Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Antecubital vein combined with femoral vein pathway could shorten the learning curve of simultaneous bilateral adrenal vein sampling.

During our previous bilateral adrenal vein sampling (AVS) procedure, the authors observed that accessing the left adrenal vein through the antecubital vein was more feasible than the conventional femoral vein. Meanwhile, the femoral vein pathway facilitated access to the right adrenal vein than the antecubital vein pathway. Therefore, the authors hypothesized that simultaneous bilateral AVS via the antecubital combined with the femoral vein pathway could improve the success rate. A total of 94 cases of AVS via the antecubital combined with the femoral vein pathway were performed, while the remaining 20 cases employed the antecubital vein pathway at our center between August 2020 and April 2023. Furthermore, a meta-analysis was conducted in this study using 15 selected articles to determine the success rate of AVS in each center and pathway. The success rate of ACTH-stimulated simultaneous bilateral AVS via the antecubital vein combined with the femoral vein pathway was 92.85% (P = .503) on the right and 95.00% (P < .001) on the left. In the antecubital vein pathway, the success rates were only 25.00% (P < .001) on the right side and 80.00% (P = .289) on the left side. The results of meta-analysis demonstrated a success rate of 78.16% on the right and 94.98% on the left for ACTH-stimulated AVS via the femoral vein pathway. Based on our center's experience, simultaneous bilateral adrenal vein sampling via the combined pathway could improve the success rate of AVS in the short term and shorten the learning curve.

Surgical versus medical management of patients with primary hyperaldosteronism and indeterminate adrenal vein sampling: A 10-year experience of the Cleveland Clinic.

In patients with primary hyperaldosteronism (PA), adrenal vein sampling (AVS) can identify patients suitable for unilateral adrenalectomy. However, in AVS with an indeterminate aldosterone-to-cortisol lateralization (ACL) ratio of 3.0-4.0, clinical guidance is unclear. The authors screened all patients undergoing AVS at the Cleveland Clinic from October 2010 to January 2021 and identified 18 patients with indeterminate ACL results. Ten underwent adrenalectomy and eight continued medical management. The surgical group was younger (58.5 vs. 68 years, p = .17), and more likely to have a unilateral imaging adrenal abnormality (90% vs. 38%, p = .043) and a lower contralateral suppression index (0.63 vs. 1.1, p = .14). Post-treatment, the surgical group had a significant reduction in diastolic blood pressure (-5.5 mmHg, p = .043) and aldosterone (4.40 vs. 35.80 ng/mL, p = .035) and required fewer anti-hypertensive medications (2 vs. 3, p = .015). These findings may support the benefit of adrenalectomy in a select group of patients with indeterminate ACL.

Clinical characteristics and outcomes of adrenal hemorrhage.

BACKGROUND: Although uncommon, adrenal hemorrhage has multiple etiologies. Because clinical characteristics, management, and outcomes of patients with adrenal hemorrhage are inadequately described, we examined the underlying etiology, need for intervention, evolution of imaging characteristics, and adequacy of subsequent evaluation. METHODS: We performed a retrospective review of patients diagnosed with adrenal hemorrhage (radiologist-confirmed density consistent with hemorrhage on computed tomography) from 2005 to 2021 at a university-based institution. Demographic characteristics, hemorrhage etiology, and subsequent follow-up were analyzed. RESULTS: Of 193 adrenal hemorrhage patients, the mean age was 49.2 ± 18.3 years, and 35% were female. Clinical presentations included trauma (47%), abdominal or flank pain (28%), incidental findings on imaging acquired for other reasons (12%), postoperative complication (8%), or shock (3%). Hemorrhage outside of the gland was present in 62% of patients. Unilateral hemorrhage was more frequent (93%) than bilateral (7%). A total of 12% of patients had nodules, but only 70% of these were identified on initial imaging, and only 43% had hormonal evaluation. Of 7 patients who had adrenalectomy or biopsy, pathology was either benign (57%) or nonadrenal malignancy (43%). No adrenocortical carcinomas were identified. Follow-up imaging was performed in 56% of patients and revealed decreased, stable, resolved, or increased adrenal hemorrhage size in 39%, 19%, 30%, and 12% of patients, respectively. CONCLUSION: Adrenal hemorrhage is secondary to multiple etiologies, most commonly trauma. In the setting of adrenal hemorrhage, many adrenal nodules were not identified on initial imaging. Only a minority of patients with nodules underwent "complete" biochemical evaluation. Follow-up imaging may improve the identification of underlying nodules needing hormonal evaluation.

Adrenal Vein Sampling: Tips and Tricks.

