Adrenal vein sampling for primary aldosteronism: the assessment of selectivity and lateralization of aldosterone excess baseline and after adrenocorticotropic hormone (ACTH) stimulation

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 cannulation of bilateral adrenal veins and AVS with and without ACTH stimulation. All patients had adrenalectomies. The selectivity index (SI, cut-off value ≥2) was used for confirmation of successful cannulation of the adrenal vein. The lateralization index (LI, cut-off value >2 and >4) was used for distinguishing between unilateral and bilateral PA. The SI ratio was higher with ACTH stimulation compared to without for the right adrenal vein (p = 0.027). The LI > 2 ratio was higher with ACTH stimulation compared to without (p = 0.007). For the LI > 4 ratio, there was no difference between with and without ACTH stimulation (p = 0.239). However, for a LI > 4, 7 patients (9.2%) were not lateralized with ACTH stimulation, but they did lateralize without ACTH stimulation. AVS with ACTH stimulation is associated with a higher SI ratio compared to AVS without ACTH stimulation. However, when using LI > 4 for AVS, samples without ACTH stimulation should also be included to detect a subset of patients with unilateral disease that are not detected with ACTH stimulation.

Adrenal venous sampling (AVS) is key for primary aldosteronism subtype identification. However, the value of adrenocorticotropic hormone (ACTH) stimulation in AVS is still controversial. 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. 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%. 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.

Adrenal venous sampling (AVS) with or without adrenocorticotropic hormone (ACTH) stimulation is the test of choice to identify patients with a surgically curable subtype of primary aldosteronism (PA). Whether AVS with ACTH stimulation is more effective than AVS without ACTH stimulation remains controversial. To compare the effectiveness of AVS with ACTH stimulation and AVS without ACTH stimulation in patients with PA. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All cohort studies comparing the 2 techniques (AVS with ACTH stimulation and AVS without ACTH stimulation in patient with PA) were included in the analysis. A total of 14 studies met the inclusion criteria, and they were analyzed. AVS with ACTH stimulation did not significantly reduce the number of incorrect lateralization more than AVS without ACTH stimulation in patients with PA [OR: 0.76, 95% confidence interval (CI): 0.36, 1.59; P=0.47]. AVS with ACTH stimulation significantly reduced the number of unsuccessful cannulations of both adrenal veins more than AVS without ACTH stimulation in patients with PA (OR: 0.26, 95% CI: 0.17, 0.40; P<0.00001). For subgroup analyses, it also significantly reduced the number of unsuccessful cannulations of left adrenal vein and right adrenal vein (OR: 0.14, 95% CI: 0.06, 0.33; P<0.00001 and OR: 0.30, 95% CI: 0.12, 0.71; P=0.007, respectively). AVS with ACTH stimulation can significantly reduce the number of unsuccessful cannulations, without significantly reducing the number of incorrect lateralization. Further studies are still needed to verify these findings.

In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), adrenocorticotropic hormone (ACTH) stimulation generally increased the success rate. The effect of ACTH stimulation on the left-right differences of laterality diagnosis in AVS remains unclear. A total of 167 patients with PA underwent successful AVS were examined. Patients with autonomous cortisol secretion were excluded. The proportion of dominant side in AVS was compared before and after ACTH stimulation. Unilateral disease on AVS was defined as a lateralization index of more than 4, both before and after ACTH stimulation. Before ACTH stimulation, unilateral disease was more frequently observed on the right side than the left side (right 33.5% vs. left 13.8%, p < 0.01). After ACTH stimulation, unilateral disease was more frequently observed on the left side than the right side, without statistical significance (left 15.6% vs. right 10.8%, p = 0.20). Among the 56 patients who had right unilateral disease before ACTH stimulation, 17 patients (30.0%) also had right unilateral disease after ACTH stimulation. The affected side of AVS was changed from right unilateral to bilateral after ACTH stimulation in 34 (60.7%) out of 56 patients. These patients had milder PA and CT scans showed no nodular lesions on the right side. In AVS, ACTH stimulation not only decreased unilateral results but also shifted to the dominant side. Overestimation should be carefully considered when the surgical indication for the right adrenal gland was decided based on AVS results without ACTH stimulation.

confound, and even invert, the lateralization in about 24% of the patients, 7 for reasons that are discussed in depth elsewhere.

