Unilateral Primary Aldosteronism Research Articles

FRI167 Implication Of Serotonin In The Physiopathology Of Aldosterone-Producing Adenoma

Abstract Disclosure: C. Duparc: None. M. D'agostino: None. A. Lopez: None. S. Renouf: None. E. Louiset: None. H. Lefebvre: None. In the human adrenal gland, serotonin (5-HT), released by subcapsular mast cells strongly stimulates expression of CYP11B2, encoding aldosterone-synthase and aldosterone production. The effect of 5-HT on adrenocortical cells is mediated by activation of type 4 serotonin receptor (5-HT4R) positively coupled to cAMP/protein kinase A (PKA) signaling pathway and calcium influx. Consistently, administration of cisapride, a 5-HT4R agonist, to healthy volunteers induces a significant increase in plasma aldosterone levels. In aldosterone producing adenomas (APA), the density of mast cells is enhanced in comparison with normal adrenals. Moreover, molecular studies have shown overexpression of HTR4 gene, encoding 5-HT4R, in APA tissues. Administration of cisapride to patients with APA induced more robust plasma aldosterone responses than in healthy voluntaries. These results suggest that 5-HT could play a role in physiopathology of APA. The aim of our study was to examine expression of genes and proteins involved in aldosterone production and actors of the serotonergic pathway in a series of 31 adenomas removed from patients with primary aldosteronism. We have also investigated the in vitro effect of various 5-HT4R ligands on aldosterone production by explants or cultured cells derived from adenoma tissues collected at surgery. Firstly, aldosterone synthase (AS) immunostaining allowed identification of adenoma phenotypes accordingly to the new international histopathology consensus for unilateral Primary aldosteronism. Among the 31 tissues studied, 20 were classified as classical APAs, i.e. presenting with homogenous or heterogenous AS distribution, remaining being considered as 11 non-classical APA. Expression of the gene encoding the 5-HT-synthesizing enzyme tryptophan hydroxylase was similar in APA and normal adrenals. HTR4 overexpression was more robust in classical than non-classical APAs. HTR4 mRNA levels were positively correlated to those encoding CYP11B2. In addition, 5-HT4R immunostaining was widely distributed in most APA tissues, a pattern which was not exclusively noticed in AS-positive adenomas. BIMU-8, a potent 5-HT4R agonist, strongly increased aldosterone production by perifused APA explants. This effect was blocked by administration of GR-113808, a 5-HT4R antagonist. In cultured APA cells, BIMU-8 stimulated aldosterone synthesis in a dose-dependent manner with a higher efficiency than that observed in normal adrenocortical cells. Aldosterone secretion was less strongly stimulated by prucalopride, a partial 5-HT4R agonist used in the treatment of chronic constipation. These data reveal an enhancement of the 5-HT signaling pathway in APAs in comparison with normal adrenals, suggesting that 5-HT and the 5-HT4R may participate in the pathophysiology of primary aldosteronism. Presentation: Friday, June 16, 2023

THU594 Outcome Data From Fabulas: A Feasibility Study Of Radiofrequency Endoscopic Ablation, With Ultrasound Guidance, As A Non-surgical, Adrenal Sparing Treatment For Aldosterone Producing Adenomas

