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2.
Front Endocrinol (Lausanne) ; 15: 1373862, 2024.
Article in English | MEDLINE | ID: mdl-38808106

ABSTRACT

Background: Previous studies have suggested that aldosterone may play a major role in calcium-phosphorus homeostasis and bone metabolism. However, the relationship between plasma aldosterone concentrations (PAC) and bone mineral density (BMD) in middle-aged and elderly hypertensive patients remains unclear. Therefore, this study sought to investigate the relationship between PAC levels and BMD and explore PAC's potential impact on osteoporosis and future fracture risk in hypertensive patients. Methods: Our study included a total of 1430 participants. Associations are tested using multiple linear and logistic regression models. Nonlinearity was investigated using the restricted cubic spline (RCS). We also performed mediating analyses to assess mediating factors mediating the relationship between PAC and osteoporosis. Results: The multiple linear regression showed a negative correlation between PAC and BMD and was generally positively associated with FRAX scores. Meanwhile, logistic regression analyses indicated that osteoporosis was highly correlated with PAC levels. In addition, a clear non-linear dose-response relationship was also shown in the constructed RCS model. Finally, mediation analyses showed that serum potassium played an important role in the development of osteoporosis. Conclusion: This study demonstrates that elevated PAC levels are strongly associated with decreased BMD, increased prevalence of osteoporosis, and the risk of future fractures in middle-aged and elderly hypertensive patients. Further studies are needed to confirm this relationship and reveal its underlying mechanisms.


Subject(s)
Aldosterone , Bone Density , Hypertension , Osteoporosis , Humans , Female , Middle Aged , Male , Aged , Hypertension/blood , Hypertension/epidemiology , Hypertension/complications , Osteoporosis/blood , Osteoporosis/epidemiology , Aldosterone/blood , Risk Factors , Fractures, Bone/blood , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Osteoporotic Fractures/blood , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Cross-Sectional Studies
3.
BMC Public Health ; 24(1): 1370, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38773424

ABSTRACT

BACKGROUND: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. METHODS: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. RESULTS: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. CONCLUSION: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.


Subject(s)
Aldosterone , Life Style , Humans , Male , Female , Cross-Sectional Studies , Middle Aged , Aldosterone/blood , Adult , China/epidemiology , Sex Factors , Aged , Obesity/blood , Obesity/epidemiology , Risk Factors
4.
Front Endocrinol (Lausanne) ; 15: 1369582, 2024.
Article in English | MEDLINE | ID: mdl-38745957

ABSTRACT

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.


Subject(s)
Hydrocortisone , Hyperaldosteronism , Humans , Hyperaldosteronism/surgery , Hyperaldosteronism/metabolism , Hyperaldosteronism/blood , Male , Female , Middle Aged , Hydrocortisone/blood , Retrospective Studies , Adult , Aldosterone/blood , Adrenalectomy , China/epidemiology , Treatment Outcome , Adrenocorticotropic Hormone/blood , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism , Follow-Up Studies , Prognosis
5.
J Assoc Physicians India ; 72(1): 11-12, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38736067

ABSTRACT

Primary aldosteronism (PA), characterized by autonomous renin-independent aldosterone production, is the most common endocrine cause of hypertension.1 PA was initially considered a rare cause of secondary hypertension, as experts described 0.451% prevalence in mild to moderate hypertension when hypokalemia was an essential reason for screening.1 However, recent data suggests that PA may be present even in patients with normokalemia, and 515% of patients in the hypertensive cohort have underlying overt PA.2.


Subject(s)
Hyperaldosteronism , Hypertension , Hyperaldosteronism/diagnosis , Hyperaldosteronism/complications , Humans , Hypertension/etiology , Hypertension/diagnosis , Mass Screening/methods , Hypokalemia/etiology , Hypokalemia/diagnosis , Aldosterone/blood
6.
J Mol Histol ; 55(3): 265-278, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583123

ABSTRACT

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis.