Adrenal vein sampling (AVS) is the standard method for distinguishing unilateral from bilateral sources of autonomous aldosterone production in patients with primary aldosteronism. This procedure has been performed at limited specialized centers due to its technical complexity. With recent advances in imaging technology and knowledge of adrenal vein anatomy in parallel with the development of adjunctive techniques, AVS has become easier to perform, even at nonspecialized centers. Although rare, anatomic variants of the adrenal veins can cause sampling failure or misinterpretation of the sampling results. The inferior accessory hepatic vein and the inferior emissary vein are useful anatomic landmarks for right adrenal vein cannulation, which is the most difficult and crucial step in AVS. Meticulous assessment of adrenal vein anatomy on multidetector CT images and the use of a catheter suitable for the anatomy are crucial for adrenal vein cannulation. Adjunctive techniques such as intraprocedural cortisol assay, cone-beam CT, and coaxial guidewire-catheter techniques are useful tools to confirm right adrenal vein cannulation or to troubleshoot difficult blood sampling. Interventional radiologists should be involved in interpreting the sampling results because technical factors may affect the results. In rare instances, bilateral adrenal suppression, in which aldosterone-to-cortisol ratios of both adrenal glands are lower than that of the inferior vena cava, can be encountered. Repeat sampling may be necessary in this situation. Collaboration with endocrinology and laboratory medicine services is of great importance to optimize the quality of the samples and for smooth and successful operation. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Portal venous contrast enhancement ratio of the adrenal glands and spleen as prognostic marker of mortality in patients with acute mesenteric ischemia.

PURPOSE: Contrast enhancement of the adrenal gland defined by computed tomography (CT) was previously analyzed as a prognostic factor for critically ill patients in various diseases. However, no study investigated this quantitative parameter in patients with acute mesenteric ischemia. Therefore, the aim of this study was to evaluate the prognostic value of the contrast enhancement of the adrenal glands in patients with clinically suspected AMI. METHODS: All patients with clinically suspected AMI were retrospectively assessed between 2016 and 2020. All patients underwent surgical exploration after CT imaging. Overall, 134 patients (52 female patients, 38.8%) with a mean age of 69.2 ± 12.4 years were included into the present analysis. For all patients, the preoperative CT was used to calculate the contrast media enhancement of the adrenal glands and the spleen. RESULTS: A total of 27 patients (18.5%) died within the first 24 h and over the following 30-day 94 patients (68.6%) died. There were statistically significant differences regarding the mean values for adrenal-to-spleen ratio for 24-h mortality (p = 0.001) and 30-day mortality (p = 0.004), whereas the radiodensity of the inferior vena cava and the radiodensity of the spleen was statistically significant between survivors and non-survivors after 30 days (p = 0.037 and p = 0.028, respectively). In Cox regression analysis, mean adrenal radiodensity was associated with 24-h mortality (HR 1.09, 95% CI 1.02-1.16, p = 0.01) but not with 30-day mortality (HR 1.03, 95% CI 0.99-1.07, p = 0.13). CONCLUSION: The contrast media enhancement of the adrenal gland is associated with the 24-h and 30-day mortality in patients with AMI. However, the prognostic relevance for translation into clinical routine needs to be validated in other cohorts.

Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling for the subtyping of primary aldosteronism: a prospective study.

OBJECTIVE: Adrenal venous sampling (AVS) is key for primary aldosteronism subtype identification. However, the value of adrenocorticotropic hormone (ACTH) stimulation in AVS is still controversial. METHODS: In this prospective study, we investigated the role of continuous ACTH infusion on the performance and interpretation of bilateral simultaneous AVS using a standard protocol in 59 primary aldosteronism patients. We analyzed the selectivity index and lateralization index in AVS pre and post-ACTH and estimated the prognosis of patients who underwent adrenalectomy with different cutoff points of lateralization index post-ACTH. RESULTS: The confirmed success rate of bilateral adrenal vein catheterization increased from 84% pre-ACTH to 95% post-ACTH. Fifty percent of the patients had a decline in lateralization index post-ACTH, 30% of patients showed unilateral primary aldosteronism pre-ACTH but bilateral primary aldosteronism post-ACTH according to lateralization index at least 2 pre-ACTH and lateralization index at least 4 post-ACTH. The outcomes of the patients with primary aldosteronism after adrenalectomy indicated that all patients achieved clinical and biochemical success regardless of lateralization index at least 4 or less than 4 post-ACTH. Receiver operating characteristic curves showed that lateralization index cutoff 2.58 post-ACTH stimulation yielded the best threshold in lateralization with a sensitivity of 73.1% and a specificity of 92.9%. CONCLUSION: ACTH stimulation increased the AVS success rates in patients with primary aldosteronism, reduced lateralization index in some cases and decreased the proportion of identified unilateral primary aldosteronism, resulting in some patients losing the opportunity for disease cure. Compared with lateralization index at least 4, a lower cutoff point of lateralization index at least 2.58 after ACTH stimulation has better accuracy of lateralization diagnosis.