Abstract Disclosure: G. Argentesi: None. X. Wu: None. A. Ney: None. E. Goodchild: None. K. Laycock: None. Y. Lee: None. R. Senanayake: None. J. MacFarlane: None. E. Ng: None. J. Kearney: None. A. Palma: None. I. Munteanu: None. J. Salsbury: None. E.D. Benu: None. P. Ebano: None. P. Wilson: None. E.M. Godfrey: None. G. Goodchild: None. J. Bestwick: None. M. Gurnell: None. H. Cheow: None. S.P. Pereira: None. W. Drake: None. M.J. Brown: None. Introduction: Primary aldosteronism (PA) is potentially curable if due to a unilateral aldosterone producing adenoma (APA), but complete clinical success after adrenalectomy is the exception. Selective radiofrequency ablation (RFA) of the APA, if safe, would lower the bar for intervention, but there are concerns about catecholamine crises, peri-adrenal catastrophes, and ablation of non-functional adenomas. Endoscopic ultrasound (EUS)-guided RFA of left-side APAs is an attractive alternative in which proximity to the stomach enables multiple, short, precise burns as the catheter is steered around the APA. Aims and Methods: We conducted a 3-centre feasibility study to determine the safety of EUS-RFA as an adrenal sparing treatment, and assess likely efficacy. The APA was visualised as increased uptake of 11C-metomidate (MTO) in a post-dexamethasone PET CT (1). Initial recruitment was limited to patients in whom surgery was contra-indicated (co-morbidities, ambiguous estimation of unilateral PA). α-and ß blockade were introduced 2 weeks prior to RFA, performed under general anaesthesia or deep sedation. Metanephrines were measured before and during RFA. Following diagnostic fine-needle aspiration (FNA), a 5-10 mm19G StarmedTM ablation probe was introduced into the APA. The primary outcome was safety, pre-specified as absence of perforation, haemorrhage, or infarction of major organs on a CT scan performed within 24-48 hours of RFA. Secondary outcomes, at 6 months post-RFA, were PASO criteria for biochemical/clinical success, changes in aldosterone/renin ratio (ARR), BP and drug doses, and in the MTO uptake on repeat scan. Results: 28 patients (21 male), age 57.9 ± 10.23, were studied. 7 patients had 2 ablations. None of the pre-specified serious adverse events occurred. Metanephrines rose in only one patient, given ephedrine and metaraminol. 2 further patients had RFA-related events which delayed discharge but rapidly resolved. 14 patients achieved complete biochemical success and 3 partial. 4 patients achieved complete clinical success and 4 partial. ARR fell from median 3975 (IQR 2090-7475) to 880 (369-2670), p<0.001. BP was unchanged, but on less treatment: number of antihypertensives and defined daily dose fell from 2.9 (95% CI 2.4-3.3) to 2 (1.5-2) and from 4.9 (3.6 -6.2) to 2.7 (1.7-3.6) respectively. In 6 patients, MTO uptake into the APA was reduced to <50% of adjacent adrenal (indicating complete ablation) whilst the latter was unchanged or minimally reduced in all patients (i.e. preserved function). APA diameter was reduced in 21/28 patients. In 13/28 FNA samples analysed to date, all were positive for CYP11B2 (8/13 strongly and 5/13 weakly positive). Conclusion: EUS-guided trans-gastric RFA is a safe alternative to adrenalectomy for the treatment of left-sided APAs. RFA is now being compared with surgery in a RCT of 110 patients with PA. 1. Wu et al. Nat Med 29:190-202, 2023. Presentation: Thursday, June 15, 2023

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

Diagnostic performance of the adrenal vein to inferior vena cava aldosterone ratio in classifying the subtype of primary aldosteronism.

Adrenal vein sampling (AVS) is the standard procedure for distinguishing unilateral primary aldosteronism (PA) from bilateral PA. In cases where only one adrenal vein is successfully cannulated, it has been suggested that subtype classification can be determined based on the ratio of the concentration of aldosterone between the adrenal vein and the inferior vena cava (AV/IVC index). However, diagnostic performance of the ipsilateral versus contralateral AV/IVC index in predicting lateralization has not been directly compared. In a retrospective cohort of 133 patients with confirmed PA who underwent successful AVS, the performance of the AV/IVC index to predict laterality was evaluated and the area under the receiver operating characteristic (AUROC) curves was calculated. In detecting left unilateral PA (n = 47), the AUROC of the right AV/IVC index (RAV/IVC) was significantly higher than the AUROC of the left AV/IVC (LAV/IVC) index (0.967 vs. 0.871, p = 0.008). In detecting right unilateral PA (n = 30), the AUROC of the LAV/IVC index tended to be higher than that of the RAV/IVC index, but the difference did not reach statistical significance (0.966 vs. 0.906, p = 0.08). In detecting left unilateral PA, the sensitivities of the RAV/IVC and LAV/IVC indices were 83% and 46%, respectively, while the specificities of both were above 90%. In detecting right unilateral PA, the sensitivities of the LAV/IVC and RAV/IVC indices were 80% and 43%, respectively, while the specificities of both were above 90%. The AV/IVC index has superior diagnostic performance in detecting contralateral unilateral PA compared to ipsilateral unilateral PA.

