Autonomous Aldosterone Secretion Research Articles

EXPLORATION OF SCREENING FOR PRIMARY ALDOSTERONISM BY IMMUNOHISTOCHEMISTRY IN PATIENTS WITH ADRENAL SURGERY IN CHINESE

Objective: Primary aldosteronism (PA) is common secondary hypertension, however, the screening rate for PA is not entirely satisfactory. This study aimed to use immunohistochemical staining for retrospective analysis of screening for PA in patients with adrenal surgery in Chinese to improve the screening rate of PA. Design and method: A total of 101 patients who were diagnosed with adrenal tumors and treated with adrenalectomy were collected. Immunohistochemical staining for anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies was performed on postoperative specimens. Analysis of staining results according to the expert consensus on the histopathology of PA. Results: Of the 101 patients included, 25 (24.75%) patients had completed secondary hypertension screening before surgery. Of the remaining 76 (75.25%) patients, immunohistochemical staining was identified in 13 patients (12.87%) with PA and 4 patients (3.96%) with autonomous secretion of cortisol. Only APM or MAPM was seen in 42 patients (41.58%). APM and MAPM were used as a potential diagnostic basis leading to PA, and functional lesions were observed in postoperative pathology in 83.17% of patients. Still, 16.83% of patients did not show clear functional histopathology on pathological staining. The overall incidence of APM and MAPM was 64.36%. Increased prevalence of APM and MAPM in patients older than or equal to 50 years old compared to patients younger than 50 years old (67.14% versus. 58.06%) and in female patients compared to males (77.78% versus. 42.11%). There without a significant difference between different ages (χ2 = 0.772, P = 0.380) but there was a significant difference between genders (χ2 = 13.149, P < 0.001). Conclusions: The screening rate of PA before adrenalectomy was less than 1/4. More than 40% of patients had pathologically confirmed APM or MAPM without systematic PA screening. Meanwhile, 16.83% of patients undergoing adrenal surgery had no clear functional histopathological manifestations. The problem of inadequate screening for PA still exists. Immunohistochemistry by anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies is an important tool in the pathological diagnosis of PA and will help identify potential autonomous secretion of aldosterone and guide improved screening for PA.

Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study

Background and AimsPrimary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD).MethodsWe included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship.ResultsIn whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy.ConclusionsPrimary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

Redefining primary hyperaldosteronism as "The Syndrome of Inappropriate Aldosterone Secretion (SIALDS)": A common but unrecognized cause of hypertension.

The current screening and diagnostic recommendations for detecting Primary Hyperaldosteronism (PHA) focus on diagnosing the more severe and overt instances of renin-independent aldosterone production. However, milder forms of autonomous aldosterone secretion have been demonstrated to exist below the diagnostic thresholds of current PHA guidelines, and associate with clinically relevant cardiovascular risk. PHAencompasses a spectrum of renin independent aldosterone production, progressing from a subclinical state in normotensives to a full-blown clinical syndrome representing the resistant hypertension population. The authors propose the Syndrome of Inappropriately Elevated Aldosterone Secretion (SIALDS) concept as a potential new paradigm for understanding and diagnosing PHA and expanded diagnostic approach to improve early detection even in well-controlled hypertension. The authors also delve into the impact of treatments, including mineralocorticoid receptor antagonists and emerging aldosterone synthase inhibitors. Furthermore, The authors outline future research directions, proposing clinical trials to investigate the long-term identification and treatment outcomes of SIALDS.

Problems in the diagnosis of secondary arterial hypertension of adrenal origin

Primary hyperaldosteronism is the leading cause of secondary arterial hypertension of adrenal origin. Its prevalence is underestimated. This leads to late diagnosis, although a timely diagnosis can achieve a complete cure for the patient, ensure control of blood pressure and avoid the development of complications. The article discusses the prevalence of primary hyperaldosteronism, its etiology and pathogenesis, the mechanisms of formation of autonomous secretion of aldosterone, including with the combined production of cortisol. The main clinical effects of aldosterone hypersecretion, its role in the formation of complications in the cardiovascular system and metabolic control are discussed. The assessment of the main clinical effects of aldosterone hypersecretion and its role in the formation of complications from the cardiovascular system and metabolic control is given. The authors remind about risk groups in which screening should be carried out, about the stages of a diagnostic search for suspected primary hyperaldosteronism. For the primary test, a preliminary assessment of the level of plasma potassium is necessary, and if hypokalemia is detected, its correction. If the result of the primary test is false negative, retesting will be carried out with the transfer of patients to antihypertensive drugs with minimal effect on the renin-angiotensinaldosterone system. It is important to remember that confirmatory sodium loading tests are contraindicated in some patients. Computed tomography with contrast in combination with selective venous blood sampling in patients are the most significant methods for the topical diagnosis of primary hyperaldosteronism. The choice of treatment method and its effectiveness depend on their results.

FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Abstract Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

FRI143 Serum Aldosterone Levels Predict Decline In Renal Function After Unilateral Adrenalectomy For Primary Aldosteronism

Abstract Disclosure: M.A. Stumpf: None. N.L. Queiroz: None. V.C. Souza: None. A.W. Maciel: None. G.F. Fagundes: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. M.A. Pereira: None. A. Pio-Abreu: None. L.A. Bortolotto: None. A. Latronico: None. M.B. Fragoso: None. L.F. Drager: None. B.B. Mendonca: None. M.Q. Almeida: None. Background: Primary aldosteronism (PA) is a very prevalent disease, characterized by an autonomous aldosterone secretion. Unilateral PA accounts for approximately 40% of the cases and is preferentially treated with surgery. Several studies reported decrease in renal function following unilateral adrenalectomy, but the risk factors associated with this decline remain to be better elucidated. Aim: Our aim was to investigate predictive factors of the decrease in renal function after unilateral adrenalectomy for PA. Methods: We retrospectively evaluated 89 PA patients submitted to unilateral adrenalectomy. Serum aldosterone, direct renin concentration, estimated glomerular filtration rate (eGFR), and electrolytes were determined at the pre-operative period and at 1 week, 1, 3 and 6 months (m) after unilateral adrenalectomy. The primary endpoint was the DELTAeGFR (eGFR after surgery at different times – eGFR before surgery). Results: Thirty-seven patients (41.6%) were men and 52 (58.4%) were women, with a median age of diagnosis of 49 years (range, 20 to 74 years). At diagnosis, the median aldosterone and renin levels were 29.8 ng/dl (7.3 - 217) and 4 μIU/mL (4 – 8.2), respectively. Hypokalemia at diagnosis was evidenced in 75 out of 89 (84.3%) of the patients. Unilateral PA was confirmed in 78 out of 89 cases (87.6%) by biochemical cure after adrenalectomy. The mean pre-operative creatinine and eGFR were 1.14 ± 0.48 mg/dL and 53.5 ± 17.1 mL/min, respectively. After adrenalectomy, the DELTAeGFR was −6.7 ± 12.1 mL/min at 1 week (p= 0.001), 0.17 ± 10 mL/min at 1m (p= 0.91), −2 ± 8.7 mL/min at 3m (p= 0.13) and −1.8 ± 10.9 mL/min at 6m (p= 0.24). Interestingly, aldosterone levels at diagnosis were significantly associated with the DELTAeGFR at 1 week (p= 0.024). PA patients with aldosterone levels &amp;gt;50 ng/dL (n= 13) at diagnosis presented a higher deterioration in renal function at 1 week when compared to those with aldosterone &amp;lt;50 ng/dL (n= 76) (αeGFR −12 ± 8.6 mL/min vs. −5.9 ± 12.5 mL/min, respectively; p= 0.032). Moreover, the patients with hypoaldosteronism (aldosterone &amp;lt;5 ng/dl) at 1 week had a lower decrease in renal function (DELTAeGFR −4.4 ± 12mL/min (n= 41) vs. −9.9 ± 11.6 mL/min (n= 42), respectively; p= 0.014) and lower levels of aldosterone at diagnosis (31.5 ± 21.1 ng/dL vs. 50.4 ± 44.4 ng/dL, respectively; p= 0.008). The post-operative decline in renal function did not correlate with age, hypokalemia, number of anti-hypertensive medications at diagnosis, immediate pre-operative and post-operative renin, and hypertension remission after surgery. Conclusion: The renal function decreased precociously after adrenalectomy but returned to basal levels after 1m. Aldosterone levels at diagnosis and at 1 week after surgery were significantly associated with decline in renal function. Support: This work was supported by the Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6. Presentation: Friday, June 16, 2023

FRI135 Differential Expression Of Circulating MicroRNAs In Primary Aldosteronism: Potential Biomarkers For Improved Diagnosis

