Aldosterone Concentration Research Articles

Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) accurately measures plasma aldosterone concentration (PAC), but its correlation with radioimmunoassay (RIA), equivalent RIA levels, and optimal cutoff for PAC and aldosterone-to-renin ratio (ARR) in primary aldosteronism (PA) screening have not been determined in a Korean population. Our study of 127 patients who underwent diagnostic testing for PA showed that the LC-MS/MS and RIA methods have good correlation, with a mean bias of 29.3% for PAC. An LC-MS/MS PAC level of 11.7 ng/dL was equivalent to an RIA PAC level of 15 ng/dL. Receiver operating characteristic curve analysis showed that an LC-MS/MS PAC level of 10.3 ng/dL and LC-MS/MS ARR level of 20.0 provided sensitivity of 73.1% with a specificity of 57.3% and sensitivity of 92.3% with a specificity of 14.7%, respectively. When the LC-MS/MS method is used for PA screening, an adjustment of cutoff values is necessary.

Comparative analysis of aldosterone and renin assays for primary aldosteronism screening

The transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for plasma aldosterone concentration (PAC) assays has raised concerns over its impact on primary aldosteronism (PA) diagnosis. This study investigated the correlation between PAC and renin values using RIA, CLEIA, and liquid chromatography/mass spectrometry/mass spectrometry (LC–MS/MS), established cutoff values for PA diagnosis using the aldosterone-to-renin ratio (ARR) with PAC_CLEIA, and assessed the differences in PAC values by measuring weak mineralocorticoids (WMs). This retrospective study evaluated 312 serum PAC samples using RIA, CLEIA, and LC–MS/MS, and analyzed 315 plasma renin samples. Method correlations were assessed through Passing-Bablok regression. Receiver operating characteristic curves determined ARR cutoffs for PA diagnosis. WMs were quantified to evaluate their impact on ΔPAC (RIA-LC–MS/MS) through multiple regression analysis. PAC_CLEIA and PAC_LC-MS/MS values were highly correlated. ARRs derived from PAC_RIAs demonstrated more false positives and lower specificity than ARRs using PAC_CLEIA or PAC_LC-MS/MS. WMs significantly influenced ΔPAC in both the PA and non-PA groups. ARRs using PAC_CLEIA are valuable for determining PA cutoffs in clinical practice. The transition to PAC using CLEIA may enhance PA detection rates. WMs were found to interfere with PAC measurements in the RIA method, affecting outcomes.

Relationship between renin, aldosterone, aldosterone-to-renin ratio and left ventricular mass index in young adults

Abstract Background Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, especially in middle-aged and elderly populations. It is unclear if early changes in PA biomarkers can affect left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases. Aim To evaluate the relationship between PA biomarkers, namely renin concentration, aldosterone concentration and aldosterone-to-renin ratio (ARR), and LVMI in young adults. Methods The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27. Participants with PA biomarkers and LVMI measured by cardiac magnetic resonance imaging were included. Females who were on oral contraception were excluded due to its confounding effect on the ARR. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results Of 758 participants, 252 (33.2%) were females and the mean (SD) age was 26.7 (0.4) years. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m²; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusion An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function. One may speculate that an intervention trial in young adults with subclinical PA is warranted to determine the role of aldosterone blockade in preventing future cardiovascular diseases.

Development of a multivariate model predictive of post-adrenalectomy renal function decline in patients with primary aldosteronism: a large-cohort single-center study.

To develop a multivariate liniear model for predicting long-term (> 3 months) post-adrenalectomy renal function decline in patients with primary aldosteronism (PA). The model aims to help identify patients who may experience a significant decline in renal function after surgery. We retrospectively analyzed the clinical data of 357 patients who were diagnosed with PA and underwent adrenalectomy between September 2012 and February 2023. LASSO and multivariate linear regression analyses were used to identify significant risk factors for model construction. The models were further internally validated using bootstrap method. Age (P < 0.001), plasma aldosterone concentration (PAC) measured in the upright-position (PACU, P = 0.066), PAC measured after saline infusion (PACafterNS, P = 0.010), preoperative blood adrenocorticotropic-hormone level (ACTH, P = 0.048), preoperative estimated glomerular filtration rate (eGFR, P < 0.001) and immediate postoperative eGFR (P < 0.001) were finally included in a multivariate model predictive of post-adrenalectomy renal function decline and the coefficients were adjusted by internal validation. The final model is: predicted postoperative long-term (> 3 months) eGFR decline =-70.010 + 0.416*age + 6.343*lg PACU+4.802*lg ACTH + 7.424*lg PACafterNS+0.637*preoperative eGFR-0.438*immediate postoperative eGFR. The predicted values are highly related to the observed values (adjusted R = 0.63). The linear model incorporating perioperative clinical variables can accurately predict long-term (> 3 months) post-adrenalectomy renal function decline.

Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma.

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.

High chloride induces aldosterone resistance in the distal nephron.

Increasing the dietary intake of K+ in the setting of a high salt intake promotes renal Na+ excretion even though K+ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na+ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na+ reabsorption after high K+ intake. Mice were fed diets containing varying amounts of Na+ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl-]. The response to aldosterone was analyzed by high-resolution imaging and by biochemical approaches. The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na+ channel ENaC was repressed in Na+-replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na+-replete mice when the extracellular [Cl-] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl-] was sufficient to disrupt the aldosterone-induced MR translocation. These findings indicate a pivotal role for extracellular [Cl-] in modulating renal aldosterone signaling to adapt MR activation by a high K+ intake to the NaCl balance. An impairment of [Cl-]-mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects.

Rising Prevalence of Obesity and Primary Hyperaldosteronism: Co-incidence or Connected Circumstances Leading to Hypertension? A Narrative Review.

While obesity and its associated complications, mainly diabetes and hypertension, have been the largest public health problems of modern world, the emerging data suggests an increasing prevalence of primary hyperaldosteronism (PA) as one of the most common undiagnosed causes of hypertension. We believe that rising prevalence of PA in the era of high rates of obesity is likely not a chance finding but is deeply intersected with the rising rates of obesity. Higher serum aldosterone concentrations and urinary aldosterone excretion have been observed in patients with increased body mass index or larger waist circumference. The in vitro and pre-clinical studies suggest that adipocytes not only synthesize and secrete aldosterone but also release factors which stimulate production of aldosterone from adrenal glands. Aldosterone excess causing ligand-dependent activation of the mineralocorticoid receptor (MR) has increasingly been recognized as one of the important mechanisms of obesity-related hypertension. The aldosterone excess in these cases can be labelled as acquired hyperaldosteronism to differentiate it from the non-obesity related classical cases of PA. Because of serious consequences, recognizing aldosterone excess in obesity is important, as it gives a more compelling reason for weight loss and guidance to choosing pharmacotherapy wisely. Dietary sodium restriction and mineralocorticoid receptor antagonists play important roles in the management of PA associated with obesity.

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.

Manganese nanoparticles catalyzed the formation of mesoporous helical nitrogen-doped carbon nanotubes enabled aldosterone biosensing

Primary aldosteronism (PA) is the foremost form of secondary hypertension that affects 5–20 % of healthy humans via the excessive secretion of aldosterone (ALD), which increases the level of potassium excretion and thus produces various critical combined diseases. Thus, determining trace-level ALD content in human blood or urine samples is a crucial factor in diagnosing a life-threatening disease called PA. Herein, nanosized manganese particles encapsulated within the tunable helical-shaped N-doped mesoporous carbon nanotubes (Mnx@H-NCNTs) are synthesized by a simple and facile ball-milling method at different reaction times (1, 6, 12, and 18 h). The influence of ball-milling process time on the final morphology of the as-synthesized Mnx@H-NCNTs nanostructures is systematically investigated. In order to fabricate an ALD biosensor electrode, the immobilization of Anti-ALD antibodies (Anti-ALD) on the surface of the Mn@H-NCNTs-12H electrode (Anti-ALD/Mn@H-NCNTs-12H) is achieved via the interactions of combined interactions of hydrogen bonds, Van der Waals’ force, negatively charged carboxylic acid functionalities of antibodies and positively charged metal centers, and π-π stacking interaction between nucleosides of Anti-ALD and mesoporous H-NCNTs. In addition, BSA was used as a blocking additive for covering non-specific adsorption sites of Anti-ALD/Mnx@H-NCNTs (BSA/Anti-ALD/Mn@H-NCNTs-12H) nanostructured electrodes. The BSA/Anti-ALD/Mn@H-NCNTs-12H can be used as an effective signal amplifying probe for ALD detection through a noticeable reduction in the amperometric i-t current response over a linear range from 1 to 2500 pM, with a LOD of 0.72 pM (S/N = 3). The practical applicability of BSA/Anti-ALD/Mn@H-NCNTs-12H is further demonstrated by the detection of ALD from 1 to 20 nM in human blood or urine samples with a recovery ranging from 90.5 to 97.0 %, indicating its potential use in clinical analysis.

