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Lateralization index results in 76 patients with and without adrenocorticotropic hormone (ACTH) stimulation.
Source publication
The aim of this study is to determine the accuracy of adrenal vein sampling (AVS) with and without adrenocorticotropic hormone (ACTH) stimulation to distinguish between unilateral and bilateral primary hyperaldosteronism (PA). Retrospective analysis of a prospective database from a referral center between 1984 and 2009, 76 patients had simultaneous...
Context in source publication
Context 1
... the left adrenal vein, the SI ratio was higher with ACTH stimulation compared to without (97.4% vs. 59.2%) with no statistically significant difference (p = 0.084). The mean LI was 34.7 with ACTH stimulation and 19.6 without ACTH stimulation (Table 3). The LI >2 ratio was significantly higher with ACTH stimulation compared to without (97.4% and 90.8%, respectively, p = 0.007). ...Similar publications
To determine factors associated with lateralization in primary aldosteronism (PA). The clinical data for PA patients hospitalized at the First Affiliated Hospital of Guangxi Medical University from October 2016 to March 2021 were included in this study. They were classified according to results derived from computed tomography (CT): bilaterally nor...
Objective: Primary hyperaldosteronism (PA) is an important cause of secondary hypertension. One of the most crucial steps in the management of patients with PA is the determination of the laterality of aldosterone production (unilateral or bilateral disease). This study aimed to determine the success rate of adrenal venous sampling (AVS) and the co...
Adrenal venous sampling (AVS) is the gold standard for identifying curable unilateral aldosterone excess in primary aldosteronism (PA). Studies have demonstrated the value of steroid profiling through liquid chromatography–tandem mass spectrometry (LC–MS/MS) in AVS interpretation. First, the performance of LC–MS/MS and immunoassay in assessing sele...
Background
Adrenal Computed tomography (CT) is a useful tool for locating adrenal lesion in primary aldosteronism(PA) patients. However, adrenal vein sampling(AVS) is considered as a gold standard for subtype diagnosis of PA. The aim of this study was to investigate the consistency of CT and AVS for the diagnosis of PA subtypes and evaluate the con...
Adrenal cortical carcinoma (ACC) is a rare cancer (1-2/million) that presents with hormone overproduction in 60% of cases. Presentation of ACC with multiple hormone syndromes from different adrenal zones is rare. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new...
Citations
... The AVS procedure was performed under adrenocorticotropic hormone stimulation [22] . Samples from the right and left adrenal vein and inferior vena cava were drawn twice or three times. ...
Background
Adrenal Computed tomography (CT) is a useful tool for locating adrenal lesion in primary aldosteronism(PA) patients. However, adrenal vein sampling(AVS) is considered as a gold standard for subtype diagnosis of PA. The aim of this study was to investigate the consistency of CT and AVS for the diagnosis of PA subtypes and evaluate the concordance of surgical outcomes.
Materials and methods
This retrospective study included 264 PA patients having both CT and AVS. Diagnostic consistency between CT and AVS was accessed, and clinical and biochemical outcomes were evaluated at 6 months after adrenalectomy.
Results
Of all, 207 (78%) had CT unilateral lesion, 32 (12%) CT bilateral lesion, and 25 (9%) CT bilateral normal findings. Among CT unilateral lesion group, 138 (67%) had ipsilateral AVS lateralization. For CT bilateral lesion and bilateral normal, AVS unilateral lateralization was found in 17 (55%) and 2 (8%), respectively. The consistency between CT lesion and AVS lateralization including CT unilateral with AVS ipsilateral, and CT bilateral lesion with AVS bilateral patients was 63.8%(152/238). Of 77 patients with available data out of 138 patients who underwent adrenalectomy with consistency between CT and AVS, clinical success rate was 96%, for 17 inconsistency patients out of 22 patients who underwent adrenalectomy, clinical success rate was 94% after adrenalectomy following the lateralization result of AVS.
Conclusion
CT is a useful tool to diagnose the adrenal lesion in PA patients. However, AVS is more sufficient to detect the unilateral PA subtype which could provide curable treatment to surgical candidates of PA such that AVS can identify patients with contralateral PA in CT unilateral lesion and unilateral PA in CT bilateral lesion. The surgical outcome was successful when adrenalectomy was performed according to the AVS lateralization result.
... Meanwhile, the effect of ACTH on LR is variable in the literature, with possibly a general tendency to a decreased LR following ACTH administration compared to baseline [19,54,[56][57][58]. One study, however, found a tendency to increased ACTH-stimulated LR [59]. Similarly, many studies examined the discordance rate of LR between individual unstimulated and ACTH-stimulated samplings. ...
