[Off-pump Resection of Dopamine-secreting Cardiac Paraganglioma].

Dopamine-secreting paragangliomas is known to be rare. The average annual incidence rate was reported 0.8 per 100,000 person-years. Approximately 1 to 2% of paragangliomas occur in the chest. We describe a patient with a large dopamine-secreting cardiac paraganglioma, right adrenal tumor and carotid body tumor. A 26-year-old man with progressive exertional dyspnea was referred to our hospital for further management of multiple paragangliomas. Positron emission tomography (PET) and PET-computed tomography (CT) detected those three legions. The diameter of cardiac paraganglioma was over 45 mm and was biggest among three tumors. Firstly, therefore, we planned cardiac paraganglioma resection. Through left lateral thoracotomy in the 4th intercostal space via, cardiac paraganglioma was resected under cardiopulmonary bypass and beating heart. Postoperative course was uneventful. Tumor cells were positive for synaptophysin and chromogranin A. Free metanephrines in the serum and urinary fractionated metanephrines normalized after cardiac surgery while the other two tumors remained untreated.

Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism.

The new Japanese guidelines for primary aldosteronism introduce a category in the judgment of functional confirmatory tests that is called the "borderline range," which is rare in the other international guidelines. The clinical characteristics of this borderline group are not yet understood. To investigate whether this borderline group has any significant differences in terms of target organ damage, we used data from a Japanese nationwide registry (JPAS-II) of individuals with primary aldosteronism or essential hypertension to compare the borderline group with the definitive-positive group and the negative group. We analyzed the cases of 1785 patients based on their captopril-challenge test results. Since the JPAS-II database contains plasma aldosterone concentration values obtained based on both radioimmunoassay (n = 1555) and chemiluminescent enzyme immunoassay (n = 230) principles, we converted these values to their equivalents as if measured by chemiluminescent enzyme immunoassay and conducted all analyses under the simulated condition. Multicovariate-adjusted models revealed significant prevalance odds ratios for chronic kidney disease (2.01, 95% confidence interval: 1.13 to 3.61), electrocardiographic abnormalities (1.66, 95% confidence interval: 1.16 to 2.37). No significant difference was observed between the borderline and negative groups in these assessments (odds ratio [95% confidence interval] for chronic kidney disease: 0.73 [0.26 to 2.02] and electrocardiographic abnormalities: 1.01 [0.60 to 1.70]). We confirmed that the prevalence of target organ damage increases linearly as the aldosterone-to-renin ratio rises following the captopril challenge test. These results provide material to consider regarding the significance of the provisionally established borderline group.

Predictor of Steroid Replacement Duration after Removal of Cortisol-producing Adenoma.

Objective Cortisol-producing adenoma (CPA) is a major subtype of functional adrenal tumors. CPAs are generally treated with adrenalectomy; however, it is difficult to predict the ideal duration of glucocorticoid replacement after resection. This study explored pre-operative factors predictive of glucocorticoid replacement therapy duration after CPA resection. Mehtods This multicenter retrospective observational study was conducted as part of the Advancing Care and Pathogenesis of Intractable Adrenal Diseases in Japan (ACPA-J) from January 2006 to December 2015. Patients This study was conducted at 10 referral centers and included 124 patients who received hydrocortisone replacement therapy after adrenalectomy for CPA. Results The median duration of replacement therapy was 12 (interquartile range, 5-24) months. In the single regression analysis, the sex (P=0.04), morning ACTH level (P=0.02), morning serum cortisol level (P=0.003), midnight serum cortisol level (P<0.001), serum cortisol level after a 1-mg dexamethasone suppression test (P<0.001), presence of lumbar compression fracture (P=0.015), and Cushingoid appearance (P<0.001) were all significantly associated with the replacement therapy duration. In multiple regression analyses, the midnight serum cortisol level and presence of lumbar compression fracture were significantly correlated with the replacement therapy duration after adjusting for other parameters. Conclusion Our results suggest that high midnight serum cortisol levels, which cause persistent suppression of the HPA axis, contribute to a delay in HPA axis recovery. Lumbar compression fracture is an important symptom that reflects the severity and persistence of cortisol secretion.