Role of aldosterone in various target organ damage in patients with hypertensive emergency: a cross-sectional study

BackgroundHypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies.MethodsWe enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed.ResultsAmong 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]).ConclusionIn patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

ACTH stimulation and oral salt loading tests detect biochemical outcome early after primary aldosteronism surgery.

In primary aldosteronism (PA), the biochemical outcomes of the Primary Aldosteronism Surgical Outcome study are used to assess aldosterone hypersecretion 6-12 months after surgery. However, few studies have investigated whether the outcomes can be predicted in the early postoperative period. In this retrospective study, we evaluated whether the adrenocorticotropin stimulation test (AST) and oral salt loading test (OST) performed immediately after surgery could predict biochemical outcomes 1 year after surgery. We assessed 268 patients with PA who underwent adrenalectomy at our hospital between 2008 and 2020, underwent AST and OST within 15 days of surgery, and were assessed for biochemical outcomes 1 year after surgery. Patients were divided into two groups: biochemical complete success (B-com; n = 219) and incomplete success (B-inc; n = 49). Patients were divided into clinical complete and partial success and absent success groups. The relationships between various AST and OST values and outcomes were analyzed. The B-inc group had significantly higher plasma aldosterone concentration (PAC) and PAC/serum cortisol ratio (PAC/Cort) at baseline and after ACTH loading in AST and 24-hour urine aldosterone in OST than the B-com group. PAC/Cort at 30 min after ACTH loading (area under the curve (AUC) = 0.76) and 24-hour urine aldosterone (AUC = 0.77) were relatively superior predictors of the outcome. Parameters after ACTH loading were better predictors of biochemical and clinical outcomes than baseline. AST and OST immediately after surgery can predict biochemical and clinical outcomes 1 year after surgery in patients with PA.

5165 Cushing’s Disease And Primary Aldosteronism Confounded By A Non-functioning Solitary Adrenal Incidentaloma

Abstract Disclosure: J.G. Friedman: None. W. Huang: None. Background: Adrenal incidentalomas are common, affecting ∼2% of the general population. The presence of adrenal incidentaloma necessitates biochemical testing for hypersecretion, however hypercortisolism and/or hyperaldosteronism may not necessarily originate from the nodule that prompted the initial workup. Clinical Case: A 53-year-old man with a history of obesity and hypertension was referred for workup of a 2.4 x 1.4 cm R adrenal nodule that was incidentally discovered on an abdominal CT to rule out pancreatitis. He was noted on examination to have some Cushingoid features. He was on three antihypertensives (amlodipine 10 mg, carvedilol 50 mg, and spironolactone 50 mg) with adequate blood pressure control and no hypokalemia. He denied spells nor exogenous steroid exposure. Initial testing for hypersecretion showed an elevated cortisol 8.7 ug/dL (&amp;lt;1.8) after 1 mg dexamethasone with adequate dexamethasone level, aldosterone concentration (PAC) 9 ng/dL (3-16), plasma renin activity (PRA) 0.7 ng/mL/h (0.25-5.82), potassium of 3.8 mmol/L (3.5-5.1), and normal plasma metanephrines. Further testing revealed elevated 24-hour urinary free cortisol 81.3 mcg/24h (4-50) and elevated late night salivary cortisol 0.10 and 0.13 mg/dL (&amp;lt;0.09). Baseline 8 AM ACTH was not suppressed 16.3 pg/mL (7.2-63.6). DDAVP stimulation resulted in an increase in cortisol and ACTH suggestive of Cushing’s disease, which was confirmed by inferior petrosal sinus sampling (IPSS). Pituitary MRI showed a 3.6 mm L-sided microadenoma. He underwent transsphenoidal resection with pathology consistent with an ACTH-staining pituitary adenoma. Immediate post-op cortisol nadir was 4.9 ug/dL. A few weeks after surgery, he underwent retesting for primary aldosteronism notable for PAC 14 ng/dL, PRA 0.58 ng/mL/h, and K 4.0 mmol/L. After oral salt loading, 24-hour urine aldosterone was 14.4 mcg/24h (&amp;lt;12) with urine sodium 247 mmol/L/24h (&amp;gt;200). He completed AVS which lateralized to the L adrenal gland despite a R adrenal nodule. He underwent L adrenalectomy with significant improvement in blood pressure which is now well-controlled on carvedilol monotherapy with normalization of PRA to 1.94 ng/ml/h. The R adrenal nodule remains stable in size and appearance on follow up imaging. Conclusion: The presence of an adrenal adenoma with concomitant biochemical evidence of hormonal excess cannot inherently be attributed to nodular autonomous function without further workup. Other hormonal assessment including ACTH level and localization studies are necessary prior to any surgical procedure to avoid missed diagnoses of Cushing’s disease and contralateral primary aldosteronism in the presence of a non-functioning adrenal nodule. Presentation: 6/1/2024