... Similarly, many studies examined the discordance rate of LR between individual unstimulated and ACTH-stimulated samplings. This discordance varies greatly between studies, from around 9 % [59,60] up to 41 % [61]. In their review of the last 12 studies, Yozamp et al. estimated the discordance in lateralization to be around 26 % [56]. ...
... On the other hand, only 29 % and 67 % had complete and partial clinical success, respectively [65]. This discrepancy between biochemical and clinical success, and between complete and partial clinical success, is consistent across all studies of the post-Primary Aldosteronism Surgical Outcome (PASO) criteria era [11,19,56,58,59,61,[64][65][66][67]. This trend is difficult to extrapolate to studies with post-operative outcomes of the pre-PASO era, as the criteria for PA cure varied from one study to another. ...
Adrenal vein sampling (AVS) is recommended for subtyping primary aldosteronism (PA) to identify lateralized or bilateral sources of aldosterone excess, allowing for better decision-making in regard to medical or surgical management on a case-by-case basis. To date, no consensus exists on protocols to be used during AVS, especially concerning sampling techniques, the timing of sampling, and whether or not to use adrenocorticotropic hormone (ACTH) stimulation. Interpretation criteria for selectivity, lateralization, and contralateral suppression vary from one expert center to another, with some favoring strict cut-offs to others being more permissive. Clinical and biochemical post-operative outcomes can also be influenced by AVS criteria utilized to indicate surgical therapy.
In this review, we reanalyze studies on AVS highlighting the recent pathological findings of frequent micronodular hyperplasia adjacent to a dominant aldosteronoma (APA) overlapping with bilateral idiopathic hyperaldosteronism (IHA) etiologies, as opposed to the less frequent unilateral single aldosteronoma. The variable expression of melanocortin type 2 receptors in the nodules and hyperplasia may explain the frequent discordance in lateralization ratios between unstimulated and ACTH- stimulated samples. We conclude that aldosterone values collected during simultaneous bilateral sampling, both at baseline and post-ACTH stimulation, are required to adequately evaluate selectivity, lateralization, and contralateral suppression during AVS, to better identify all patients with PA that can benefit from a surgical indication. Recommended cut-offs for each ratio are also presented.
... 11,12 The utilization of ACTH may also lower the lateralization index (LI), which is the ratio of aldosterone/cortisol (A/C) value in dominant adrenal vein and non-dominant adrenal vein, and confuses the cut-off value between lateralized diseases and bilateral ones. 13 Several studies explore the effect of ACTH on AVS procedure 7-10, [14][15][16][17][18][19][20][21][22] and some describe the effect on postoperation outcome based on biochemical data. 11,12 Nevertheless, it is frustrating that the studies are usually self-controlled and not able to compare the post-operation outcome, or they do not focus on the clinical outcome after adrenalectomy. ...
Adrenal venous sampling (AVS) is thought to be the gold standard for primary aldosteronism (PA) subtype discrimination, during which the application of adrenocorticotropic hormone (ACTH) arouses heated debate. We aimed to identify the effect of ACTH on AVS and surgical outcomes. After propensity score matching (PSM), a total of 220 patients diagnosed with PA and completed AVS were included (110 without ACTH stimulation and 110 with ACTH stimulation). According to AVS results, surgeries were conducted in appropriate patients. ACTH stimulation significantly increased almost all selectivity index (SI) in both left adrenal vein (LAV) and right adrenal vein (RAV). We discovered that aldosterone/cortisol (A/C) value on dominant side significantly reduced after ACTH stimulation, with a reduction in lateralization index (LI) observed. Finally, 39 patients in unstimulated group and 32 patients in stimulated group completed surgery and enough follow-up. The comparison between surgical outcomes with and without ACTH stimulation was analyzed and the difference was not significant (p = .464). In conclusion, ACTH application significantly lowered A/C value instead of the relative aldosterone secretion index (RASI) value on dominant side, which did not yield superior surgical outcomes and might render confusing AVS interpretation.
... Some centers use unilateral sequential sampling, while others use simultaneous bilateral sampling [12]. Different centers perform AVS with or without ACTH stimulation [13,14]. There are no specific guidelines or recommendations regarding whether ACTH stimulation is necessary [15,16]. ...
... Therefore, anatomical and physiological factors may influence the SI even if the catheterization was correct at baseline; this problem could be solved by stimulating cortisol secretion through ACTH. At present, there are no standardized ACTH stimulation protocols, and methods of ACTH stimulation include a high-dose bolus, infusion after a bolus and a bolus after infusion [13][14][15][16][20][21][22][23][24][25]. With a very low-dose bolus [16] after infusion and sustained infusion (250 μg/30 min) [20], as performed at some centers, no difference was observed in the SI between baseline and after ACTH. ...
