Clinical value of 68Ga-pentixafor PET/CT in patients with primary aldosteronism and bilateral lesions: preliminary results of a single-centre study.

BACKGROUND: Subtype diagnosis of primary aldosteronism (PA) is used to determine treatment, and the potential utility of 68Ga-pentixafor PET/CT for investigation of PA has long been recognized. The study aimed to evaluate the clinical value of 68Ga-pentixafor PET/CT in the diagnosis and prognosis of patients with bilateral lesions identified by CT. METHODS: In total, 25 patients with PA and bilateral lesions on CT were retrospectively evaluated. All patients underwent 68Ga-Pentixafor PET/CT and adrenal vein sampling. The analysis focused on establishing the relationship between bilateral adrenal lesions SUVmax and the ratio of bilateral adrenal lesions SUVmax (CON) and clinical diagnosis, treatment outcomes, and KCNJ5 gene status. RESULTS: The concordance rate between 68Ga-Pentixafor PET/CT and adrenal venous sampling was 65.2% (15/23). The lateralization results of 68Ga-pentixafor PET/CT supported the clinical decisions of 20 patients with PA, 90% of whom showed effectiveness in treatment. The SUVmax on the dominant side of the surgically treated patients was higher than that of patients treated with drugs. The SUVmax of the KCNJ5 mutant group was higher than that of the KCNJ5 wild group, and 68Ga-Pentixafor uptake was correlated with KCNJ5 gene status. CONCLUSIONS: 68Ga-Pentixafor PET/CT proves beneficial for patients with PA with bilateral lesions on CT. The treatment is generally effective based on the results of PET lateralization. Simultaneously, a certain relationship exists between 68Ga-Pentixafor PET/CT and KCNJ5 gene status, warranting further analysis.

Sparing confirmatory testing in primary aldosteronism (SCIPA): a multicenter retrospective diagnostic accuracy study.

BACKGROUND: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. METHODS: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. RESULTS: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 - 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) CONCLUSION: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing. PROTOCOL REGISTRATION NUMBER: SRCTN34186253.

Relation between blood pressure time in range and composite cardiovascular outcomes in patients with primary aldosteronism: a retrospective case study.

PURPOSE: To investigate the association between blood pressure (BP) time in range (TIR) and composite cardiovascular outcomes in patients with primary aldosteronism (PA). METHODS: Between January 2019 and December 2021, 47 patients with PA were recruited from the First Affiliated Hospital of Xiamen University. Twenty-four-hour ambulatory BP monitoring (ABPM) and cardiovascular outcomes were assessed in all patients during the first diagnosis of PA. RESULTS: The mean age of the patients was 48.8 ± 11.4 years. Compared to PA without composite cardiovascular outcomes, the nighttime systolic BP TIR [31.2% (6.2%, 81.2%) vs. 11.5% (0.0%, 29.7%), p = 0.02] and defined daily dose (DDDs) of antihypertensive medication [2.0 (1.0, 2.8) vs. 1.0 (1.0, 2.0), p = 0.03] were lower in PA patients with composite cardiovascular outcomes, while higher glucose (5.0 ± 1.0 mmol/L vs. 5.9 ± 1.5 mmol/L) and prevalence of a history of alcohol intake was higher in PA patients with composite cardiovascular outcomes. There were no differences in age, sex, BMI, smoking, duration of hypertension, lipid levels, aldosteronism, clinic BP, 24-hour mean BP, daytime or nighttime BP, percentage of nocturnal SBP or DBP decline, 24-hour BP TIR, daytime BP TIR, or nighttime DBP TIR between the two groups. After adjusting for confounding factors, nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes (adjusted OR = 0.92 [95% CI 0.86, 0.99]) in multiple logistic regression analysis. CONCLUSION: Nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes in patients with PA.

Evaluation and Management of Resistant Hypertension: Core Curriculum 2024.

Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research.

Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard.