6966 A Rhythmic Life-Threatening Enigma Unveiled: KCNH2 Mutation-Associated Torsades de Points Unmasking Primary Hyperaldosteronism in Cardiological Realm

Abstract Disclosure: S. Dejprapasorn: None. N. Nopparatana: None. S. Soonthornpun: None. R. Leelawattana: None. N. Kietsiriroje: None. S. Limumpornpetch: None. T. Nilmoje: None. W. Lohawijarn: None. T. Wongsuttipakorn: None. P. Choochuen: None. P. Limumpornpetch: None. Introduction: Primary hyperaldosteronism (PA) is characterized by hypertension and hypokalemia. However, its ability to masquerade life-threatening Torsades de Pointes makes it an unusual and dismissed diagnosis, revealing the link between PA and serious arrythmia. Clinical Case A 30-year-old female experienced three episodes of palpitations, followed by syncope. Upon admission, her blood pressure was 147/87 mmHg. ECG showed prolonged QT intervals with potassium level was 2.6 mmol/L (3.5-5.0 mmol/L). Continuous cardiac monitoring captured Torsades de Pointes. Despite potassium replacement, long QT still persisted. Pathogenic variant, c.2592+1G&amp;gt;A, within KCNH2 was discovered. Aldosterone concentration showed 69.65 ng/dL (9.70-62.60 ng/dL) and plasma renin activity was 0.12 ng/mL/h (1.50-5.70 ng/mL/h). Aldosterone-to-renin ratio was 580. Aldosterone post 4-h saline infusion test was 31.71 ng/dL which were consistent with PA. Adrenal unenhanced CT scan identified bilateral adrenal nodules (right 1.3 cm, left 1.1 cm). After receiving a cardioverter-defibrillator and spironolactone, the patient has had no palpitations, and their potassium level has remained normal. Clinical lessons: PA rarely presents ventricular arrhythmia. KCNH2 mutation may link between long QT syndrome (LQTS) and PA arises. LQTS type 2 is attributable to KCNH2 mutations, impacting potassium channel subunits crucial for adjusting currents during sympathetic activation. This is essential for shortening the QT interval with increasing heart rate. KCNH2 mutations disrupt this process, prolonging the QT interval and heightening the risk of arrhythmias. Aldosterone synthesis relies on calcium signaling triggered by potassium currents. Adrenal cortex hosts approximately 90 potassium channels genes, including KCNJ5 and KCNH2. Mutations in gene can disrupt the calcium signaling cascade, leading to excessive aldosterone production. While KCNJ5 mutation is well-documented in PA, the potential correlation between KCNH2 mutations and a similar mechanism remains unexplored in clinical reports to date. This case highlights the importance of a thorough comprehension of genetic cause contributing to pathogenesis of PA with complex clinical presentations. Presentation: 6/1/2024