... With a very low-dose bolus [16] after infusion and sustained infusion (250 μg/30 min) [20], as performed at some centers, no difference was observed in the SI between baseline and after ACTH. With the other methods of administration, the SI was significantly increased, and the greatest increase in adrenal cortisol secretion was stimulated by infusion after a bolus [13][14][15][16][20][21][22][23][24][25]. Our center performs simultaneous bilateral catheterization using a medium-dose ACTH bolus (125 μg), followed by a continuous intravenous infusion (125 μg/h); throughout the process, the catheter is not moved. ...
The aim of the study was to investigate the significance and influence of adrenocorticotropic hormone (ACTH) stimulation in primary aldosteronism (PA) patients with simultaneous bilateral adrenal vein sampling (AVS). All patients diagnosed with PA underwent simultaneous bilateral AVS with ACTH. In 95 patients, the post-ACTH SI significantly increased (p<0.001), and it gradually decreased from t10–t30 after ACTH stimulation (p<0.001). The unsuccessful catheterization decreased after ACTH stimulation. Time points within 20 min after ACTH stimulation were better for sampling, and the selectivity did not increase over longer periods. According to lateralization before and after ACTH stimulation, the patients could be divided into 3 groups (U, unilateral; B, bilateral): U/U , U/B or B/U, and B/B. Compared with the U/U group, in the U/B or B/U and B/B groups, the lateralization index (LI) was lower both at baseline and after ACTH stimulation (p<0.0001), the contralateral index (CLI) was higher after ACTH stimulation (p<0.003), the serum potassium level was higher (p<0.001), and the carbon dioxide combining power (CO2CP) and base excess (BE) levels were lower. In conclusion, in simultaneous bilateral AVS, ACTH stimulation had significant effects on increasing the catheterization selectivity. Lateralization change was observed after stimulation. After ACTH stimulation, fewer patients could be diagnosed with lateralized PA. Patients with consistent lateralized PA showed a more serious phenotype.
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.
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.
Importance
Adrenal venous sampling (AVS) is usually recommended to distinguish between unilateral and bilateral primary aldosteronism (PA) before definitive surgical or medical treatment is offered. Whether a treatment decision based on AVS with or without corticotropin (ACTH) stimulation leads to different biochemical and clinical remission rates in patients with PA remains unclear.
Objective
To evaluate whether treatment decisions based on AVS with or without ACTH stimulation lead to different biochemical and clinical remission rates in patients with PA.
Design, Setting, and Participants
This randomized clinical trial (RCT) was conducted at a tertiary hospital in China from July 8, 2020, to February 20, 2023, among patients with PA aged 18 to 70 years. Patients were followed up for 12 months after the initiation of treatment. An intention-to-diagnose analysis was conducted.
Interventions
Patients were randomly assigned to undergo either ACTH-stimulated or non–ACTH-stimulated AVS.
Main Outcomes and Measures
The primary end point was the proportion of patients with complete biochemical remission after 12 months of follow-up. Secondary outcomes included the proportion of patients who achieved complete clinical remission after 12 months of follow-up, dosages of antihypertensive agents, rate of successful bilateral AVS, and adverse events.
Results
Of 228 patients with PA, 115 were randomized to the non–ACTH-stimulated group (median age, 50.0 years [IQR, 41.0-57.0 years]; 70 males [60.9%]) and 113 to the ACTH-stimulated group (median age, 50.0 years [IQR, 43.5-56.5 years]; 63 males [55.8%]). A total of 68 patients (59.1%) underwent adrenalectomy in the non-ACTH group and 65 (57.5%) in the ACTH group. There was no significant difference in the proportion of patients with complete biochemical remission who were managed on the basis of AVS with vs without ACTH stimulation (with: 56 of 113 [49.6%]; without: 59 of 115 [51.3%]; P = .79). There also was no significant difference in the proportion of patients who achieved complete clinical remission between the non-ACTH and ACTH groups (26 of 115 [22.6%] and 31 of 113 [27.4%], respectively; P = .40). The intensity of therapy with antihypertensives, successful catheterization of bilateral adrenal veins, and incidence of adverse events did not significantly differ between the non-ACTH and ACTH groups.
Conclusions and Relevance
In this RCT, treatment of PA on the basis of non–ACTH-stimulated or ACTH-stimulated AVS did not lead to significant differences in clinical outcomes for the patients. These results suggest that ACTH stimulation during AVS may not have clinical benefit, at least in the Chinese population.
Trial Registration
ClinicalTrials.gov Identifier: NCT04461535
Context:
Primary aldosteronism (PA) is the most common endocrine cause of hypertension. The final diagnostic step involves subtyping, using adrenal vein sampling (AVS), to determine if PA is unilateral or bilateral. The complete PA diagnostic process is time and resource intensive, which can impact rates of diagnosis and treatment. Previous studies have developed tools to predict bilateral PA before AVS.
