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Study population. AVS Adrenal venous sampling; PA Primary hyperaldosteronism; *Unilateral disease in the AVS was defined as a lateralization index (LI) higher than 2 or 3 without or with ACTH stimulation, respectively. Bilateral disease as a lateralization index below these thresholds; **In 17 patients with unilateral disease according to AVS, surgery was not performed for several reasons: pending of surgery; patient refusal, lateralization index between 3 and 4 with ACTH or unknown reasons
Source publication
Objective
The aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated.
Methods
A re...
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Citations
... Adrenal venous sampling (AVS) is the gold standard for diagnosing APA, but this technique is both challenging to perform and invasive, thus limiting its widespread use in clinical practice [7]. Noninvasive diagnostic methods are therefore needed, particularly because the diagnosis of APA versus NF-AA will affect treatment options. ...
Objective
To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs).
Methods
Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin–stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram.
Results
A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675–0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792–1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807–1.000).
Conclusion
A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.
... Limitations and complications of AVS Unfortunately, AVS is not available in all centers, and in those where it is provided, there may be some that do not perform enough tests to acquire the experience to offer good results. Even in experienced groups, technical success in terms of sample selectivity is highly variable [138,[144][145][146][147][148][149][150] (Table 6), at the expense of failures, mainly in the catheterization of the right adrenal vein. Some studies [151,152] demonstrate high specificity (100%) but low sensitivity (50%) when using the ratio Aldosterone ÷ cortisol Unilateral vein / Aldosterone ÷ cortisol inferior vena cava (IVC). ...
Highlights
Following a positive screening test, no further studies are needed for diagnosis of PA if a plasma aldosterone concentration (PAC) > 20 ng/dL and a low circulating direct renin or plasma renin activity (PRA) are detected in a patient with spontaneous hypokalemia.
In all other patients, one (or more) of four different tests is (are) currently recommended: the fludrocortisone suppression test, the oral salt loading test, the intravenous saline test, and/or the captopril challenge test.
In all cases, hypokalemia must be corrected prior to testing.
Interfering medication must be progressively withdrawn before testing, while introducing alpha-1 adrenergic blockers, long-acting non-dihydropyridine calcium antagonists, and/or hydralazine as needed for control of hypertension.
All but the captopril challenge test run the risk of inducing hypokalemia, fluid overload, and a worsening of hypertension.
In the case of borderline results, the initial test employed can be repeated, or a second test performed. Patients with both a negative saline infusion and captopril challenge test appear to be at a low risk for harboring unilateral disease, whereas those positive for both are more likely to exhibit unilateral aldosterone secretion than when tests render conflicting results.
Patients showing a positive screening aldosterone to renin ratio (ARR) with normal/high PAC and a low renin/PRA, yet with negative diagnostic testing, presenting mild hyperaldosteronism, can benefit from targeted therapy of hypertension with mineralocorticoid receptor antagonists.
... In Pitfalls in the preoperative and postoperative workup of patients with primary aldosteronism an available AVS (7). The criteria for using AVS are quite heterogeneous across centers. ...
... The clinical application of AVS is founded on the premise that unilateral PA is characterized by lateralized aldosterone production, whereas bilateral PA is characterized by symmetrical hormone production. However, as the SPAIN-ALDO registry showed that AVS is still an underused technique in patients with PA (only 35% of PA cases underwent to AVS) and that the low experience and success rate in AVS partially justify these results [58]. Therefore, more training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA. ...
To summarize the available data on the prevalence, clinical repercussion, and diagnosis of primary aldosteronism (PA) and to discuss the SPAIN-ALDO registry’s findings, which is the largest PA patient registry in Spain.
A comprehensive review of the literature focused on the prevalence, clinical presentation and diagnosis of PA was performed.
PA is the most common cause of secondary arterial hypertension. In addition, PA patients have a higher cardio-metabolic risk than patients with essential arterial hypertension matched by age, sex, and blood pressure levels. However, despite its high prevalence and associated metabolic and cardiovascular complications, PA remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. The diagnostic investigation is a multistep process, including screening, confirmatory testing, and subtype differentiation of unilateral from bilateral PA forms. Data from the SPAIN-ALDO registry have shed light on the cardiometabolic impact of PA and about the limitations in the PA diagnosis of these patients in Spain.
The most common cause of secondary hypertension is PA. One of the most challenging aspects of the diagnosis is the differentiation between unilateral and bilateral PA because adrenal venous sampling is a difficult procedure that should be performed in experienced centers. Data from the SPAIN-ALDO registry have provided important information on the nationwide management of this pathology.
... AVS is considered the gold standard for localization diagnosis of PA. 9,20 The current Endocrine Society guideline recommends performing AVS in all patients with PA so as to identify those who may benefit from surgery. 2 However, some recent research results have cast uncertainty on the role of AVS. 15,21,22 The SPARTACUS study found no difference in clinical outcomes between CT-and AVS-based management. 15 Other studies also did not report significant differences in biochemical response and clinical resolution between patients who underwent surgery based on CT and AVS results. ...