Subject(s)
Aldosterone , Corticosterone , Rats, Wistar , Stress, Psychological , Animals , Male , Aldosterone/blood , Corticosterone/blood , Rats , Stress, Psychological/blood , Stress, Psychological/complications , Fatty Liver/blood , Fatty Liver/etiology , Fatty Liver/pathology , Eplerenone/pharmacology , Kidney/pathology , Kidney/metabolism , Liver/pathology , Liver/metabolism , Fibrosis , Spironolactone/analogs & derivatives , Spironolactone/pharmacology
7.
J Clin Hypertens (Greenwich) ; 26(5): 584-587, 2024 May.
Article in English | MEDLINE | ID: mdl-38605571

ABSTRACT

In patients with primary hyperaldosteronism (PA), adrenal vein sampling (AVS) can identify patients suitable for unilateral adrenalectomy. However, in AVS with an indeterminate aldosterone-to-cortisol lateralization (ACL) ratio of 3.0-4.0, clinical guidance is unclear. The authors screened all patients undergoing AVS at the Cleveland Clinic from October 2010 to January 2021 and identified 18 patients with indeterminate ACL results. Ten underwent adrenalectomy and eight continued medical management. The surgical group was younger (58.5 vs. 68 years, p = .17), and more likely to have a unilateral imaging adrenal abnormality (90% vs. 38%, p = .043) and a lower contralateral suppression index (0.63 vs. 1.1, p = .14). Post-treatment, the surgical group had a significant reduction in diastolic blood pressure (-5.5 mmHg, p = .043) and aldosterone (4.40 vs. 35.80 ng/mL, p = .035) and required fewer anti-hypertensive medications (2 vs. 3, p = .015). These findings may support the benefit of adrenalectomy in a select group of patients with indeterminate ACL.


Subject(s)
Adrenal Glands , Adrenalectomy , Aldosterone , Hydrocortisone , Hyperaldosteronism , Humans , Hyperaldosteronism/surgery , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Middle Aged , Female , Adrenalectomy/methods , Male , Adrenal Glands/blood supply , Adrenal Glands/surgery , Aldosterone/blood , Aged , Hydrocortisone/blood , Antihypertensive Agents/therapeutic use , Retrospective Studies , Veins/surgery , Blood Pressure/physiology , Hypertension/diagnosis , Hypertension/surgery , Ohio/epidemiology , Treatment Outcome
8.
Radiographics ; 44(5): e230115, 2024 May.
Article in English | MEDLINE | ID: mdl-38662586

ABSTRACT

Adrenal vein sampling (AVS) is the standard method for distinguishing unilateral from bilateral sources of autonomous aldosterone production in patients with primary aldosteronism. This procedure has been performed at limited specialized centers due to its technical complexity. With recent advances in imaging technology and knowledge of adrenal vein anatomy in parallel with the development of adjunctive techniques, AVS has become easier to perform, even at nonspecialized centers. Although rare, anatomic variants of the adrenal veins can cause sampling failure or misinterpretation of the sampling results. The inferior accessory hepatic vein and the inferior emissary vein are useful anatomic landmarks for right adrenal vein cannulation, which is the most difficult and crucial step in AVS. Meticulous assessment of adrenal vein anatomy on multidetector CT images and the use of a catheter suitable for the anatomy are crucial for adrenal vein cannulation. Adjunctive techniques such as intraprocedural cortisol assay, cone-beam CT, and coaxial guidewire-catheter techniques are useful tools to confirm right adrenal vein cannulation or to troubleshoot difficult blood sampling. Interventional radiologists should be involved in interpreting the sampling results because technical factors may affect the results. In rare instances, bilateral adrenal suppression, in which aldosterone-to-cortisol ratios of both adrenal glands are lower than that of the inferior vena cava, can be encountered. Repeat sampling may be necessary in this situation. Collaboration with endocrinology and laboratory medicine services is of great importance to optimize the quality of the samples and for smooth and successful operation. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.


Subject(s)
Adrenal Glands , Hyperaldosteronism , Humans , Adrenal Glands/blood supply , Adrenal Glands/diagnostic imaging , Aldosterone/blood , Anatomic Landmarks , Hepatic Veins/diagnostic imaging , Hyperaldosteronism/diagnostic imaging , Multidetector Computed Tomography/methods , Radiography, Interventional/methods , Veins/diagnostic imaging
9.
High Blood Press Cardiovasc Prev ; 31(2): 157-166, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38530572

ABSTRACT

INTRODUCTION: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear. METHODS: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist. Aldosterone-renin-ratio (ARR) was measured on actual medication. RESULTS: Women had a higher prevalence of LV hypertrophy (46% vs. 33%) and LA enlargement (79% vs 65%, both p < 0.05) than men, while drug nonadherence (8% vs. 9%, p > 0.514) did not differ. Women were older and had lower serum renin concentration and higher ARR than men, while 24-h systolic BP (141 ± 9 mmHg vs. 142 ± 9 mmHg), and the prevalences of obesity (43% vs. 50%) did not differ (all p > 0.10). In multivariable analyses, female gender was independently associated with a two-fold increased risk of LV hypertrophy (OR 2.01[95% CI 1.30-3.10], p = 0.002) and LA enlargement (OR 1.90 [95% CI 1.17-3.10], p = 0.010), while no association with drug nonadherence was found. Higher ARR was independently associated with LV hypertrophy in men only (OR 2.12 [95% CI 1.12-4.00] p = 0.02). CONCLUSIONS: Among patients with uncontrolled hypertension, the higher prevalence of LV hypertrophy and LA enlargement in women was not explained by differences in drug nonadherence. REGISTRATION: URL:  https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03209154.