7211 Clinical and Molecular Characterization Of An Aldosterone-Producing Adenoma Harboring Double Somatic Mutations In CTNNB1 and GNA11

Abstract Disclosure: A. Blinder: None. K. Nanba: Grant Recipient; Self; AstraZeneca. A. Udager: None. Y. Hirokawa: None. T. Miura: None. H. Okuno: None. K. Moriyoshi: None. Y. Yamazaki: None. H. Sasano: None. A. Yasoda: None. N. Satoh-Asahara: None. W.E. Rainey: None. T. Tagami: None. Background: Somatic activating mutations in CTNNB1, encoding β-catenin, have been detected in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q, encoding guanine nucleotide-binding protein subunits alpha-11 and alpha-Q, in APA. However, due to its rare incidence, clinical and molecular features of APA associated with these mutations have not been well characterized. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Clinical Case: A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycles at presentation. Laboratory testing showed elevated plasma aldosterone concentration with suppressed plasma renin activity. She was diagnosed as having primary aldosteronism based on the results of a captopril challenge test. Adrenal computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the criteria of Weiss. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. According to the primary aldosteronism surgical outcome (PASO) study criteria, PA remained clinically and biochemically cured at follow-up 2.5 years after surgery. Results: Immunohistochemistry (IHC) showed high and diffuse expression of aldosterone synthase (CYP11B2) within the tumor, whereas immunoreactivity of 17α-hydroxylase (CYP17A1) and 11β-hydroxylase (CYP11B1), both required for cortisol biosynthesis, was markedly low. VSNL1, a marker for the zona glomerulosa (ZG) where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided tumor capture followed by targeted next-generation sequencing identified double somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Quantitative real-time RT-PCR revealed high tumor expression of LHCGR (LH receptor) and GNRHR (GNRH receptor) mRNA levels compared with those in adjacent normal adrenal (148-fold and 56-fold, respectively). Immunofluorescence staining of the tumor revealed the presence of activated β-catenin, consistent with features of the normal ZG. Conclusions: Our study indicates that an APA with double somatic mutations in CTNNB1 and GNA11 has characteristics of the ZG and could occur in adults with no clear association with pregnancy or menopause. Presentation: 6/3/2024

6744 Clinical Profile And Outcomes Of Medically And Surgically Managed Patient With Primary Hyperaldosteronism In A Third-World World Setting

Abstract Disclosure: A.A. Apa-ap: None. E.P. Pacheco: None. Background: Assessing therapeutic response in Primary hyperaldosteronism (PA) has previously been significantly hampered by a lack of standardized outcome markers. Although most participants in observational studies benefit from both medical and surgical therapy, comparative analyses have been limited. To date, no available Filipino data comparing therapeutic responses have been published. This paper aims to answer the clinical profile and outcomes of patients with PA in a third-world setting. Method: This is a retrospective cohort study that includes adult patients diagnosed with PA in the Philippine General Hospital seen at the outpatient department and admitted from January 1, 2013, until December 31, 2022. Result: 57 patients with PA were identified on chart review. A total of 40 (70%) patients were included in the study. 17 patients were excluded due to missing data. All patients had a unilateral adrenal mass. 23 patients underwent adrenalectomy and grouped under surgical management. 17 patients were treated with antihypertensive including MRA and grouped under medical management. Out of the 40 patients included: 83% were women, mean age was 40, hypertension averaged 6 years and 92.5% had hypokalemia. Radiologic profile showed mean tumor size 1.7cm and and mean tumor density 11.7 HU, mean absolute washout of 68.8 HU, and mean relative washout 54.8 HU. Comparing the post-treatment clinical outcome between surgical and medical management showed that patients who underwent surgical treatment had significantly lower systolic (difference=-11.12, p=0.0012) and diastolic blood pressure (difference= -6.03, p=0.0264), mean number of antihypertensive medication (difference= -2.30, p&amp;lt;0.001), mean daily dose of antihypertensive(difference= -3.43, p&amp;lt;0.001). Both groups had normal serum K post-treatment, but patients who underwent surgical treatment had significantly higher mean serum K (difference= 0.41, p=0.0025) and none had required MRA post-op. There was a lower number of patients with left ventricular hypertrophy and a significantly higher ejection fraction (difference= 5.81, p=0.0038) post-op compared to patients who underwent medical management. In terms of biochemical profile, there was a significantly lower mean plasma aldosterone concentration (difference= -31.95, p&amp;lt;0.001), and mean aldosterone/renin activity (difference= -211.51, p=0.0013) and significantly higher mean plasma renin activity (difference= 0.43, p&amp;lt;0.001) after surgery compared to those who underwent medical management. All surgical patients had a histopathologic diagnosis of adrenocortical adenoma. 9 patients complete clinical success and 14 had partial clinical success post-op; 22 had complete biochemical success and 1 had partial biochemical success based on PASO consensus. Conclusion: This study showed better clinical outcomes in patients with PA who underwent surgical management. Presentation: 6/1/2024