Validation of the Aldosteronoma Resolution Score as a Predictive Resolution Score of Hypertension After Unilateral Adrenalectomy for Primary Aldosteronism in a North-African Population.

Unilateral primary aldosteronism (UPA) is the most frequent surgically curable form of endocrine hypertension. Adrenalectomy is the cornerstone of treatment for UPA, but outcomes after surgery are variable. Aldosteronoma Resolution Score (ARS) is a four-item predictive score for the cure of hypertension after adrenalectomy for UPA and has been demonstrated to be valid in different populations. We aimed in this study to validate the accuracy of this score in a North-African population. Between 2000 and 2021, the charts of 71 Tunisian patients who underwent laparoscopic adrenalectomy for UPA were retrospectively reviewed. Postoperative outcomes were assessed using the primary aldosteronism surgical outcome (PASO) criterion. The accuracy of the ARS was determined retrospectively by receiver operating characteristic curve and area under the curve. Thirty-four patients (48%) had complete clinical success according to the PASO criteria. Multivariate regression analysis revealed that the main determinants of complete clinical success were the absence of diabetes (OR: 5.205), a BMI <30 (OR: 4.930), a number of antihypertensive medications ≤2 (OR: 8.667), a plasma ARR >332 (OR: 4.554) and an ARS score ≥3 (OR: 2.056). Cure rates were, respectively, 21.1, 51.6, and 66.6% for patients with a score ARS 0-1, 2-3, and 4-5. The AUC of the ARS was 0.837. The ARS is a sufficiently predictive score in our North-African population. It may be used preoperatively to predict the outcome after adrenalectomy in these populations.

Abstract P301: Predicting Complete Resolution Of Hypertension After Adrenalectomy In Primary Aldosteronism: A Systematic Review And Meta-analysis Of Prognostic Models. Surgical Outcome of PRimary Aldosteronism progNostic mOdels (SOPRANO) Study

Background: Unilateral primary aldosteronism (PA) is the most common surgically curable form of hypertension, despite complete clinical success after adrenalectomy being far from certain. Several presurgical factors were associated with complete resolution of hypertension (CRH). However, it remains unclear which of the available prognostic models combining those factors can be used in clinical practice to predict blood pressure-related outcomes after surgery for PA. Objectives: To identify, describe and appraise all prognostic models developed to predict CRH, and meta-analyse their predictive performances. Methods: We searched MEDLINE, Embase, and Web of Science, for development and validation studies of prognostic models according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The quality assessment used adapted TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) and PROBAST (Prediction model Risk Of Bias ASsessment Tool) criteria. After selection, we extracted descriptive statistics and aggregated area under the receiver operator curve (AUC) using meta-analysis. Results: From 25 eligible studies, we identified 12 prognostic models used for predicting CRH after total adrenalectomy in PA. We report the results for three models that had available data from at least three external validation studies: the Primary Aldosteronism Surgical Outcome (PASO) score (AUC: 0.81; 95% confidence interval [CI]: 0.74–0.86; 95% predictive interval [PI]: 0.04–1.00), Utsumi nomogram (AUC: 0.79; 95% CI: 0.72–0.85; 95% PI: 0.03–1.00), and the Aldosteronoma Resolution Score (ARS) model (AUC: 0.77; 95% CI: 0.74–0.80; 95% PI: 0.59–0.86 for all studies and AUC: 0.80; 95% CI: 0.75–0.85; 95% PI: 0.57–0.93 for the studies with the same adrenal vein sampling-guided adrenalectomy rate compared to the models meta-analyzed). Conclusions: The PASO score, Utsumi nomogram, and ARS model showed good and comparable discrimination performance to predict CRH after unilateral adrenalectomy in PA. However, unlike the ARS model, the number of external validation studies for the PASO score and the Utsumi nomogram was relatively low to draw definite conclusions.