BACKGROUND: Captopril challenge test (CCT), seated saline infusion test (SSIT), oral sodium loading test (OSLT) and fludrocortisone suppression test (FST) are widely used diagnostic tests for primary aldosteronism (PA). These tests differ in terms of safety and complexity. Whether the simpler tests (CCT and SSIT) are comparable in diagnostic performance to the more complex ones (FST and OSLT) is unclear. PURPOSE: To compare the diagnostic accuracy of the four tests. METHODS: This is a retrospective study of hypertensive patients who were screened for PA and completed at least one confirmatory test. The patients were divided into two cohorts: one including those who completed one to three tests was used for the estimation of sensitivity and specificity. The other including those who completed four tests was used for the comparison of accuracy. Bayesian method was used to obtain the sensitivity, specificity, and Youden index of each test. RESULTS: The study included 1011 hypertensive patients. Among them, 895 patients completed one to three tests (including 889 CCT, 605 FST, 611 SSIT and 69 OSLT), and 116 patients completed four tests. SSIT had the highest sensitivity of 0.82(95% CI 0.78-0.86) but the lowest specificity of 0.76(0.70-0.80). OSLT had the lowest sensitivity of 0.65(0.56-0.75) but the highest specificity of 0.91(0.82-0.96). The sensitivity and specificity were 0.78 (95% CI, 0.75-0.82), 0.82 (95% CI, 0.78-0.85), for CCT, and 0.77 (95% CI, 0.73-0.81), 0.87 (95% CI, 0.82-0.91) for FST, respectively. The Youden index was not significantly different among the four tests[0.60(0.55-0.65) for CCT; 0.58(0.51-0.64) for SSIT; (0.64(0.57-0.69) for FST; 0.56(0.43-0.67) for OSLT]. CONCLUSION: The accuracy of simpler tests is comparable to the more complex ones. Considering the safety and simplicity of CCT, it may be a reasonable first choice when confirming the diagnosis of PA.

Efficacy and safety of adrenal arterial embolization for primary aldosteronism: a systematic review and meta-analysis.

Background: Primary aldosteronism (PA) is related with resistant hypertension and cardiovascular events. Adrenal artery embolization (AAE) is a choice for patients who refused surgery and medical therapy. However, whether AAE can effectively and safely treat PA is unclear. We performed this meta-analysis to determine the efficacy and safety of AAE for patients with PA. Methods: Databases including Cochrane Library, Embase, PubMed and Web of Science were used to obtain relevant articles published before July 30, 2023. The primary outcome was blood pressure before and after AAE. The second outcomes included changes in plasma aldosterone level, serum potassium level, and plasma cortisol level. Results: Finally, 7 prospective studies with 222 patients were included. The results showed that systolic and diastolic blood pressure was reduced by 21.68 mmHg (P<0.001) and 10.54 mmHg (P=0.007) respectively after AAE. The change in plasma aldosterone and serum potassium level was -11.52 ng/dL and 0.61 mmol/L respectively (P<0.001), whereas the reduction in cortisol level was not apparent. Moreover, AAE is a relatively safe procedure which only causes some minor complications such as back pain and fever. Conclusions: This meta-analysis indicated that AAE could effectively and safely treat PA. It is a good choice for patients that are not suitable for adrenalectomy or drug therapy.

Targeted treatment reverses increased left cardiac work in unilateral versus bilateral primary aldosteronism.

BACKGROUND: The incidence of cardiovascular complications may be higher in unilateral than in bilateral primary aldosteronism (PA). We compared non-invasive hemodynamics before and after targeted therapy of bilateral versus unilateral PA. METHODS: Adrenal vein sampling was performed, and cardiovascular variables were recorded using radial artery pulse wave analysis and whole-body impedance cardiography (n=114). In a subset of 40 patients (adrenalectomy n=20, spironolactone-based treatment n=20), hemodynamic recordings were again performed after 33 months of targeted PA treatment. RESULTS: In initial cross-sectional analysis, 51 patients had bilateral and 63 had unilateral PA. The mean ages were 50.6 and 54.3 years (p=0.081), and body mass indexes were 30.3 and 30.6 kg/m2 (p=0.724), respectively. Aortic blood pressure and cardiac output did not significantly differ between the groups, but evaluated left cardiac work was ~10% higher in unilateral PA (p=0.022). In the followup study, initial and final blood pressure levels in the aorta were not significantly different, while initial cardiac output (+13%, p=0.015) and left cardiac work (+17%, p=0.009) were higher in unilateral than in bilateral PA. After a median treatment time of 33 months, the differences in cardiac load were abolished, and extracellular water volume was reduced by 1.3 and 1.4 liters in bilateral versus unilateral PA, respectively (p=0.814). CONCLUSIONS: These results suggest that unilateral PA burdens the heart more than bilateral PA, providing a possible explanation for the higher incidence of cardiac complications in unilateral disease. A similar reduction in aldosterone-induced volume excess was obtained with targeted surgical and medical treatment of PA.

Adrenocortical Tumor Associated With Pathogenic Variant in KCNJ5 and DNA Methylation of CYP11B2 in Primary Aldosteronism.

