 points had 64% sensitivity (95% confidence interval, 51-76) and 85% specificity (95% confidence interval, 71-94) for unilateral disease. Four patients had lateralization of primary aldosteronism to the side contralateral to the adenoma. CONCLUSIONS: The 100% specificity of the score for the unilateral origin of primary aldosteronism was not validated in this cohort with a score of ≥5 points. At best, a high score in this prediction rule may be an additional tool for helping to confirm a decision to offer patients adrenal vein sampling.

Intraprostatic hematoma with active bleeding post-prostate biopsy.

To the best of our knowledge, we report the first known case of a large intraprostatic hematoma with active bleeding following transrectal ultrasound-guided prostate biopsy.

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.

Modification of the protocol for selective adrenal venous sampling results in both a significant increase in the accuracy and necessity of the procedure in the management of patients with primary hyperaldosteronism.

BACKGROUND: Adrenal venous sampling (AVS) is used in the work-up of primary hyperaldosteronism (PA) to distinguish unilateral PA from bilateral adrenal hyperplasia. In 2006, we reported that only 44% of AVS had biochemical evidence of bilateral adrenal vein cannulation (BAVC). Critical appraisal of our practice resulted in a protocol change. This study examined the impact of this new protocol on both the technical success rate and its influence on management of PA. METHODS: Since 2006, all patients with biochemically documented PA referred to either a single endocrine surgeon or endocrine specialist underwent AVS. Successful BAVC was defined as an adrenal vein to inferior vena cava/cortisol ratio of >3:1. Lateralization was defined as an aldosterone:cortisol ratio >3 times the unaffected side. RESULTS: Of the 86 AVS performed on 84 patients with PA, 82 had BAVC (95%). AVS altered the management in 26 of 84 (31%) patients. Despite clear unilateral findings on imaging in 45 patients, AVS demonstrated bilateral adrenal hyperplasia. in 10 and contralateral disease in 3. AVS confirmed unilateral PA in 5 patients with equivocal <1 cm nodules. In 4 of 25 patients with normal adrenal glands, AVS demonstrated lateralization. AVS demonstrated unilateral PA in 4 of 9 patients in whom imaging suggested bilateral adrenal hyperplasia. CONCLUSION: Our new AVS protocol resulted in a marked improvement in BAVC. AVS influenced management in a third of patients with PA. Surgical decision-making cannot be made solely on the basis of cross-sectional imaging.