Primary aldosteronism (PA) with unilateral adrenal disease can be cured or improved by adrenalectomy. Adrenal venous sampling (AVS) is recommended to identify patients for surgical management. However, surgeries based on computed tomography (CT) images are only advocated for PA patients aged <35 with visible unilateral adenoma. Herein, we aimed to compare CT‐based and AVS‐based surgery outcomes for PA patients with visible unilateral adenomas for different age groups. A total of 178 PA patients who underwent unilateral adrenalectomy between June 2018 and January 2021 were included in the study based on CT ( n = 54) or AVS ( n = 124). Demographics, diagnostics, and follow‐up data were retrospectively collected. Clinical and biochemical outcomes were analyzed according to Primary Aldosteronism Surgical Outcome (PASO) criteria at 1‐year follow‐up. Our results showed that complete clinical success (46.3% vs. 47.6%, p = 0.875) and complete biochemical success (88.8% vs. 91.9%, p = 0.515) were similar between the two groups. Age stratification revealed that patients >55 years old were likely to have worse biochemical outcomes; however, these were still not significantly different (21.4% vs. 8.6%, p = 0.220). Of the 114 AVS‐based patients who achieved complete biochemical success, 37 (32.4%) with bilateral normal or bilateral abnormal CT images changed treatment options according to AVS results, 1 (0.9%) avoided adrenalectomy on the wrong side. Our results indicated that surgery based on CT images might be feasible for highly selected PA patients with visible unilateral adenomas and less limited by age, while for those with normal adrenal or bilateral adrenal lesions, treatment strategy must be decided by AVS.
... In the first instance, the procedure is technically demanding, time consuming, associated with significant radiation exposure and demonstrates considerable center to center and operator to operator variability in terms of success (124,125). Successful cannulation of both adrenal veins is not achieved in up to 50% of patients and operator skill must be maintained with a critical number of procedures yearly (125,126). Historically, there was a lack of consensus on the methodology for AVS as outlined in the Adrenal Vein Sampling International Study (AVIS) that noted marked variation in technique and interpretation of results between centers-prompting the need for more definitive AVS guidelines (127). This knowledge gap was subsequently addressed by a panel of experts who published a consensus statement on the use of AVS (128). ...
Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared to blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for non-surgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine learning algorithms have shown promise in the prediction of PA subtypes, while the development of non-invasive alternatives to adrenal vein sampling (including molecular PET imaging) has made accurate localisation of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilisation, for this highly prevalent disorder.
... Adrenal venous sampling (AVS) is a decisive method for the lateralization of PA [2,6]. However, AVS is a technically challenging procedure, and the rate of catheterization failure is frequently high, especially in the right adrenal vein, due to the anatomical characteristics of this vascular region [7,8]. On the other hand, although CT or MRI are currently the default imaging tools to localize aldosterone-producing adenomas, their diagnostic performance is quite low, according to some studies [9]. ...
Purpose:
To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy.
Methods:
A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI.
Results:
A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707-0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782-0.957].
Conclusion:
The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.
Background
You Only Look Once version 5 (YOLOv5), a one-stage deep-learning (DL) algorithm for object detection and classification, offers high speed and accuracy for identifying targets.
Purpose
To investigate the feasibility of using the YOLOv5 algorithm to non-invasively distinguish between aldosterone-producing adenomas (APAs) and non-functional adrenocortical adenomas (NF-ACAs) on computed tomography (CT) images.
Material and Methods
A total of 235 patients who were diagnosed with ACAs between January 2011 and July 2022 were included in this study. Of the 215 patients, 81 (37.7%) had APAs and 134 (62.3%) had NF-ACAs’ they were randomly divided into either the training set or the validation set at a ratio of 9:1. Another 20 patients, including 8 (40.0%) with APA and 12 (60.0%) with NF-ACA, were collected for the testing set. Five submodels (YOLOv5n, YOLOv5s, YOLOv5m, YOLOv5l, and YOLOv5x) of YOLOv5 were trained and evaluated on the datasets.
Results
In the testing set, the mAP_0.5 value for YOLOv5x (0.988) was higher than the values for YOLOv5n (0.969), YOLOv5s (0.965), YOLOv5m (0.974), and YOLOv5l (0.983). The mAP_0.5:0.95 value for YOLOv5x (0.711) was also higher than the values for YOLOv5n (0.587), YOLOv5s (0.674), YOLOv5m (0.671), and YOLOv5l (0.698) in the testing set. The inference speed of YOLOv5n was 2.4 ms in the testing set, which was the fastest among the five submodels.
Conclusion
The YOLOv5 algorithm can accurately and efficiently distinguish between APAs and NF-ACAs on CT images, especially YOLOv5x has the best identification performance.
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.
Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA.
To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account.
A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy.
Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months’ follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18–0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52–1.73]).
Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.