Primary aldosteronism (PA) is a subtype of secondary hypertension categorized as either unilateral PA (eg, aldosterone-producing adenoma [APA]) or bilateral PA. CYP11B2, an aldosterone synthase, is highly expressed in APA. Recent studies have revealed a high prevalence of pathogenic variants in KCNJ5 and the role of DNA methylation on CYP11B2 in APA. We present a case of unilateral PA with pathogenic variants in KCNJ5 and suppressed CYP11B2 expression. A 55-year-old woman with hypertension was referred to our hospital. A high aldosterone-renin ratio was observed; PA was confirmed using the captopril challenge test and the furosemide upright test. Although computed tomography showed no evident tumors in either adrenal gland, adrenal vein sampling revealed left gland dominance. Postoperatively, the aldosterone-renin ratio decreased and captopril challenge test showed negative findings. Pathogenic variants in the KCNJ5 were detected in the adenoma. Although immunohistochemistry for CYP11B2 was negative in adenoma, an aldosterone-producing cell cluster was confirmed in the adjacent left adrenal gland. Furthermore, DNA methylation analysis of the adenoma indicated hypermethylation in the CYP11B2 promoter region. The pathogenic variant in KCNJ5, specific to APA, induces CYP11B2 overexpression, resulting in excess aldosterone. However, these effects can be suppressed by DNA methylation.

The prevalence of metabolic syndrome in primary aldosteronism and essential hypertension: A systematic review and meta-analysis.

It remained debates on metabolic-related disorders in patients with primary aldosteronism (PA) and essential hypertension (EH). A systematic review and meta-analysis was conducted to explore the prevalence of metabolic syndrome (MS) and the related indicators in PA and EH. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their commencement to December 2023 were searched for eligible studies. The meta-analysis was performed by Review Manager 5.3 and STATA 15.1 software. A total of 12 studies were included, revealing that there was no significant difference between PA and EH in the prevalence of MS (1.27[0.92, 1.76], p = 0.14) with higher heterogeneity (I2 = 68%, p = 0.0002), while it became significant different (1.45[1.17, 1.81], p = 0.0008) and lower heterogeneity (I2 = 26%, p = 0.19) in patients who were overweight or obese by subgroup analysis. Higher systolic blood pressure (2.99[0.67, 5.31], p = 0.01; I2 = 43%, p = 0.06) and diastolic blood pressure (2.10[0.82, 3.38], p = 0.001; I2 = 36%, p = 0.11) with lower heterogeneity, and lower triglyceride in PA group with higher heterogeneity (-0.23[-0.37, -0.09], p = 0.001; I2 = 76%, p < 0.0001) were observed. No significant difference was found in other indicators. This study showed a higher prevalence of MS in patients who were overweight or obese with PA. However, it was not the same in these patients who were in normal weight. More researches were needed to explore the relationship between PA and metabolism of glucose and lipid.

Clinical characteristics of primary aldosteronism screened from Chinese patients with hypertension: The China primary aldosteronism prospective study.

We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone-to-renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non-diagnosed PA (n = 147) were 4.54 (95% CI: 2.78-7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64-0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63-3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90-4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20-2.86) for a 0.3 mmol/l higher serum high-density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

The Prevalence of Obstructive Sleep Apnea in Patients With Primary Aldosteronism.

CONTEXT: Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation. OBJECTIVE: This work aimed to evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals. METHODS: An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters. RESULTS: Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P < .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction < .01). Among hypertensive OSA patients, 11.2% had PA. CONCLUSION: A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration.

Establishment of a scoring model for predicting clinical outcomes in patients with unilateral primary aldosteronism after superselective adrenal artery embolization.

OBJECTIVE: Superselective adrenal arterial embolization (SAAE) is a potential alternative treatment for patients with unilateral primary aldosteronism (PA) who refuse unilateral adrenalectomy. Therefore, we aimed to establish a scoring model to differentiate between hypertensive remission after SAAE. METHODS: This prospective cohort study involved 240 patients who underwent SAAE for unilateral PA. Patients were randomly divided into a model training set and a validation set at a ratio of 7:3. The clinical outcome was a response to hypertension remission, defined as complete, partial, or absent success at 6 months after SAAE. Multivariate logistic regression was performed to identify independent parameters and develop a nomogram to predict clinical outcomes after SAAE. The discrimination, calibration efficacy, and clinical utility of the predictive model were assessed. RESULTS: Five independent predictors were identified: female sex, duration of hypertension, defined daily dose of antihypertensive medication, diabetes, and target organ damage. The above five independent predictors were put into a predictive model that was presented as a nomogram. Using bootstrapping for internal validation, the C-statistic for the predictive model was 0.866 (95% confidence interval [CI]: 0.834 to 0.898). In the validation cohort, the area under the curve (AUC) of the nomogram for predicting hypertension remission after SAAE was 0.809. CONCLUSION: The present model is the first nomogram-based score that specifically predicts hypertension remission after SAAE in patients with unilateral PA using conventional parameters. This is an effective risk stratification tool that can be used by clinicians for timely and tailored preoperative risk discussions.

Surgical Management of Primary Aldosteronism.

Hypertension leads to multiple comorbidities and increased risk for mortality. Endocrine disorders contribute to the development of hypertension, including primary aldosteronism (PA). This article discusses the evaluation and management of PA.