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.

[Figure: see text].

Adrenal vein sampling (AVS) is fundamental for subtype diagnosis in patients with primary aldosteronism. AVS protocols vary between centers, especially for diagnostic indices and for use of adrenocorticotropic hormone (ACTH) stimulation. We investigated the role of both continuous ACTH infusion and bolus on the performance and interpretation of AVS in a sample of 76 patients with confirmed primary aldosteronism. In 36 primary aldosteronism patients, AVS was performed both under basal conditions and after continuous ACTH infusion, and in 40 primary aldosteronism patients, AVS was performed both under basal conditions and after ACTH IV bolus. Both ACTH protocols determined an increase in the rate of successful cannulation of the adrenal veins. Both ACTH infusion and bolus determined a significant increase in selectivity index for the right adrenal vein and ACTH bolus for the left adrenal vein. Lateralization index was not significantly different after continuous ACTH infusion and IV bolus. In 88% and 78% of the patients, the diagnosis obtained was the same before and after ACTH infusion and IV bolus, respectively. However, the reproducibility of the diagnosis was reduced using less stringent criteria for successful cannulation of the adrenal veins. This study shows that ACTH use during AVS may be of help for centers with lower success rates, because a successful adrenal cannulation is more easily obtained with this protocol; moreover, this technique performs at least as well as the unstimulated strategy and in some cases may be even better. Stringent criteria for cannulation should be used to have a high consistency of the diagnosis.

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 selectivity and lateralization was compared. Second, the utility of the proportion of individual steroids in adrenal veins in subtyping PA was analyzed. We enrolled 75 consecutive patients with PA who underwent AVS between 2020 and 2021. Fifteen adrenal steroids were analyzed in peripheral and adrenal veins through LC–MS/MS before and after adrenocorticotropic hormone (ACTH) stimulation. Through selectivity index that was based on cortisol and alternative steroids, LC–MS/MS rescued 45% and 66% of failed cases judged by immunoassay in unstimulated and stimulated AVS, respectively. LC–MS/MS identified more unilateral diseases than did immunoassay (76% vs. 45%, P < 0.05) and provided adrenalectomy opportunities to 69% of patients judged through immunoassay to have bilateral disease. The secretion ratios (individual steroid concentration/total steroid concentration) of aldosterone, 18-oxocortisol, and 18-hydroxycortisol were novel indicators for identifying unilateral PA. The 18-oxocortisol secretion ratio of ≥0.785‰ (sensitivity/specificity: 0.90/0.77) at pre-ACTH and aldosterone secretion ratio of ≤0.637‰ (sensitivity/specificity: 0.88/0.85) at post-ACTH enabled optimal accuracy for predicting ipsilateral and contralateral disease, respectively, in robust unilateral PA. LC–MS/MS improved the success rate of AVS and identified more unilateral diseases than immunoassay. The secretion ratios of steroids can be used to discriminate the broad PA spectrum.