Simple standing test without furosemide is useful in the diagnosis of primary aldosteronism

Primary aldosteronism (PA) is a well-known cause of secondary hypertension. We have long performed the simple standing test in patients with PA. On the other hand, there are few reports on the usefulness of the simple standing test in PA. This study is a single-center, retrospective, observational study. A total of 173 patients with hypertension or adrenal tumor admitted to Kawasaki Medical School were included. Eighty patients who met the exclusion criteria were excluded, and 31 patients without PA (non-PA), 26 patients with unilateral PA, and 36 patients with bilateral PA were included in the study. The simple standing test was performed after 120 min of standing or sitting followed, and the aldosterone/renin ratio (ARR) and percentage of increase plasma aldosterone concentration (%increase of PAC) was calculated. The mean ARR in the simple standing test in unilateral PA (1143 (528–2200)) and bilateral PA subjects (521 (374–765)) were significantly higher compared to non-PA subjects (152 (102–240)) (p < 0.0001, p = 0.0013, respectively). The percentage increase of PAC after standing loading was significantly lower in unilateral PA subjects (110 (96–140)) compared to non-PA subjects (187 (155–244)) (p = 0.0003), with no difference between non-PA and bilateral PA subjects (p = 0.99). The cutoff value of the ARR in the simple standing test for diagnosis of PA in this study was 364 (AUC = 0.948, sensitivity = 83.8%, specificity = 93.5%, false positive rate = 3.7%, false negative rate = 25.6%, p < 0.001), which was not inferior to the diagnostic performance of the captopril loading test. The diagnostic performance of the simple standing test for PA was not inferior to that of the captopril loading test. The percentage increase of PAC in unilateral PA subjects was significantly lower compared to bilateral PA subjects. These results demonstrate the usefulness of the simple standing test, which can be performed simultaneously with general screening tests of PA.

Predictors of successful outcome after adrenalectomy for unilateral primary aldosteronism.

Unilateral primary aldosteronism (UPA) is the most frequent surgically curable form of endocrine hypertension. Adrenalectomy is the cornerstone of treatment for UPA, but outcomes after surgery are variable. The cause of resistant hypertension after surgery is still a matter of debate. Our aim was to investigate cure rates after surgery and to evaluate preoperative factors that might influence the surgical outcome. Between 2000 and 2021, the charts of 71 Tunisian patients who underwent laparoscopic adrenalectomy for UPA were retrospectively reviewed. Preoperative medical records were collected and follow-up data (1-158 months) were registered. Antihypertensive medication doses were calculated using defined daily doses (DDD) and postoperative outcomes were assessed using the Primary Aldosteronism Surgical Outcome (PASO) criterion. Of 91 enrolled patients, 71 (59% women, mean age 46 years, median length of follow-up 21 months) were suitable for evaluation. Thirty-four patients (48%) had complete clinical success according to the PASO criteria. The most relevant factors associated with complete clinical success on univariate analysis were: absence of diabetes (p= 0.007), low body mass index (BMI) (p= 0.001), lower preoperative DDD (p= 0.01), preoperatively controlled blood pressure (p= 0.024), higher plasma aldosterone to renin ratio (ARR) (p= 0.001), adenoma subtyping (p <0.001) and aldosteronoma resolution score (ARS) (p= 0.002). Multivariate regression analysis showed that the major predictors of complete clinical success were absence of diabetes (OR: 5.205), a BMI < 30 (OR: 4.930), a plasma ARR > 332 (OR: 4.554) and an ARS ≥ 3 (OR: 2.056). Complete and partial clinical response rates were achieved in respectively 48 and 43% of cases. The main predictors of complete resolution of hypertension were absence of diabetes, low BMI, high plasma ARR and high ARS. Taking these factors into account may help identify patients at risk of persistent postoperative hypertension who may require long-term surveillance and medication.