68Ga-pentixafor PET/CT in the localization diagnosis of primary aldosteronism concurrent subclinical cushing's syndrsome: two case reports.

PURPOSE: Adrenal venous sampling (AVS) is recommended for subtyping primary aldosteronism (PA). However, in cases of PA, concurrent subclinical Cushing's syndrome (SCS) has the potential to confound AVS results. Pentixafor, a CXC chemokine receptor type 4-specific ligand, has been reported as a promising marker to evaluate functional nature of adrenal adenomas. This study aims to investigate the clinical value of Gallium-68 Pentixafor Positron Emission Tomography-Computed Tomography (68Ga-Pentixafor PET/CT) in the localization diagnosis of patients with PA plus SCS. METHODS: Two patients with a confirmed diagnosis of PA plus SCS underwent AVS and 68Ga-Pentixafor PET/CT. RESULTS: AVS results revealed no lateralization for both patients while 68Ga-Pentixafor PET/CT showed a unilateral adrenal nodule with increased uptake of 68Ga-Pentixafor. Unilateral adrenalectomy was performed based on the results of 68Ga-Pentixafor PET/CT. Subsequently, complete biochemical remission of autonomous aldosterone and cortisol secretion were achieved in both cases. CONCLUSIONS: 68Ga-Pentixafor PET/CT shows promising potential for the localization of aldosterone and cortisol co-secreting adrenal adenoma in patients with PA plus SCS.

Screening for primary aldosteronism in primary care: a scoping review.

BACKGROUND: Primary aldosteronism (PA) is the most common treatable and potentially curable cause of secondary hypertension. Prompt diagnosis and management by primary care physicians (PCPs) is important given the increased risk of cardiovascular complications however screening rates are low in primary care. Our aim was to identify factors that influence screening behaviour for PA among PCPs. METHOD: A rigorous scoping review of seven databases between 16/08/22 and 09/08/23 was used to investigate PA screening practices. Articles written in English from peer-reviewed literature within the last 20 years were eligible for inclusion if an aspect of their study was conducted in primary care. RESULTS: A total of 1380 titles and abstracts, and 61 full texts were screened, with 20 studies selected for data extraction. We identified three broad categories of factors influencing screening by PCPs-the patient, the clinician, and the healthcare system. Some studies targeted these factors to improve screening rates although there is little data on implementation and outcomes. CONCLUSION: Low awareness, inadequate guidelines, and poor access to testing were identified as key barriers to PA screening. Targeted education sessions for PCPs, clear guidelines, and closer proximity to diagnostic centres may be required to improve PA detection in primary care.

Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.

CONTEXT: The search for somatic mutations in adrenals resected from primary aldosteronism (PA) patients is being performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas. OBJECTIVE: To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next generation sequencing (NGS). METHODS: We investigated 127 consecutive adrenal aldosterone producing adenoma from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, Sanger sequencing and NGS. RESULTS: Double IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (χ2=22.492, p<0.001). CONCLUSIONS: NGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of APA patient.

Impact of the transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for the measurement of plasma aldosterone concentration (PAC) on the diagnosis of primary aldosteronism (PA) via retrospective analyses in Okinawa, Japan.

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

Evaluation of adrenal vein anatomy by adrenal venous sampling in patients with primary aldosteronism in Chinese.

Accurate cannulation of the adrenal vein is challenging during adrenal venous sampling (AVS) because of the variations in adrenal vein anatomy. This study aimed to investigate the adrenal venous morphology in Chinese and improve the success rate of AVS. A total of 221 participants with primary aldosteronism (PA) who underwent AVS were enrolled. Compare the morphology among subgroups divided according to sex, body mass index (BMI), and with or without adenoma. The success rate of right, left, and bilateral AVS was 98.60%, 97.20%, and 96.85%, respectively. The triangular pattern was the most common (39.37%) on the right side, while the glandlike pattern (70.14%) on the left. The proportion of adrenal venous morphology varies among patients with different sexecs (χ2 = 21.335, P < .001), BMI (χ2 = 10.642 P = .031), and with or without adenoma (χ2 = 10.637, P = .031) on the right side, and the male, obese and adenoma group showed a higher proportion of glandlike pattern than triangular pattern. If only dependent on computed tomography, 9.05% of patients incorrectly diagnose the dominant side, 14.48% of patients would have inappropriate surgery meanwhile 25.34% of patients would miss the surgical opportunity. In conclusion, the most common types of right and left adrenal venous morphology were triangular pattern and glandlike pattern, respectively. Sex, BMI, and the presence of adenoma affected right adrenal venous morphology. Adequate knowledge of the adrenal venous morphology is critical for improving the success rate of AVS and making an appropriate treatment for PA.