The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

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.

Surgical versus medical management of patients with primary hyperaldosteronism and indeterminate adrenal vein sampling: A 10-year experience of the Cleveland Clinic.

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.

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.

Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study.

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.

Untargeted metabolomics reveals potential plasma biomarkers for diagnosis of primary aldosteronism using liquid chromatography-mass spectrometry.

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.

Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling for the subtyping of primary aldosteronism: a prospective study.

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.

A 120-Minute Saline Infusion Test for the Confirmation of Primary Aldosteronism: A Pilot Study.

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.

Determination of three C18-oxygenated steroids in adrenal lesion segments in primary aldosteronism by super-selective adrenal venous sampling and LC/ESI-MS/MS.

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.

Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

Recent Advances in the Clinical Application of Adrenal Vein Sampling.

We reviewed clinical research investigating the applications of adrenal vein sampling (AVS). AVS could be applied not only to primary aldosteronism (PA) but also to other endocrine diseases, such as adrenocorticotropic hormone (ACTH) independent Cushing syndrome (AICS) and hyperandrogenemia (HA). However, the AVS protocol requires improvements to increase its success rate. Using the computed tomography image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing (CCF) technique could improve the success rate of catheterization in AVS for PA. ACTH loading could be considered in medical centers with a low selectivity of AVS for PA but is not essential in those with mature AVS technology. The continuous infusion method should be recommended for ACTH stimulation in AVS for PA to reduce adverse events. AVS has not been routinely recommended before management decisions in AICS, but several studies verified that AVS was useful in finding out the source of excess cortisol, especially for distinguishing unilateral from bilateral disease. However, it is necessary to reassess the results of AVS in AICS with the use of reference hormones to fully normalize cortisol levels. In addition, it is essential to determine the optimal model that combines AVS results and mass size to guide the selection of surgical plans, including identifying the dominant gland and presenting the option of staged adrenalectomy, to minimize the impact of bilateral resection. For HA, AVS combined with ovarian intravenous sampling to locate excess androgens could be considered when imaging results are equivocal.

Screening Rates for Primary Aldosteronism Among Individuals With Hypertension Plus Hypokalemia: A Population-Based Retrospective Cohort Study.

Primary aldosteronism is a common, yet highly underdiagnosed, cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Hypertension plus hypokalemia is a guideline-recommended indication to screen for primary aldosteronism, yet the uptake of this recommendation at the population level remains unknown. We performed a population-based retrospective cohort study of adults ≥18 years old in Ontario, Canada, with hypertension plus hypokalemia (potassium <3.5 mEq/L) from 2009 to 2015 with follow-up through 2017. We measured the proportion of individuals who underwent primary aldosteronism screening via the aldosterone-to-renin ratio based upon hypokalemia frequency and severity along with concurrent antihypertensive medication use. We assessed clinical predictors associated with screening via Cox regression. The cohort included 26 533 adults of which only 422 (1.6%) underwent primary aldosteronism screening. When assessed by number of instances of hypokalemia over a 2-year time window, the proportion of eligible patients who were screened increased only modestly from 1.0% (158/15 983) with one instance to 4.8% (71/1494) with ≥5 instances. Among individuals with severe hypokalemia (potassium <3.0 mEq/L), only 3.9% (58/1422) were screened. Among older adults prescribed ≥4 antihypertensive medications, only 1.0% were screened. Subspecialty care with endocrinology (hazard ratio [HR], 1.52 [95% CI, 1.10-2.09]), nephrology (HR, 1.43 [95% CI, 1.07-1.91]), and cardiology (HR, 1.39 [95% CI, 1.14-1.70]) were associated with an increased likelihood of screening, whereas age (HR, 0.95 [95% CI, 0.94-0.96]) and diabetes (HR, 0.66 [95% CI, 0.50-0.89]) were inversely associated with screening. In conclusion, population-level uptake of guideline recommendations for primary aldosteronism screening is exceedingly low. Increased education and awareness are critical to bridge this gap.

Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.

CONTEXT: Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need. OBJECTIVE: This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma. METHODS: This retrospective cross-sectional study, which took place at 7 European tertiary-care centers, comprised 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma (PHEO), primary aldosteronism (PA), autonomous cortisol secretion (ACS), and nonfunctional adrenal incidentaloma (NFAI). Mesaures of diagnostic performance were assessed (with [95% CIs]) for discriminating different subgroups of patients with adrenal incidentaloma. RESULTS: Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol, and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA, and PHEO at respective sensitivities of 83.3% (66.1%-100%), 90.8% (83.7%-97.8%), and 94.8% (89.8%-99.8%); and specificities of 98.0% (96.9%-99.2%), 92.0% (89.6%-94.3%), and 98.6% (97.6%-99.6%). With the addition of tumor size, discrimination improved further, particularly for ACC (100% [100%-100%] sensitivity, 99.5% [98.9%-100%] specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70%-71% sensitivity, 89%-90% specificity). CONCLUSION: Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate the identification of almost all clinically relevant adrenal tumors.

Reassessment of Postural Stimulation Testing as a Simple Tool to Identify a Subgroup of Patients With Unilateral Primary Aldosteronism.