Adrenocorticotropic hormone administration was proposed to overcome the biases associated with pulsatile aldosterone secretion during adrenal venous sampling, but the usefulness of different protocols of stimulation was never systematically assessed. We, therefore, compared the effects of a high dose (HD; 250 microg IV as a bolus), a very low dose (VLD; 250 pg IV), and an intermediate dose (ID; 50 microg/h) of adrenocorticotropic hormone on the selectivity index (SI) and the lateralization index in primary aldosteronism patients, using the diagnosis of aldosterone-producing adenoma, based on pathology and follow-up data, as a reference. The HD (n=47) significantly increased plasma cortisol concentration in infrarenal inferior vena cava (+79%) blood and the SI on both sides (SI(RIGHT)+113% and SI(LEFT)+131%), as compared with baseline values. The ID (n=14) also markedly increased both plasma cortisol concentration inferior vena cava (+93%) and the SI (SI(RIGHT)+690% and SI(LEFT)+410%); the very low dose (n=6) had no effect on either the plasma cortisol concentration or SI. In the patients with unilateral aldosterone-producing adenoma, the increase of selectivity with the HD and ID was counterbalanced by a confounding effect on the correct identification of the aldosterone-producing adenoma side, which was attributed to the wrong side in 3.0% and 12.5% with HD and ID, respectively. In conclusion, the HD and the ID, but not the very low dose, adrenocorticotropic hormone stimulation protocol facilitated the ascertainment of selectivity of adrenal vein catheterization. However, this favorable effect was overridden by a confounding effect on the identification of lateralized aldosterone excess to the aldosterone-producing adenoma side. Hence, we do not recommend adrenocorticotropic hormone stimulation.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA subtypes include bilateral hyperplasia and unilateral PA, typically aldosterone-producing adenomas. Adrenal venous (AV) sampling (AVS) is a key step to define PA subtype and guide PA management. According current PA guidelines, most PA patients should undergo AVS, which is a challenging procedure, especially in terms of successfully cannulating the right AV. The aim of this study was to report a single tertiary center experience with AVS in PA patients. We retrospectively evaluated 84 AVS from 1984 to 2019. Sequential AVS was performed by an experienced interventional radiologist. AV and inferior vena cava (IVC) samples were obtained under cosyntropin continuous infusion. Successful catheterization was defined by a selectivity index [SI= AV/IVC cortisol (C) concentrations] ≥5. Unilateral disease was defined by a lateralization index [LI= aldosterone (A)/C ratio in the dominant AV divided by A/C in the non-dominant AV] ≥4. The relative aldosterone secretion index (RASI= A/C ratio in AV divided by A/C in IVC) was calculated in each side. A RASI <1 was defined as contralateral suppression (CS). In patients with unsuccessful AV catheterization (mostly right AV) or undetermined LI (3-4), CS was used to indicate adrenalectomy. The biochemical cure of PA after adrenalectomy was defined as the gold standard parameter to confirm unilateral disease. Successful bilateral AV catheterization was achieved in 75% of the cases. After 2015, the use of intra-procedural rapid cortisol assay improved angiographer experience and increased AVS successful rate from 52 to 80%. LI revealed unilateral and bilateral aldosterone excess in 68 and 32% of the cases, respectively. A LI ≥4 had a sensitivity of 100% and specificity of 98% to define unilateral PA among patients with successful catheterization. In addition, RASI in the non-dominant AV was significantly lower in unilateral PA according the LI when compared to bilateral cases [0.12 (0.03 to 1.18) vs. 1.1 (0.04 to 4.56), p= 0.0001]. RASI in the non-dominant AV was inversely correlated with LI (r= -0.81, p= 0.0001). A CS index ≤0.5 had a high sensitivity (90%) and specificity (94%) to define unilateral aldosterone excess. In conclusion, the LI is the most valuable parameter in AVS for PA subtyping. Additionally, CS (cut-off of 0.5) is very useful to define lateralization and can be used in cases of borderline LI or unsuccessful AV catheterization.CAPES Grant to Freitas TC.

Cosyntropin [ACTH (1-24)] stimulation during adrenal vein (AV) sampling (AVS) enhances the confidence in the success of AV cannulation and circumvents intraprocedure hormonal fluctuations. Cosyntropin's effect on primary aldosteronism (PA) lateralization, however, is controversial. To define the major patterns of time-dependent lateralization, and their determinants, after cosyntropin stimulation during AVS. We retrospectively studied patients with PA who underwent AVS before, 10, and 20 minutes after cosyntropin stimulation between 2009 and 2018. Unilateral (U) or bilateral (B) PA was determined on the basis of a lateralization index (LI) value ≥4 or <4, respectively. Available adrenal tissue underwent aldosterone synthase-guided next-generation sequencing. PA lateralization was concordant between basal and cosyntropin-stimulated AVS in 169 of 222 patients (76%; U/U, n = 110; B/B, n = 59) and discordant in 53 patients (24%; U/B, n = 32; B/U, n = 21). Peripheral and dominant AV aldosterone concentrations and LI were highest in U/U patients and progressively lower across intermediate and B/B groups. LI response to cosyntropin increased in 27% of patients, decreased in 33%, and remained stable in 40%. Baseline aldosterone concentrations predicted the LI pattern across time (P < 0.001). Mutation status was defined in 61 patients. Most patients with KCNJ5 mutations had descending LI, whereas those with ATP1A1 and ATP2B3 mutations had ascending LI after cosyntropin stimulation. Patients with severe PA lateralized robustly regardless of cosyntropin use. Cosyntropin stimulation reveals intermediate PA subtypes; its impact on LI varies with baseline aldosterone concentrations and aldosterone-driver mutations.