Immunohistochemical staining seems mandatory for individualizing and shortening follow-up in unilateral primary aldosteronism.

The clinical significance of immunohistochemistry (IHC) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow-up of PA patients could be in sight. Long-term outcomes of patients, classified based on IHC, need further investigation. We aimed to assess long-term clinical outcomes for unilateral PA, classifying patients based on IHC. A nationwide observational study, with up to 16 years follow-up, executed in 2007-2016 at Landspitali University Hospital, tertiary referral center. Patients were diagnosed and treated in line with the current guidelines. Haematoxylin and eosin (H&E) tissue slides were stained using CYP11B1 and -B2 antibodies. All cases were re-evaluated and classified according to the HISTALDO consensus. Outcomes were assessed using the PASO criteria. All unilateral PA patients diagnosed in 2007-2016 in Iceland, 26 patients aged 28-73 years, who underwent adrenalectomy, were included. Aldosterone, renin, and cortisol values, use and dosage of antihypertensives, potassium supplementation, blood pressure and serum potassium pre-intervention and throughout follow-up, and histopathology results post-adrenalectomy. Following IHC, an aldosterone-producing nodule was seen in 12 adrenals, an aldosterone-producing adenoma in 10 and multiple aldosterone-producing micronodules in four. IHC altered histopathology from previous H&E diagnosis in 23% (6/26) of the patients. In total, 81% (21/26) of the patients had partial clinical success. Eight percent (2/26) of the patients needed potassium supplementation during follow-up. In the classical group, the AVS results were more determinative with significantly higher lateralization index (median 10.1 vs. 5.3, p = .04) and more contralateral suppression (median nondominant ratio 0.4 vs. 1.0, p = .03). One out of five patients with complete clinical success at 12 months post-op had severe relapse later, the other four were normotensive without antihypertensives for up to 10 years. We found IHC mandatory for accurate histopathologic diagnosis of PA. Our results support the importance of contralateral suppression when interpreting AVS results. Also, the study highlights the complicated assessment of clinical outcome and importance of aldosterone and renin measurements during follow-up.

Surgery for Primary Aldosteronism in France From 2010 to 2020 - Results from the French-Speaking Association of Endocrine Surgery (AFCE): Eurocrine Study Group.

Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020. Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers. Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database. Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs. These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse.

Adrenal Vein Sampling in the Young - Necessary or Not?

Current clinical guidelines from the US Endocrine Society state that adrenal venous sampling (AVS) may not be necessary in patients younger than 35 years with marked aldosteronism and a solitary adrenal adenoma on imaging. At the time when the guidelines were published, only one study supported the statement, a study that included 6 patients younger than 35 years, all of whom had unilateral adenoma on imaging and unilateral primary aldosteronism (PA), according to AVS. Since then, to our knowledge, four additional studies have been published that provide data on concordance between conventional imaging and AVS among patients younger than 35 years. In these studies, 7 of 66 patients with unilateral disease on imaging had bilateral disease, according to AVS. We find it, therefore, reasonable to conclude that imaging studies alone inaccurately predict laterality in a significant number of young patients with PA and that available data challenge the current clinical guidelines.

Diagnostic Accuracy of Adrenal Iodine-131 6-Beta-Iodomethyl-19-Norcholesterol Scintigraphy for the Subtyping of Primary Aldosteronism.

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. 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. 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]. 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.

Association of urinary liver-type fatty acid–binding protein with outcomes after adrenalectomy for unilateral primary aldosteronism