Determination of three C18-oxygenated steroids in adrenal lesion segments in primary aldosteronism by super-selective adrenal venous sampling and LC/ESI-MS/MS.

Super-selective adrenal venous sampling (ssAVS) can collect the adrenal tributary venous blood in the aldosterone (ALD)-hypersecreting segments in primary aldosteronism. The concentrations of the C18-oxygenated steroids, especially 18-oxocortisol (18-oxoF), in the lesion segments might be more useful indices than those in the peripheral or adrenal central veins (current candidate indexes) for the differential diagnosis of unilateral ALD-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). To verify this hypothesis, we developed a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method for simultaneously quantifying ALD, 18-oxoF and 18-hydroxycortisol in the adrenal tributary venous serum sample collected by ssAVS (ssAVS serum) and compared their concentrations between APA and BAH patients. Only deproteinization was required for a 10 µl sample prior to the LC/ESI-MS/MS analysis. Endogenous corticoids did not interfere with the quantifications, and the intra-assay and interassay precisions (≤ 8.3%) and accuracies (94.2-102.7%) were acceptable. The clinical study revealed that the 18-oxoF concentration was significantly higher in the ALD-producing tumor tissues (from APA patients) than in the hyperplastic tissues (from BAH patients). However, in conclusion, the 18-oxoF concentration in the ssAVS serum sample can be a rough indication but cannot be decisive for the differential diagnosis between APA and BAH owing to the significant individual difference.

Adrenal venous sampling criteria for chemiluminescent enzyme immunoassay as a preferable alternative to radioimmunoassay in primary aldosteronism.

Plasma aldosterone concentration (PAC) was routinely measured using radioimmunoassay (RIA); however, the RIA kit was discontinued in March 2021 in Japan. This study examined PAC conversion in adrenal venous sampling (AVS) and AVS criteria when measured using chemiluminescent enzyme immunoassay (CLEIA). PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) of 63 patients with primary aldosteronism was measured using RIA (Spac-S aldosterone kit; Fujirebio Inc.) and CLEIA (Lumipulse Presto Aldosterone; Fujirebio Inc.). PAC of 70 AVS samples was also measured using liquid chromatography-mass spectrometry (LC-MS/MS, ASKA Pharma Medical Co., Ltd.). PAC conversion formulas were determined for each AVS sample assay. PAC measured using CLEIA was significantly correlated with that measured using RIA (correlation coefficient = 0.971). The PAC conversion formula was PAC (CLEIA) = PAC (RIA) × 0.772 - 1,199 pg/mL. The PAC of 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. PAC measured using CLEIA was also correlated with that measured using LC-MS/MS, and the PAC conversion formula was PAC (CLEIA, pg/mL) = 0.97 × PAC (LC-MS/MS, pg/mL) + 211. The inter-assay coefficient of variability (CV) was 1.1-1.3% and intra-assay CV was 1.0-1.7%, measured using CLEIA. The PAC conversion formula for AVS samples was obtained using CLEIA and RIA, and the conversion formula was different from that for peripheral blood. PAC values measured by CLEIA showed preferable accuracy and high concordance with those measured by LC-MS/MS, even in AVS samples. The study outcomes are useful for interpreting AVS results using non-RIA measurement methods.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

Adrenal Vein Sampling: Does the Location of the Non-adrenal Venous Sample Matter?

PURPOSE: Adrenal vein sampling (AVS) is used to lateralise and differentiate unilateral from bilateral aldosterone production in primary aldosteronism. The adrenal venous samples are standardised to a peripheral or low inferior vena cava (IVC) sample and compared. It is unknown whether the location of the non-adrenal sample affects the results. This study compares AVS results standardised to the low IVC and right external iliac vein (REIV). METHODS: Patients who underwent AVS between March 2021 and May 2023 were included. All procedures were undertaken by a single operator (AA). Demographic data and AVS results were collected from patients' electronic records. Catheterisation success and lateralisation were assessed using both low IVC and REIV samples. Equivalence test was used to compare the cortisol and aldosterone levels. RESULTS: Eighty-one patients, (M: F = 38:43), aged between 29 and 74 were included. Bilateral successful adrenal vein cannulation was achieved in 79/81 (97.5%) cases. The mean cortisol levels from the REIV were statistically equivalent although there was a small and not biologically significant difference from the low IVC (respective geometric means 183 nmol/l vs. 185 nmol/l, p = 0.015). This small difference in cortisol may be due to accessory adrenal venous drainage into the IVC. The aldosterone and aldosterone/cortisol ratios were statistically equivalent. There was no discordance in selectivity or lateralisation when the IVC or REIV measurements were used. CONCLUSION: The IVC and REIV samples may be used interchangeably during AVS.