Subject(s)
Antihypertensive Agents , Hypertension , Hypertrophy, Left Ventricular , Medication Adherence , Renin , Aged , Female , Humans , Male , Middle Aged , Aldosterone/blood , Antihypertensive Agents/therapeutic use , Arterial Pressure/drug effects , Atrial Function, Left/drug effects , Atrial Remodeling/drug effects , Biomarkers/blood , Cross-Sectional Studies , Health Status Disparities , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/epidemiology , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/diagnostic imaging , Prevalence , Renin/blood , Risk Assessment , Risk Factors , Sex Factors , Treatment Outcome , Ventricular Function, Left/drug effects , Ventricular Remodeling/drug effects
10.
J Hypertens ; 42(6): 1019-1026, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38527056

ABSTRACT

OBJECTIVE: Adrenal venous sampling (AVS) is key for primary aldosteronism subtype identification. However, the value of adrenocorticotropic hormone (ACTH) stimulation in AVS is still controversial. METHODS: In this prospective study, we investigated the role of continuous ACTH infusion on the performance and interpretation of bilateral simultaneous AVS using a standard protocol in 59 primary aldosteronism patients. We analyzed the selectivity index and lateralization index in AVS pre and post-ACTH and estimated the prognosis of patients who underwent adrenalectomy with different cutoff points of lateralization index post-ACTH. RESULTS: The confirmed success rate of bilateral adrenal vein catheterization increased from 84% pre-ACTH to 95% post-ACTH. Fifty percent of the patients had a decline in lateralization index post-ACTH, 30% of patients showed unilateral primary aldosteronism pre-ACTH but bilateral primary aldosteronism post-ACTH according to lateralization index at least 2 pre-ACTH and lateralization index at least 4 post-ACTH. The outcomes of the patients with primary aldosteronism after adrenalectomy indicated that all patients achieved clinical and biochemical success regardless of lateralization index at least 4 or less than 4 post-ACTH. Receiver operating characteristic curves showed that lateralization index cutoff 2.58 post-ACTH stimulation yielded the best threshold in lateralization with a sensitivity of 73.1% and a specificity of 92.9%. CONCLUSION: ACTH stimulation increased the AVS success rates in patients with primary aldosteronism, reduced lateralization index in some cases and decreased the proportion of identified unilateral primary aldosteronism, resulting in some patients losing the opportunity for disease cure. Compared with lateralization index at least 4, a lower cutoff point of lateralization index at least 2.58 after ACTH stimulation has better accuracy of lateralization diagnosis.


Subject(s)
Adrenal Glands , Adrenocorticotropic Hormone , Hyperaldosteronism , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Hyperaldosteronism/surgery , Hyperaldosteronism/classification , Adrenocorticotropic Hormone/blood , Female , Male , Prospective Studies , Middle Aged , Adrenal Glands/blood supply , Adult , Veins , Adrenalectomy , Aldosterone/blood
11.
Biomed Chromatogr ; 38(6): e5855, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38442715

ABSTRACT

Metabolite profiling has the potential to comprehensively bridge phenotypes and complex heterogeneous physiological and pathological states. We performed a metabolomics study using parallel liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis to screen for biomarkers of primary aldosteronism (PA) from a cohort of 111 PA patients and 218 primary hypertension (PH) patients. Hydrophilic interaction chromatography and reversed-phase liquid chromatography separations were employed to obtain a global plasma metabolome of endogenous metabolites. The satisfactory classification between PA and PH patients was obtained using the MVDA model. A total of 35 differential metabolites were screened out and identified. A diagnostic biomarker panel was established using the least absolute shrinkage and selection operator (LASSO) binary logistic regression model and receiver operating characteristic analysis. Joint analysis with clinical indicators, including plasma supine aldosterone level, plasma orthostatic aldosterone level, body mass index, and blood potassium, revealed that the combination of metabolite biomarker panel and plasma supine aldosterone has the best clinical diagnostic efficacy.


Subject(s)
Biomarkers , Hyperaldosteronism , Mass Spectrometry , Metabolomics , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Metabolomics/methods , Biomarkers/blood , Female , Middle Aged , Male , Mass Spectrometry/methods , Chromatography, Liquid/methods , Metabolome/physiology , Adult , Aldosterone/blood , Liquid Chromatography-Mass Spectrometry
12.
Hypertension ; 81(6): 1391-1399, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38525605

ABSTRACT

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.