Prevalence of unilateral hyperaldosteronism in primary aldosteronism: impact of a novel chemiluminescent immunoassay for measuring plasma aldosterone in Japan.

This study aims to evaluate the prevalence of unilateral hyperaldosteronism (UHA) and its clinical characteristics in patients with primary aldosteronism (PA), diagnosed using plasma aldosterone concentration (PAC) measured by chemiluminescent enzyme immunoassay (CLEIA). We retrospectively analyzed data of 199 PA patients from the Japan Primary Aldosteronism Study II (JPAS II) dataset, including patients who underwent adrenal venous sampling (AVS) and the captopril challenge test (CCT) and/or saline infusion test (SIT), with PAC measured by CLEIA. We focused on two categories: confirmed PA, where patients exhibit clear biochemical evidence of the disorder, and borderline PA, where patients present with marginal biochemical indicators, as outlined in the Japan Endocrine Society's clinical practice guideline for the diagnosis and management of PA. In confirmed PA cases, over the half of patients was UHA, while approximately 15 to 20% of borderline cases were found to be UHA. The prevalence of hypokalemia was identified as predictor of UHA among borderline cases. Among borderline cases with no hypokalemia and adrenal nodules on CT imaging, only 6 to 8% of patients were found to have UHA. Notably, some patients exhibited UHA despite negative results on one test but confirmed result on the other, particularly those with hypokalemia or adrenal nodules on CT imaging. In conclusion, the findings validate the importance of AVS in confirmed PA cases and the need for careful assessment in borderline cases. When feasible, conducting both CCT and SIT, and interpreting their results alongside other clinical indicators, could provide a more comprehensive assessment.

Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism.

BACKGROUND: Clinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure. METHODS: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation. The establishment of optimal cut-offs was informed by a survey of 82 PA patients in Japan, aimed at determining the LI cut-off aligned with patient expectations for a surgical cure rate. RESULTS: The survey revealed that a median cure rate expectation of 80% would motivate PA patients towards undergoing adrenalectomy. The optimal LI cut-offs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on CT imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cut-offs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found. CONCLUSIONS AND RELEVANCE: The present study clarified the optimal LI cut-offs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.

Primary aldosteronism patients with previous cardiovascular and cerebrovascular events have high aldosterone responsiveness to ACTH stimulation.

Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and ß-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

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

BACKGROUND: 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. OBJECTIVES: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. METHODS: 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; we used surgically cured unilateral primary aldosteronism 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. RESULTS: 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. CONCLUSIONS: 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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01234220.

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.

International multicenter survey on screening and confirmatory testing in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

Impact of a change to a novel chemiluminescent immunoassay for measuring plasma aldosterone on the diagnosis of primary aldosteronism.

In Japan, the standard method for measuring plasma aldosterone concentration (PAC) for primary aldosteronism (PA) diagnosis was changed from radioimmunoassay (RIA) to a novel chemiluminescent enzyme immunoassay (CLEIA). The purpose of this study is to simulate the possible impact of the change on PA diagnosis. This retrospective study assessed 2,289 PA patients. PACs measured by conventional RIA were transformed to estimated PACs (CLEIA) as follows: RIA (pg/mL) = 1.174 × CLEIA (pg/mL) + 42.3. We applied the estimated PAC (CLEIA) to the conventional cut-off of aldosterone-to-renin activity ratio ≥200 for screening and captopril challenge test (CCT) and PAC ≥60 pg/mL for saline infusion test (SIT). Application of the estimated PAC to screening and confirmatory tests decreased the number of PA diagnoses by 36% (743/2,065) on CCT and 52% (578/1,104) on SIT (discrepant cases). Among the discrepant cases, 87% (548/628) of CCT and 87% (452/522) of SIT were bilateral on adrenal venous sampling (AVS). Surgically treatable aldosterone-producing adenomas (APAs) were observed in 6% (36/579) and 5% (23/472) of discrepant cases on CCT and SIT, respectively; most were characterized by hypokalemia and/or adrenal nodule on CT imaging. Application of the PAC measured by the novel CLEIA to conventional cut-offs decreases the number of PA diagnoses. Although most discrepant cases were bilateral on AVS, there are some APA cases that were characterized by hypokalemia and/or adrenal tumor on CT. Further studies which evaluate PACs measured by both RIA and CLEIA for each patient are needed to identify new cut-offs for PAC measured by CLEIA.