Potential impact of severe hydronephrosis secondary to ureteropelvic junction obstruction on pediatric blood pressure

Hydronephrosis could affect blood pressure (BP) according to published case reports and animal experiments. The impact on pediatric BP is often overlooked due to children's inherently lower BP, superior vascular elasticity and greater resistance to hypertension than adults. This study aimed to prospectively observe the effects of hydronephrosis, secondary to ureteropelvic junction obstruction (UPJO), on pediatric BP. Children with hydronephrosis secondary to UPJO who required pyeloplasty were categorized into five age groups: neonates, infants, toddlers, preschoolers, and school-aged children. Preoperative and postoperative systolic blood pressure (SBP), diastolic blood pressure (DBP), active renin concentration (ARC), and aldosterone concentration (AC) were compared among these age groups, followed by comparison with a control group of children without nephritis or cardiovascular conditions. The impact of severe hydronephrosis secondary to UPJO on pediatric BP and its association with the renin-angiotensin-aldosterone system (RAAS) were examined. This study enrolled 114 children with severe hydronephrosis secondary to UPJO and 153 without nephritic or cardiovascular conditions between September 2021 and June 2023. As the control group aged, SBP and DBP increased, whereas ARC and AC decreased. Overall, hydronephrosis group had higher SBP, DBP, ARC, and AC than the controls group. These differences differed between the age groups. After pyeloplasty, the postoperative BP of hydronephrosis group approximated that of the control group. Postoperative ARC levels were higher than those in the control group but were much lower than the preoperative levels. AC did not decrease significantly after surgery. The change in DBP in children with hydronephrosis before and after pyeloplasty showed a positive correlation with the change in AC. Pediatric patients with severe hydronephrosis, a condition secondary to UPJO, displayed elevated BP, ARC, and AC. Following pyeloplasty, these patients noted a reduction in BP. The correlation between elevated blood pressure and the RAAS necessitates further comprehensive investigation.

Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults.

Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006-2009) and 27 (2016-2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P<0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P<0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P<0.001) and 27 (21.0 versus 15.6; P<0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 [95% CI, 0.001-0.017]; P=0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 [95% CI, 0.001-0.196]; P=0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.

Placenta may exert fetal protection against maternal high salt diet intake via renin-angiotensin-aldosterone system

ObjectiveThis study investigated the effects of high compared to normal dietary salt intake on fetoplacental vascular function, activity of renin-angiotensin-aldosterone system (RAAS), placental pro- and anti-angiogenic factors and biomarkers of placental remodeling and oxidative stress during healthy uncomplicated pregnancy. Materials and MethodsBased on their 24-hour sodium excretion pregnant women (37–40 weeks’ gestation) were categorized into three groups: normal salt (NS, <5.75 g/day, N=12), high salt (HS, 5.75–10.25 g/day, N=36), and very high salt (VHS, >10.25 g/day, N=17). Pulsatility (PI) and resistive index of middle cerebral artery (MCA) and umbilical artery, plasma renin activity (PRA), serum aldosterone, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations, as well as placental vascular endothelial growth factor C (VEGF-C), oxidative/antioxidative stress markers (TBARS/FRAP) and matrix metalloproteinase 9 (MMP-9) concentration were measured. ResultsPI MCA was significantly decreased in HS/VHS groups compared to NS group. HS/VHS intake did not suppress PRA and aldosterone concentration. Serum PlGF concentration was significantly increased while sFlt-1 concentration and sFlt-1/PlGF ratio were significantly decreased in VHS group compared to NS group. MMP-9, VEGF-C concentration, TBARS and FRAP in placental tissue were similar between study groups. ConclusionsHS/VHS diet does not suppress RAAS during pregnancy; however, it is associated with decreased PI MCA, a significantly decreased sFlt-1/PlGF ratio and unchanged biomarkers of placental remodeling or oxidative stress in healthy pregnant women, suggesting the presence of a possible protective or compensatory mechanism aimed at preserving placental function and pregnancy outcome itself in terms of maternal HS intake.

Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism.

In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR. We compared 2 potential screening approaches to identify probable primary aldosteronism (ARR≥30 or ARR≥20 versus PRA suppressed below 1 ng/mL per h) in a cohort of 94 829 paired PRA and PAC samples submitted by clinicians to evaluate the presence of primary aldosteronism. Of 94 829 patients, 20.3% tested positive based on ARR≥20 (95% CI, 20.0%-20.5%), 13.9% based on ARR≥30 (95% CI, 13.6%-14.1%), versus 45.9% based on suppressed PRA (<1 ng/mL per minute [95% CI, 45.5%-46.2%]). In the PRA group, a range of aldosterone levels was observed: 5.5% had PAC >15 ng/dL, 25.2% had PAC 5 to 15 ng/dL, and 15.2% had PAC <5 ng/dL, compared with 6%, 12.7%, and 1.6% in the ARR≥20 group and 4.7%, 8.5%, and 0.7% in the ARR≥30 group. In this cohort of individuals being screened for primary aldosteronism, substantially more individuals were identified using criteria focused on suppression of renin activity compared with using the aldosterone renin ratio as a screening tool.

Comparison between typical primary and eunatraemic, eukalaemic hypoadrenocorticism: 92 cases

BackgroundNaturally occurring hypoadrenocorticism is an uncommon endocrine disorder in dogs but has significant morbidity and mortality. Some dogs present with apparent glucocorticoid deficiency alone as evidenced by eunatraemia and eukalaemia. Few studies have compared dogs with hypoadrenocorticism with or without electrolyte disturbances and there are no large case series of affected dogs from Ireland.MethodsRetrospective observational study.ResultsNinety-two cases diagnosed with hypoadrenocorticism subdivided into those with supportive electrolyte disturbances (Group 1; n = 72) and those without (Group 2; n = 20). Dogs in Group 1 were significantly (p = 0.001) younger (4.0 (3.0–6.0) years) than dogs in Group 2 (6.0 (4.75–8.25) years). Dogs in Group 1 presented significantly more commonly with vomiting (Group 1: 52/71 (73.2%), Group 2: 6/20 (30.0%); p < 0.001), total hyperproteinaemia (Group 1: 21/71 (29.6%), Group 2: 1/20 (5.0%); p = 0.023), increased urea (Group 1: 52/72 (72.2%), Group 2: 5/20 (25.0%); p < 0.001), increased creatinine (Group 1: 31/72 (43.1%), Group 2: 3/20 (15.0%); p = 0.021) and hyperphosphataemia (Group 1: 40/71 (56.3%), Group 2: 2/20 (10.0%); p < 0.001), and significantly less commonly with reticulocytosis (Group 1: 4/38 (10.5%), Group 2: 5/13 (38.5%), p = 0.023). An undetectable basal aldosterone concentration had a positive predictive value of 94.3% for diagnosing undetectable post-ACTH aldosterone concentration. Of the thirteen dogs in Group 2 that had aldosterone concentrations measured and secondary disease excluded, 7 (53.8%) had or subsequently developed evidence of aldosterone deficiency, although not always with electrolyte abnormalities.ConclusionsDogs with hypoadrenocorticism from Ireland are similar to other reported cases. An undetectable basal aldosterone concentration is highly predictive of mineralocorticoid deficiency. Dogs with apparent glucocorticoid deficiency alone can progress to more typical disease and should be monitored appropriately.