Objective:
Evaluate the sensitivity and specificity of published tools that aim to identify bilateral subtypes of PA.
Methods:
Medline and Embase databases were searched to identify published models that sought to subtype PA, and algorithms to predict bilateral PA are reported. Meta-analysis and meta-regression were then performed.
Results:
There were 35 studies included, evaluating 55 unique algorithms to predict bilateral PA. The algorithms were grouped into 6 categories; those combining biochemical, radiological and demographic characteristics (A), confirmatory testing alone or combined with biochemical, radiological and demographic characteristics (B), biochemistry results alone (C), adrenocorticotropic hormone stimulation testing (D), anatomical imaging (E) and functional imaging (F). Across the identified algorithms, sensitivity and specificity ranged from 5-100% and 36-100%, respectively. Meta-analysis of 30 unique predictive tools from 32 studies showed that the Group-A algorithms had the highest specificity for predicting bilateral PA, while Group-F had the highest sensitivity.
Conclusions:
Despite the variability in published predictive algorithms, they are likely important for decision-making regarding the value of AVS. Prospective validation may enable medical treatment upfront for people with a high likelihood of bilateral PA without the need for an invasive and resource-intensive test.
Objective
Primary aldosteronism (PA) is a common form of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for subtyping PA. This study aimed to determine whether there is a difference between immunoassays and liquid chromatography-mass spectrometry (LC-MS/MS) methods for measuring cortisol levels that affect the judgement of AVS.
Design
This was a retrospective study.
Patients
Included 72 patients who were diagnosed with PA and had undergone AVS.
Measurements
Patients were grouped according to whether they received adrenocorticotropic hormone (ACTH) stimulation during AVS, and the cortisol results were measured using immunoassay and LC-MS/MS.
Results
There were 48 patients in the without ACTH stimulation group and 24 in the post-ACTH stimulation group during AVS (bilateral adrenal vein cannulation success rate, 56.25% vs. 83.33%). ACTH stimulation was beneficial for increasing the success rate of AVS (p < .001). Immunoassays were linearly correlated with LC-MS/MS when cortisol concentrations were <1750 nmol/L (r = .959, p < .001). When cortisol concentrations were >17,500 nmol/L, no correlation was found between the two methods (p = .093). The two methods were consistent for the detection of cortisol for evaluating the success of cannulation for AVS. Five percent of patients showed discordant lateralization of aldosterone production according to the cortisol LC-MS/MS and immunoassay results in the without ACTH group, and 15% showed discordant lateralization in the post-ACTH group.
Conclusions
The immunoassay method can be used to determine whether cannulation is successful. The final decision for lateralization may be more appropriate based on LC-MS/MS results.
Objective:
This study aimed to investigate the impact of indices of adrenal venous sampling (AVS) on postsurgical outcomes in patients with primary aldosteronism (PA).
Design and patients:
This retrospective study determined biochemical and clinical outcomes based on ACTH-stimulated AVS parameters (lateralisation index [LI], contralateral ratio [CLR], and ipsilateral ratio [ILR]) in 251 patients with PA at 3 months after surgery.
Results:
Modified complete biochemical success was achieved in 8 of 12 (66.7%) patients with LI = 3-4, 39 of 47 (83.0%) with LI = 4-10, and 155 of 169 (91.7%) with LI ≥ 10 (p = .004 for trend). Modified complete biochemical success was achieved in 29 of 38 (76.3%) patients with CLR ≥ 1 and ILR ≤ 2, 73 of 86 (84.9%) with CLR = 0.25-1 and ILR > 2, and 100 of 104 (96.2%) with CLR < 0.25 and ILR > 2 (p = .001 for trend). After adjusting for confounders, modified complete biochemical success was associated with an LI ≥ 10 (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 1.33-29.93) using LI = 3-4 as a reference and combined CLR < 0.25 and ILR > 2 (OR = 11.49; 95% confidence interval [CI] = 2.49-53.01) using combined CLR ≥ 1 and ILR ≤ 2 as a reference. Using combined CLR ≥ 1 and ILR ≤ 2 as a reference, complete clinical success was associated with combined CLR < 0.25 and ILR > 2 (OR = 3.10; 95% CI = 1.03-9.28) and combined CLR = 0.25-1 and ILR > 2 (OR = 4.92; 95% CI = 1.64-14.76).
Conclusion:
LI ≥ 10 may be appropriate for achieving biochemical success. With ILR > 2, CLR < 0.25, and CLR < 1 may be appropriate for achieving biochemical and clinical success, respectively.