Subject(s)
Adrenal Glands , Hyperaldosteronism , Mineralocorticoid Receptor Antagonists , Adult , Female , Humans , Male , Middle Aged , Adrenalectomy/methods , Aldosterone/blood , Blood Pressure/physiology , Blood Pressure/drug effects , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/surgery , Mineralocorticoid Receptor Antagonists/therapeutic use , Propensity Score , Renin/blood , Retrospective Studies , Treatment Outcome , Case-Control Studies
13.
J Perinatol ; 44(5): 643-649, 2024 May.
Article in English | MEDLINE | ID: mdl-38443464

ABSTRACT

OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.


Subject(s)
Aldosterone , Birth Weight , Blood Pressure , Gestational Age , Saliva , Humans , Female , Pregnancy , Mexico , Aldosterone/blood , Adult , Saliva/chemistry , Blood Pressure/physiology , Infant, Newborn , Linear Models , Young Adult , Cohort Studies
14.
Endocr J ; 71(5): 489-497, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38479860

ABSTRACT

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.


Subject(s)
Adrenocorticotropic Hormone , Aldosterone , Cardiovascular Diseases , Cerebrovascular Disorders , Hyperaldosteronism , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/complications , Adrenocorticotropic Hormone/blood , Aldosterone/blood , Male , Female , Middle Aged , Cross-Sectional Studies , Retrospective Studies , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/blood , Aged , Adult , Japan/epidemiology
15.
Hypertens Res ; 47(5): 1362-1371, 2024 May.
Article in English | MEDLINE | ID: mdl-38454147

ABSTRACT

The measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into "negative" based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.


Subject(s)
Aldosterone , Captopril , Hyperaldosteronism , Luminescent Measurements , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Male , Female , Middle Aged , Aldosterone/blood , Retrospective Studies , Adult , Aged , Luminescent Measurements/methods , Immunoenzyme Techniques/methods , Hypertension/blood , Hypertension/diagnosis , Renin/blood , Cohort Studies , Radioimmunoassay
16.
Biomed Chromatogr ; 38(5): e5841, 2024 May.
Article in English | MEDLINE | ID: mdl-38324999

ABSTRACT

Super-selective adrenal venous sampling (ssAVS) can collect the adrenal tributary venous blood in the aldosterone (ALD)-hypersecreting segments in primary aldosteronism. The concentrations of the C18-oxygenated steroids, especially 18-oxocortisol (18-oxoF), in the lesion segments might be more useful indices than those in the peripheral or adrenal central veins (current candidate indexes) for the differential diagnosis of unilateral ALD-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). To verify this hypothesis, we developed a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method for simultaneously quantifying ALD, 18-oxoF and 18-hydroxycortisol in the adrenal tributary venous serum sample collected by ssAVS (ssAVS serum) and compared their concentrations between APA and BAH patients. Only deproteinization was required for a 10 µl sample prior to the LC/ESI-MS/MS analysis. Endogenous corticoids did not interfere with the quantifications, and the intra-assay and interassay precisions (≤ 8.3%) and accuracies (94.2-102.7%) were acceptable. The clinical study revealed that the 18-oxoF concentration was significantly higher in the ALD-producing tumor tissues (from APA patients) than in the hyperplastic tissues (from BAH patients). However, in conclusion, the 18-oxoF concentration in the ssAVS serum sample can be a rough indication but cannot be decisive for the differential diagnosis between APA and BAH owing to the significant individual difference.


Subject(s)
Adrenal Glands , Hydrocortisone/analogs & derivatives , Hyperaldosteronism , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Hyperaldosteronism/blood , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, Liquid/methods , Adrenal Glands/blood supply , Adrenal Glands/chemistry , Adrenal Glands/metabolism , Reproducibility of Results , Male , Middle Aged , Female , Aldosterone/blood , Hydrocortisone/blood , Linear Models , Adult , Aged , Limit of Detection
17.
Am J Hypertens ; 37(6): 415-420, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38374690

ABSTRACT

BACKGROUND: The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS: A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t = 0) after 2 hours (t = 120 min) and after 4 hours (t = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t = 120 to confirm primary aldosteronism. RESULTS: The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t = 240. Mean systolic blood pressure increased from 140.1 ±â€…21.3 mm Hg at t = 0 to 147.6 ±â€…14.5 mm Hg at t = 240 (P = 0.011). CONCLUSIONS: A PAC of 397 pmol/L (14 ng/dL) at t = 120 has high sensitivity and specificity for primary aldosteronism confirmation.