The impact of autonomous cortisol secretion (ACS) on adrenal venous sampling (AVS) in patients with primary aldosteronism (PA) remains uncertain. This study aimed to evaluate the effects of ACS on success and lateralization of AVS. From the Japan Primary Aldosteronism Study-II, 872 PA patients with adrenal nodular lesions on computed tomography (CT) who underwent a 1-mg dexamethasone suppression test (DST) were included. ACS was defined as a post-DST cortisol level ≥1.8 μg/dL. AVS success was assessed using selectivity index (cutoff value 2 without, 5 with ACTH-stimulation), and lateralization was determined using lateralization index (cutoff value 2 without, 4 with ACTH-stimulation). Among 872 patients, 283 (32.4%) had ACS. After ACTH-stimulation, AVS success rate was significantly lower in ACS group than in non-ACS group (84.8% vs. 91.0%, p < 0.01), while no significant difference was observed before ACTH-stimulation. Among 524 patients with successful AVS both before and after ACTH-stimulation, 161 (30.7%) had ACS. The proportion of unilateral results did not differ significantly between ACS and non-ACS groups either with or without ACTH. Concordance between AVS and CT laterality was significantly lower in ACS group only without ACTH-stimulation (44.1% vs. 61.7%, p < 0.01). In patients with post-DST cortisol ≥5 μg/dL, reverse AVS-CT laterality was significantly more frequent than in those with cortisol <1.8 μg/dL both with and without ACTH-stimulation. In conclusion, ACS was associated with a lower AVS success rate with ACTH-stimulation, had no impact on rate of unilateral results, but reduced AVS-CT concordance, especially in patients with higher post-DST cortisol levels.

HomeHypertensionVol. 54, No. 3Adrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAdrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling Masayuki Tanemoto, Eikan Mishima, Yoichi Takeuchi and Takaaki Abe Masayuki TanemotoMasayuki Tanemoto Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Search for more papers by this author , Eikan MishimaEikan Mishima Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Search for more papers by this author , Yoichi TakeuchiYoichi Takeuchi Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Search for more papers by this author and Takaaki AbeTakaaki Abe Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Search for more papers by this author Originally published20 Jul 2009https://doi.org/10.1161/HYPERTENSIONAHA.109.137141Hypertension. 2009;54:e23Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 20, 2009: Previous Version 1 To the Editor:We read with interest the article by Seccia et al,1 which investigated the effect of adrenocorticotropic hormone stimulation during adrenal vein sampling on the identification of lateralized aldosterone excess in primary aldosteronism. The authors concluded that a high or an intermediate dose of adrenocorticotropic hormone stimulation lowered the correct identification of the aldosterone-producing adenoma (APA) side. However, the cases with the lowered identification by the stimulation might have been the cases with bilateral aldosterone excess. Reduction of blood pressure (BP) and plasma aldosterone concentration after adrenalectomy could not exclude the possibility of bilateral aldosterone excess.2Several APAs are difficult to detect on computed tomography and magnetic resonance findings, and these small APAs would not be rare.3 In the case with a small APA in the adrenal gland contralateral to the resected side, the remaining APA would retain aldosterone excess, which could result in poor BP reduction after unilateral adrenalectomy. From the BP response to adrenalectomy in the cases of Seccia et al,1 we suspect that several of them might have had small APAs in the contralateral sides. Furthermore, in some cases, the plasma aldosterone concentration after adrenalectomy remained at >12.1 ng/dL (the value taken for aldosterone excess before adrenalectomy), presumed from its values (median: 10.1; range: 2.3 to 15.8 ng/dL). We suspect that these cases might have been the cases with lowered identification by the stimulation. Reduction of BP and plasma aldosterone concentration after adrenalectomy should be compared between the cases with and without the lowered identification. If the cases with the lowered identification had poor BP and plasma aldosterone concentration reduction, the adrenocorticotropic hormone–stimulated adrenal vein sampling would be preferable to the unstimulated one for the identification of lateralized aldosterone excess in primary aldosteronism.4DisclosuresNone.1 Seccia TM, Miotto D, De Toni R, Pitter G, Mantero F, Pessina AC, Rossi GP. Adrenocorticotropic hormone stimulation during adrenal vein sampling for identifying surgically curable subtypes of primary aldosteronism: comparison of 3 different protocols. Hypertension. 2009; 53: 761–766.LinkGoogle Scholar2 Sukor N, Gordon RD, Ku YK, Jones M, Stowasser M. Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year single center experience. J Clin Endocrinol Metab. 2009; 94: 2437–2445.CrossrefMedlineGoogle Scholar3 Rossi GP, Sacchetto A, Chiesura-Corona M, De Toni R, Gallina M, Feltrin GP, Pessina AC. Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases. J Clin Endocrinol Metab. 2001; 86: 1083–1090.CrossrefMedlineGoogle Scholar4 Tanemoto M, Suzuki T, Abe M, Abe T, Ito S. Physiological variance of corticotropin affects diagnosis in adrenal vein sampling. Eur J Endocrinol. 2009; 160: 459–463.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Bardet S, Chamontin B, Douillard C, Pagny J, Hernigou A, Joffre F, Plouin P and Steichen O (2016) SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis, Annales d'Endocrinologie, 10.1016/j.ando.2016.01.008, 77:3, (208-213), Online publication date: 1-Jul-2016. Wolley M, Gordon R, Pimenta E, Daunt N, Slater G, Ahmed A and Stowasser M (2013) Repeating adrenal vein sampling when neither aldosterone/cortisol ratio exceeds peripheral yields a high incidence of aldosterone-producing adenoma, Journal of Hypertension, 10.1097/HJH.0b013e328362add3, 31:10, (2005-2009), Online publication date: 1-Oct-2013. September 2009Vol 54, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.109.137141PMID: 19620508 Originally publishedJuly 20, 2009 PDF download Advertisement