CONTEXT: Adrenal vein sampling (AVS) represents the current diagnostic gold standard for differentiation between unilateral and bilateral primary aldosteronism (PA). Postural stimulation testing (PST) has been used to provide additional diagnostic information. OBJECTIVE: This work aimed to evaluate the diagnostic utility of PST in the differential diagnosis of PA. METHODS: This cohort study was conducted at a single tertiary reference center. We analyzed 106 PST performed between 2008 and 2020. Diagnosis of PA and cause of PA were determined according to the Endocrine Society Clinical Practice Guideline, taking into account results of saline infusion testing, AVS, preoperative imaging, and outcome after medical or surgical treatment. The suggested cutoffs for the diagnosis of unilateral PA were revisited and optimized for high specificity using receiver operating characteristics (ROC) analysis. RESULTS: A total of 106 patients had confirmed PA (unilateral PA: n = 55, bilateral PA: n = 29, AVS unsuccessful/declined by patients: n = 22). Based on decreased aldosterone plasma concentration of 28% or more after 4 hours in the upright position, the PST showed a sensitivity of 36.4% at a specificity of 100% to identify unilateral disease (area under the curve [AUC] = 0.72; 95% CI, 0.62-0.83; P = .001). In patients with valid testing (drop of cortisol of 10% or more after 4 hours, n = 53) the sensitivity of PST rose to 51.4% at a specificity of 100% (AUC = 0.77; 95% CI, 0.65-0.90; P = .001). CONCLUSION: The high specificity of 100% for the detection of unilateral PA in patients with decreased aldosterone by at least 28% after 4 hours makes PST a simple, noninvasive contribution to subtype differentiation in PA.

Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Comparison of Bolus and Continuous Infusion of Adrenocorticotropic Hormone During Adrenal Vein Sampling.

Background: Adrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs). Methods: Retrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed. Results: The study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group. Conclusions: Due to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.

Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics.

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population. The aim of the current analysis was to describe the baseline characteristics of the first 100 patients eligible for study inclusion. The recruitment of patients with hypokalemia (≤3 mmol/l) is carried out continuously on a referral-basis by the central laboratory of the University Hospital Zurich through an automated suitability testing and data delivery system. The careful evaluation of the first 100 reported patients was based on the available reporting system. Out of 28 140 screened patients, 222 (0.79%) were identified with a serum potassium value of≤3 mmol/l (mean 2.89±0.02 mmol/l). Mean potassium levels were slightly lower in non-hypertensive subjects compared to hypertensive subjects (mean difference 0.07 mmol/l, p=0.033), while no significant difference was found between the sexes and patients with and without the diagnosis of primary aldosteronism, atrial fibrillation, or the use of diuretics. The incidence of PA was 4% in the total population studied and 7.5% in the subgroup of hypertensive patients. In conclusion, the continuous enrollment of patients from the IPHAK+hypokalemia registry into the IPAHK+trial will provide evidence about the actual incidence of primary aldosteronism in a hypokalemic outpatient population.

Positive Association Between Plasma Aldosterone Concentration and White Matter Lesions in Patients With Hypertension.

Background and Objective: White matter lesions (WMLs) are imaging changes in MRI of cerebral small vessel disease associated with vascular risk factors, increasing the risk of dementia, depression, and stroke. Aldosterone (ALD) or activation of mineralocorticoid receptor (MR) causes cerebrovascular injury in a mouse model. We aimed to analyze the relationship between ALD and WMLs in a population with hypertension. Methods: We conducted a retrospective review of all patients screened for causes of secondary hypertension. We enrolled 547 patients with WMLs and matched these to controls without WMLs at a 1:1 ratio. White matter lesion load was assessed by using a modified Scheltens' scale. Results: Among the analytic sample (N = 1,094) with ages ranging from 30 to 64 years, 62.2% were male. We divided plasma ALD concentration (PAC), plasma renin activity (PRA), and ALD-renin ratio (ARR) into the third tertile (Q3), second tertile (Q2), and first tertile (Q1). We also analyzed them simultaneously as continuous variables. Multivariate logistic regression analysis showed that participants in Q3 (>17.26 ng/dl) of PAC (OR 1.59, 95% CI 1.15, 2.19), Q3 (<0.80 ng/dl) of PRA (OR 2.50, 95% CI 1.81, 3.44), and Q3 (>18.59 ng/dl per ng/ml*h) of ARR (OR 2.90, 95% CI 2.10, 4.01) had a significantly higher risk of WMLs than those in Q1 (<12.48) of PAC, Q1 (>2.19) of PRA, and Q1 (<6.96) of ARR. In linear regression analysis, we separately analyzed the correlation between the modified Scheltens' scale score and log(PAC) (ß = 2.36; 95% CI 1.30, 3.41; p < 0.001), log(PRA) (ß = -1.76; 95% CI -2.09, -1.43; p < 0.001), and log(ARR) (ß = 1.86; 95% CI 1.55, 2.17; p < 0.001), which were all significantly correlated with white matter lesion load, after adjusting for confounding factors. Simple mediation analyses showed that systolic blood pressure (SBP) or diastolic blood pressure (DBP) mediated -3.83% or -2.66% of the association between PAC and white matter lesion load, respectively. In stratified analyses, there was no evidence of subgroup heterogeneity concerning the change in the risk of WMLs (p > 0.05 for interaction for all). Conclusion: Higher PAC, especially in PAC >17.26 ng/dl, increased the risk of WMLs. PAC was positively associated with white matter lesion load independent of SBP or DBP.