A hyperaldosteronism subtypes predictive model using ensemble learning.

This study aimed to develop a machine-learning algorithm to diagnose aldosterone-producing adenoma (APA) for predicting APA probabilities. A retrospective cross-sectional analysis of the Japan Rare/Intractable Adrenal Diseases Study dataset was performed using the nationwide PA registry in Japan comprised of 41 centers. Patients treated between January 2006 and December 2019 were included. Forty-six features at screening and 13 features at confirmatory test were used for model development to calculate APA probability. Seven machine-learning programs were combined to develop the ensemble-learning model (ELM), which was externally validated. The strongest predictive factors for APA were serum potassium (s-K) at first visit, s-K after medication, plasma aldosterone concentration, aldosterone-to-renin ratio, and potassium supplementation dose. The average performance of the screening model had an AUC of 0.899; the confirmatory test model had an AUC of 0.913. In the external validation, the AUC was 0.964 in the screening model using an APA probability of 0.17. The clinical findings at screening predicted the diagnosis of APA with high accuracy. This novel algorithm can support the PA practice in primary care settings and prevent potentially curable APA patients from falling outside the PA diagnostic flowchart.

Associated factors and effects of comorbid atrial fibrillation in hypertensive patients due to primary aldosteronism.

The incidence of atrial fibrillation (AF) and risk of cardiovascular events are reportedly higher in patients with primary aldosteronism (PA) than essential hypertension. However, associated factors of comorbid AF and cardiovascular events in PA patients after PA treatment remain unclear. This nationwide registration study included PA patients ≥20 years old. Incident cardiovascular events were observed with a mean follow-up of approximately 3 years. A total of 3654 patients with PA were included at the time of analysis. Prevalence of AF was 2.4%. PA patients with AF were older, more frequently male and had longer duration of hypertension than those without AF. No significant difference in basal plasma and adrenal venous aldosterone concentration, renin activity, potassium concentration, confirmatory tests of PA, laterality or surgery rate were seen between groups. Logistic regression analysis showed age, male sex, cardiothoracic ratio, past history of coronary artery disease and heart failure were independent factors associated with AF. PA patients with AF showed a higher frequency of cardiovascular events than those without AF (P < 0.001). Multivariate Cox analyses demonstrated AF in addition to older age, duration of hypertension, body mass index and chronic kidney disease as independent prognostic factors for cardiovascular events after PA treatment. Incidence of cardiovascular events were significantly lower in PA patients with AF than AF patients from the Fushimi registry during follow-up after adjusting age, sex and systolic blood pressure. Early diagnosis of PA may prevent AF and other cardiovascular events in PA patients by shortening the duration of hypertension and appropriate PA treatment.

Heterogeneous circulating miRNA profiles of PBMAH.

Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA). Methods: miRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR. Results: PBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma (P = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma (P = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma. Conclusion: Circulating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH.

Effect of Intraprocedural Cortisol Measurement on ACTH-stimulated Adrenal Vein Sampling in Primary Aldosteronism.