Background: Primary aldosteronism (PA) is characterized by excessive, autonomous secretion of aldosterone from one or both adrenal glands. Identification of unilateral disease and surgical resection can lead to cure, and is dependent on accurate criteria for lateralization of excess aldosterone during adrenal vein (AV) sampling (AVS). Current evidence for AVS lateralization cut-offs using plasma aldosterone concentration (PAC) measured by LC-MS/MS and post-surgical outcomes is limited. Aim: To determine optimal cut-off criteria to define lateralization of PA on AVS based on PAC measured by LC-MS/MS post-ACTH stimulation and post-surgical outcomes data. Methods: This study involved 60 subjects with PA who had PAC measured by LC-MS/MS post ACTH-stimulation during bilaterally-cannulated AVS, underwent unilateral adrenalectomy between July 2015-July 2021 and were followed up for ≥6 months. AVS lateralization parameters (lateralization index [LI; dominant PAC/cortisol(AV) ÷ non-dominant PAC/cortisol(AV)], contralateral suppression index [CSI; non-dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)], lateralization ratio [LR; dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)] and post-surgical outcome data were examined. Complete biochemical remission (CR) of PA post-surgery was defined using PASO International Consensus Criteria. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for LI, CSI and LR based on cases who achieved CR of PA post-surgery (n=55) vs those who did not (n=5). Results: Optimal cut-off LI during ACTH-stimulated AVS to identify unilateral PA cases who achieved CR post-surgery was 5.1 (AUC=0.92, P&lt;0.001; 92.7% sensitivity, 80.0% specificity) while the optimal cut-off for CSI was 0.6 (AUC=0.887, P&lt;0.001; 82.1% sensitivity, 100.0% specificity), and for LR was 3.3 (AUC=0.695, P=0.202; 80.0% sensitivity, 80.0% specificity). Cases with LR of 2.0-3.3 also achieved CR post-surgery if it was associated with CSI &lt;0.6. Conclusion: LI of &gt;5.1 provides high sensitivity and CSI &lt;0.6 high specificity for identification of surgically curable unilateral PA during ACTH-stimulated AVS when PAC is analyzed by LC-MS/MS.