Imaging Concordance With Vein Sampling for Primary Aldosteronism: A Cohort Study and Literature Review.

INTRODUCTION: Adrenal venous sampling (AVS) is used to distinguish unilateral from bilateral aldosterone hypersecretion as a cause of primary aldosteronism (PA). Unilateral disease is treated with adrenalectomy and bilateral hypersecretion managed medically. METHODS: We performed a single institution retrospective cohort study of adult patients undergoing adrenalectomy for PA from July 2013 to June 2022. Concordance of imaging findings with AVS was evaluated. Statistical analysis was performed with Mann-Whitney U and chi-squared Fisher's exact. Literature review performed via triple method search strategy. RESULTS: Twenty-one patients underwent AVS and adrenalectomy for PA. Two patients did not have imaging findings and 19 were localized with an adenoma. For patients with image localization, AVS was concordant in nine, discordant in four, and nondiagnostic in six. For patients with discordant findings, age range was 35.8 to 72.4 y compared with concordant patient age range of 49.8 to 71.7 y. Overall discordance between imaging results and AVS was 40%. The aldosterone level was associated with concordance with a median of 52 ng/dL compared with 26 ng/dL if discordant (P = 0.002). There was a significant reduction in antihypertensive medications for the entire cohort from a median of three medications (interquartile range 2-4) to 1 medication (interquartile range 1-2), P < 0.001. CONCLUSIONS: In this cohort, 40% of patients with selective AVS had discordant imaging and AVS results. Aldosterone level was associated with concordance. Hypertension was significantly improved with a median decrease of two antihypertensives. Our results support performance of AVS on all candidates for adrenalectomy for PA.

Multiple radiologist review of adrenal CT still frequently misses lateralized surgical primary aldosteronism.

Patients with primary aldosteronism (PA) have increased morbidity and mortality compared to those with essential hypertension. Accurate detection of lateralized PA is important so that affected patients can receive potentially curative adrenalectomy. However, around 40% of patients with lateralized PA have "normal" adrenal glands on computed tomography (CT). Additional independent review of imaging has been shown to improve diagnostic accuracy in many areas of imaging. Therefore, the authors sought to establish if multi-reader re-assessment of previously reported normal CT scans would result in increased detection of surgically remediable disease. The authors found that re-assessment of CT imaging by one, two, or three additional radiologists (or a combination thereof) slightly increased the detection of lateralized disease, but these differences were not statistically significant (p > .05). Readers had low inter-observer agreement (kappa = 0.17). If detection of a discrete nodule on CT was made a prerequisite for adrenal vein sampling (AVS), a second read by another reviewer would still result in an excess of missed cases (84.2%, 36.8%, and 65.8%, respectively, for each of the three independent reviewers). Therefore, a "normal" CT does not preclude the possibility of lateralized PA. Adrenal vein sampling should still be strongly considered wherever available and whenever surgery is considered for treatment of PA, irrespective of CT findings.

Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism.

OBJECTIVE: Adrenal venous sampling (AVS) is recommended for identifying the subtype of primary aldosteronism before making a surgical treatment decision, but failed cannulation of one adrenal vein is common. To evaluate whether using results of one adrenal vein during AVS could accurately predict unilateral primary aldosteronism. METHODS: A retrospective study was conducted in primary aldosteronism patients receiving bilaterally or unilaterally successful AVS. The aldosterone-cortisol ratio from the adrenal vein divided by the aldosterone-cortisol ratio from the inferior vena cava (IVC) was calculated as the AV/IVC index. RESULTS: The study examined 455 patients with primary aldosteronism, including 347 patients with unilateral primary aldosteronism. Among them, 250 and 125 patients received non- adrenocorticotropic hormone (ACTH) and ACTH-stimulated AVS, respectively, and 80 patients received both forms of AVS. Under non-ACTH-stimulated AVS, AUC of the AV/IVC index to diagnose ipsilateral and contralateral primary aldosteronism were 0.778 and 0.924, respectively. The specificity was 100% for both, with sensitivities of 5 and 26%, respectively, when using cutoffs of 17.05 to diagnose ipsilateral primary aldosteronism and 0.15 to diagnose contralateral primary aldosteronism. When using cutoffs of 3.60 and 0.70, the specificity decreased, but if combined with CT results (ipsilateral or contralateral adrenal nodules larger than 10 mm), the specificity could be maintained at 99%, with sensitivities of 33 and 45%, respectively. Under ACTH-stimulated AVS, the AV/IVC index showed similar accuracy to diagnose ipsilateral and contralateral primary aldosteronism. CONCLUSION: The unilateral AV/IVC index can be used to diagnose unilateral primary aldosteronism during AVS. Combining CT results can increase the accuracy further.