Context: Adrenocorticotropin (ACTH) loading is used to increase the success rate of adrenal vein sampling (AVS). Objective: We aimed to determine the effect of intraprocedural cortisol measurement (ICM) on ACTH-stimulated AVS (AS-AVS) owing to a lack of reliable data on this topic. Methods: This multicenter, retrospective, observational study took place in 28 tertiary centers in Japan. Among 4057 patients enrolled, 2396 received both basal AVS (B-AVS) and AS-AVS and were divided into 2 groups according to whether ICM was used. The effect of ICM on AS-AVS was measured. Results: In patients who underwent both AVS procedures, the ICM group had significantly higher success rates for both B-AVS and AS-AVS than the non-ICM group did. However, the probability of failure of AS-AVS after a successful B-AVS and the probability of success of AS-AVS after a failed B-AVS were not significantly different in the 2 groups. For subtype diagnosis, propensity-score matching revealed no significant difference between the 2 groups, and the discrepancy rate between B-AVS and AS-AVS for subtype diagnosis was also not significantly different. Conclusion: ICM significantly increased the success rate of B-AVS and AS-AVS in protocols in which both AVS procedures were performed and had no effect on subtype diagnosis. However, in protocols in which both AVS procedures were performed, the results suggest ICM may not be necessary when performing AS-AVS if ICM is used only when B-AVS is performed. Our study suggests that ICM during AVS plays an important role and should be recommended.

The metabolic phenotype of patients with primary aldosteronism: impact of subtype and sex - a multicenter-study of 3566 Caucasian and Asian subjects.

Background: Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics. Methods: We conducted a retrospective multicenter study including 3566 patients with APA or IHA of Caucasian and Asian origin. We compared the prevalence of metabolic disorders between APA and IHA patients at the time of diagnosis and 1-year post-intervention, with special references to sex differences. Furthermore, correlations between metabolic parameters and plasma aldosterone, renin, or plasma cortisol levels after 1 mg dexamethasone (DST) were performed. Results: As expected, APA patients were characterized by higher plasma aldosterone and lower serum potassium levels. Only female IHA patients demonstrated significantly worse metabolic parameters than age-matched female APA patients, which were associated with lower cortisol levels upon DST. One-year post-intervention, female adrenalectomized patients showed deterioration of their lipid profile, when compared to patients treated with mineralocorticoid receptor antagonists. Plasma aldosterone levels negatively correlated with the BMI only in APA patients. Conclusions: Metabolic alterations appear more prominent in women with IHA. Although IHA patients have worse metabolic profiles, a correlation with cortisol autonomy is documented only in APAs, suggesting an uncoupling of cortisol action from metabolic traits in IHA patients.

Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism.

A recent report stated that patients with primary aldosteronism who remain renin suppressed during mineralocorticoid receptor antagonist treatment might have a higher risk of developing cardiovascular disease than those with unsuppressed renin activity. We retrospectively investigated the incidence of composite cardiovascular disease and risk factors for cardiovascular disease in 1115 Japanese patients with primary aldosteronism treated with mineralocorticoid receptor antagonists. The median follow-up period was 3.0 years, and the incidence of cardiovascular events was very low (2.1%) throughout 5 years of follow-up. Changes in plasma renin activity from before to after mineralocorticoid receptor antagonist treatment were divided into three groups based on tertile, low, intermediate, and high plasma renin activity change groups, with incidences of cardiovascular disease events of 2.1%, 0.5%, and 3.7%, respectively. Multivariate Cox regression analysis revealed age (adjusted hazard ratio, 1.07; 95% confidence interval, [1.02-1.12]) and body mass index (adjusted hazard ratio, 1.13 [1.04-1.23]) as independent risk factors for cardiovascular disease. The high plasma renin activity change group had significantly higher cardiovascular disease risk with mineralocorticoid receptor antagonist treatment than the intermediate plasma renin activity change group (adjusted hazard ratio, 5.71 [1.28-25.5]). These data suggest that a high change in renin level after mineralocorticoid receptor antagonist treatment may not necessarily predict a better prognosis of cardiovascular disease in patients with primary aldosteronism.