Subject(s)
Aldosterone , Hyperaldosteronism , Renin , Saline Solution , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Pilot Projects , Middle Aged , Male , Female , Aldosterone/blood , Cross-Sectional Studies , Saline Solution/administration & dosage , Renin/blood , Adult , Infusions, Intravenous , Predictive Value of Tests , Biomarkers/blood , Time Factors , Aged , Blood Pressure , Reproducibility of Results
18.
Endocr J ; 71(5): 461-469, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38417879

ABSTRACT

Plasma aldosterone concentration (PAC) was routinely measured using radioimmunoassay (RIA); however, the RIA kit was discontinued in March 2021 in Japan. This study examined PAC conversion in adrenal venous sampling (AVS) and AVS criteria when measured using chemiluminescent enzyme immunoassay (CLEIA). PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) of 63 patients with primary aldosteronism was measured using RIA (Spac-S aldosterone kit; Fujirebio Inc.) and CLEIA (Lumipulse Presto Aldosterone; Fujirebio Inc.). PAC of 70 AVS samples was also measured using liquid chromatography-mass spectrometry (LC-MS/MS, ASKA Pharma Medical Co., Ltd.). PAC conversion formulas were determined for each AVS sample assay. PAC measured using CLEIA was significantly correlated with that measured using RIA (correlation coefficient = 0.971). The PAC conversion formula was PAC (CLEIA) = PAC (RIA) × 0.772 - 1,199 pg/mL. The PAC of 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. PAC measured using CLEIA was also correlated with that measured using LC-MS/MS, and the PAC conversion formula was PAC (CLEIA, pg/mL) = 0.97 × PAC (LC-MS/MS, pg/mL) + 211. The inter-assay coefficient of variability (CV) was 1.1-1.3% and intra-assay CV was 1.0-1.7%, measured using CLEIA. The PAC conversion formula for AVS samples was obtained using CLEIA and RIA, and the conversion formula was different from that for peripheral blood. PAC values measured by CLEIA showed preferable accuracy and high concordance with those measured by LC-MS/MS, even in AVS samples. The study outcomes are useful for interpreting AVS results using non-RIA measurement methods.


Subject(s)
Aldosterone , Hyperaldosteronism , Immunoenzyme Techniques , Radioimmunoassay , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Radioimmunoassay/methods , Radioimmunoassay/standards , Female , Aldosterone/blood , Male , Middle Aged , Immunoenzyme Techniques/methods , Adrenal Glands/blood supply , Adult , Luminescent Measurements/methods , Aged , Tandem Mass Spectrometry/methods , Chromatography, Liquid/methods , Blood Specimen Collection/methods , Japan
19.
J Surg Oncol ; 129(6): 1073-1081, 2024 May.
Article in English | MEDLINE | ID: mdl-38321865

ABSTRACT

OBJECTIVE: To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. METHODS: We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. RESULTS: Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. CONCLUSION: Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.


Subject(s)
Adrenal Gland Neoplasms , Adrenalectomy , Blood Pressure , Hypertension , Humans , Male , Female , Middle Aged , Retrospective Studies , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/metabolism , Adenoma/surgery , Adenoma/metabolism , Adenoma/complications , Adenoma/pathology , Prognosis , Adult , Follow-Up Studies , Aldosterone/blood , Adrenocortical Adenoma/surgery , Adrenocortical Adenoma/complications , Adrenocortical Adenoma/metabolism , Aged
20.
J Clin Endocrinol Metab ; 109(6): e1472-e1475, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38288523

ABSTRACT

Cryoactivation is known to occur in whole blood and plasma samples when kept between +4 and -5 °C, leading to falsely high renin concentrations. In 2022 it has been clearly shown that cryoactivation can also occur in samples stored at -20 °C. Based on these new findings, here we discuss how this can influence the clinical diagnosis of patients. First, we show that storage of renin plasma samples can affect the renin measurements and thereby the aldosterone to renin ratio (ARR) calculation, which might explain the high intraindividual variability in ARR also recently demonstrated. Second, we discuss the existing studies on the establishment of renin reference intervals and note the lack of attention given to this recently revealed preanalytical condition. Our literature review of the reference intervals for renin suggest that cryoactivation might have influenced the published data.


Subject(s)
Aldosterone , Renin , Female , Humans , Aldosterone/blood , Blood Specimen Collection/methods , Blood Specimen Collection/standards , Cryopreservation , Reference Values , Renin/blood , Specimen Handling/standards , Specimen Handling/methods
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