Background and AimsThis study explored the association between urinary liver-type fatty acid-binding protein to creatinine (uL-FABP-cre) ratio and postoperative clinical failure in unilateral primary aldosteronism (PA) patients undergoing adrenalectomy. Materials and MethodsData from the Taiwan Primary Aldosteronism Investigation Group database were analyzed, including patients with unilateral PA who had adrenalectomy between December 2015 and October 2018. Statistical methods included generalized additive modeling, logistic regression analysis, net reclassification improvement (NRI), and the C statistic. ResultsIn the study cohort of 131 patients (mean age 52.3 ± 10.8 years; 43.5% male), 117 achieved clinical success, while 14 experienced clinical failure. A uL-FABP-cre ratio ≥5 predicted clinical failure (odds ratio: 6.22, p = 0.005). Subgroup analysis revealed its efficacy in predicting clinical failure in patients with BMI ≥ 24 kg/m2, normokalemia, or <5 years of hypertension.Furthermore, incorporating uL-FABP-cre ratio into the Primary Aldosteronism Surgical Outcome (PASO) score significantly improved predictive ability. The addition increased the C statistic from 0.671 to 0.762 (p < 0.01) and improved category-free NRI by 0.675 (p = 0.014). ConclusionA uL-FABP-cre ratio ≥5 accurately predicted clinical failure post-adrenalectomy in unilateral PA, enhancing PASO score's identification of high-risk patients for postoperative clinical failure.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation. To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side and surgically cured unilateral primary aldosteronism, used as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined. We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55. With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results. URL: https://www. gov; Unique identifier: NCT01234220.

Optimizing adrenal vein sampling in primary aldosteronism subtyping through LC–MS/MS and secretion ratios of aldosterone, 18-oxocortisol, and 18-hydroxycortisol

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.

UNILATERALLY SELECTIVE ADRENAL VEIN SAMPLING FOR IDENTIFICATION OF SURGICALLY CURABLE PRIMARY ALDOSTERONISM

Objective: Adrenal venous sampling (AVS) is recommended for the identification of unilateral surgically curable primary aldosteronism (PA) but, owing to failed bilateral adrenal vein cannulation, is often clinically useless. Design and method: We investigated if only unilaterally selective AVS studies can allow identification of the responsible adrenal. Methods: Among 1625 patients consecutively submitted to AVS in tertiary referral centers, we selected those with a unilaterally selective AVS result and a final diagnosis of unilateral PA. Using the latter as gold reference, we examined the accuracy of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity. Results: The RASI values distribution showed prominent differences between patients with and without unilateral PA. The area under ROC curves (AUROC) was 0.714 and 0.855 for RASI values of the responsible and the contralateral side, respectively. While RASI values &gt;2.55 on the culprit side and less than 0.96 on the contralateral side furnished the highest accuracy for detection of surgically cured unilateral PA, only 20% and 16% had RASI values less than 0.96 and &gt;2.55, respectively, in the patients without unilateral PA. Conclusions: With the strength of the gold standard entailing an unambiguous diagnosis of unilateral PA and large real-life dataset, these results indicate the feasibility of identifying unilateral PA using unilaterally selective AVS results.

Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

CXCR4-DIRECTED [68GA]GA-PENTIXAFOR PET/CT AS A NOVEL DIAGNOSTIC MODALITY IN PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is caused by autonomous production of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction (‘subtyping’) is crucial, PA is cured by adrenalectomy in unilateral PA and is treated by medication in bilateral PA. Subtyping is currently done by adrenal vein sampling (AVS). We propose a new diagnostic imaging modality employing the PET-tracer [68Ga] Ga-PentixaFor. This tracer reportedly has high uptake in APAs, whereas uptake is low in BAH or normal adrenals. The goal of this study is to determine concordance of [68Ga] Ga-PentixaFor PET/CT and AVS. Secondary outcomes are optimal timepoint for scanning and quantitative criteria for lateralization at the optimal timepoint. Design and method: This study is step 1 of a two-step randomized controlled diagnostic trial. We included patients with PA from Radboudumc Nijmegen and UMC Utrecht, confirmed by an intravenous salt-loading test. Patients underwent AVS and [68Ga]Ga-PentixaFor PET/CT. A dynamic scan was performed to determine optimal timepoint for scanning in the first 6 patients. The main outcome was the concordance of AVS and [68Ga]Ga-PentixaFor PET/CT. The SUVmax was used to determine lateralization in [68Ga]Ga-PentixaFor PET/CT. Results: Nineteen patients underwent adrenal vein sampling and a [68Ga]Ga-PentixaFor PET/CT. The optimal timepoint of scanning was 1h post injection. AVS showed lateralization in 13/19 patients. Using a cut-off of SUV¬max-ratio of 1.4, concordance was 68%. (figure 1) Using a Bayesian prediction model, the predicted concordance is: 67% (CI80% = 53 - 79). Figure 1: Scatter dot plot of the SUVmax Ratio in patients who had lateralization or no lateralization on AVS with a cut-off value of 1.4. Conclusions: [68Ga]Ga-PentixaFor PET/CT is a new imaging modality with high concordance with AVS. It is safe, readily available and as an out-patient procedure has the potential to improve subtyping in PA. With these preliminary results we have sufficient evidence of concordance to proceed to step 2 of the two-step trial: A pragmatic randomized controlled diagnostic trial, in which patients will be randomized in either [68Ga]Ga-PentixaFor PET/CT or AVS.

The outcomes of transcatheter adrenal ablation in patients with primary aldosteronism: a systematic review and meta-analysis

BackgroundThe use of transcatheter adrenal ablation as an alternative treatment for primary aldosteronism (PA) patients remains a subject of debate, with outcomes varying widely across existing studies. This meta-analysis aims to evaluate the results of adrenal ablation and estimate the effectiveness and safety of this therapeutic approach.MethodsA comprehensive search was conducted across PubMed, Embase, and Cochrane Library databases for studies published up to October 2022. Outcomes analyzed included the combined clinical success rate, biochemical success rate, and complication rate, which were assessed using a random-effects model.ResultsFive studies, comprising 234 PA patients, were included in the analysis. The combined clinical success rate was 74% (95% CI: 69%-79%), and the biochemical success rate was 74% (95% CI: 53%-95%). Subgroup analysis revealed that the combined clinical success rate from Unilateral PA (72%, 95% CI: 46%-98%) was similar to the rate from Unilateral + Bilateral (73%, 95% CI: 52.0%-94.0%), while the clinical success rate of the PASO subgroup (78%, 95% CI: 66.0%-89.0%) was higher than the rate of other criteria (51%, 95% CI: 40.0%-63.0%). The combined complication rates were as follows: mild fever, 23% (95% CI: 12%-33%); back pain, 84% (95% CI: 77%-91%); and pleural effusion, 9% (95% CI: 0%-18%). All complications resolved within one week following the procedure. No late complications or ablation-related deaths were reported.ConclusionsTranscatheter adrenal ablation for PA patients is safe and demonstrates a relatively high clinical success rate. Presently, this approach is suitable for PA patients who are unwilling to undergo surgery or receive long-term mineralocorticoid receptor antagonist (MRA) treatment.Systematic Review registrationINPLASY, identifier 2022110076

Diagnostic accuracy of using multiple cytokines to predict aldosterone-producing adenoma

Here, we aimed to study the important cytokines in plasma to identify the aldosterone-producing adenoma (APA). 19 unilateral primary aldosteronism (UPA) patients and 19 healthy people were divided into UPA group and Control group, and the serum of bilateral adrenal veins and inferior vena cava collected by adrenal blood sampling (AVS) in UPA patients and the serum from the healthy subjects were all used to detect multiple cytokines by Luminex immunoassays. Additionally, The UPA patients subjected to laparoscopic adrenalectomy were divided into different groups by pathological results for further study. According our results, IP-10, CXCL9 and RANTES were significantly higher in UPA group compared with control group, and the combination of the three cytokines have significant predictive power for predicting UPA, while the correlational analyses demonstrated that IP-10 and CXCL9 were positively correlated with BP and HR, while EGF was positively correlated with HDL. Additionally, IL-1b was suggested to be the most potential diagnostic biomarker to discriminate the APA and unilateral adrenal hyperplasia (UAH). The present findings might suggest a possibility of IP-10, CXCL9 and RANTES served as a sign to help UPA diagnosis and finally used to assist the diagnosis of APA, while IL-1b was suggested to be the most potential diagnostic biomarker to identify the APA from the UAH patients.