Abstract Disclosure: S. Lamprou: None. S.M. MacKenzie: None. J.D. McClure: None. S. Robertson: None. A. Riddell: None. J.C. van Kralingen: None. A. Gimenez-Roqueplo: None. P. Reel: None. S. Reel: None. G. Assié: None. A. Laurence: None. F. Beuschlein: None. G. Rossi: None. J. Deinum: None. M. Reincke: None. G. Eisenhofer: None. E. Jefferson: None. M. Zennaro: None. E. Davies: None. Primary Aldosteronism (PA) is the most common endocrine hypertension subtype, caused by autonomous aldosterone secretion. While readily treatable, accurate diagnosis of PA – particularly its differentiation from primary hypertension (PHT) – is a complex and protracted process that can entail delays in effective treatment and lead to more severe comorbidities. Given the established role of microRNAs (miRNA) in regulating aldosterone biosynthesis, we hypothesize that circulating miRNAs are potentially viable biomarkers for PA that could inform more accurate and rapid diagnosis. To detect changes in circulating miRNA profiles specific to PA, we analyzed plasma levels of 172 selected microRNAs in a retrospectively-generated cohort of PHT (n=111) and PA patients (n=109). The dataset consisted of ΔCt values for each miRNA (normalized to multiple endogenous miRNAs), as determined by real time RT-qPCR assay. Two-sample t-tests were used to assess whether the means of the two disease groups are equal, corrected using False Discovery Rate (FDR; significance level q &amp;lt; 0.05). Ingenuity Pathway Analysis software (QIAGEN) was employed to analyze the miRNAs bioinformatically and identify mRNA targets involved in blood pressure regulation. Pathway analysis was performed to discover associations between PA and differentially-expressed miRNAs. We identified 83 circulating microRNAs that showed significant differential expression: 27 were upregulated and 56 downregulated in PA relative to PHT. The upregulated miRNA demonstrating the greatest fold change was hsa-miR-451a (FC:1.8, q=0.001), while the most downregulated was hsa-miR-409-3p (FC:0.5, q=0.001). Bioinformatics analysis predicted several dysregulated miRNAs to target mRNAs in PA-related pathways. For example, the most upregulated miRNA, hsa-miR-451a, is predicted to target mRNAs in biochemical pathways relevant to PA pathophysiology, including SGK1 and MAP3K1. SGK1 contributes to the signaling cascade induced by the mineralocorticoid receptor-aldosterone complex that stimulates Na+ reabsorption in the kidney, while MAP3K1 participates in the Renin-Angiotensin system, a key regulator of aldosterone secretion, as part of a signaling cascade that leads to the activation of the AP1 complex in the nucleus. In addition to hsa-miR-451a, other differentially-expressed miRNAs were also revealed to target multiple mRNAs with direct and indirect connections to PA. In summary, analysis has identified miRNAs that are significantly differentially expressed in the plasma of PA patients compared to PHT patients, indicating promise for a biomarker-based approach to PA diagnosis utilizing distinctive circulating microRNA signatures. Further analysis is now being conducted to validate our findings in an independent population of hypertensive patients. Presentation: Friday, June 16, 2023

Left Laparoscopic Transperitoneal Adrenalectomy for Aldosteronoma

Primary hyperaldosteronism refers to the autonomous secretion of the hormone aldosterone from the adrenal gland, resulting in low renin levels. This usually occurs in individuals between the ages of 30 to 50 years old. The majority of these cases are caused either by a solitary, functioning adrenal adenoma or aldosteronoma (70%) or by idiopathic bilateral hyperplasia (30%). Other uncommon causes include adrenal carcinoma and familial hyperaldosteronism. Patients typically present with hypokalemia and long-standing hypertension that is difficult to control despite multi-drug therapy; nevertheless, further tests are required for diagnosis. An elevated plasma aldosterone level with a suppressed plasma renin level is strongly suggestive of the diagnosis. Once confirmed, further evaluation should be directed toward determining if the cause is a unilateral aldosteronoma or bilateral adrenal hyperplasia. This is done through imaging studies and adrenal vein sampling. Unilateral aldosteronoma is best managed by adrenalectomy, with the laparoscopic approach being the preferred method. Bilateral adrenal hyperplasia is often best treated medically, because only 20%–30% benefit from surgery. Here, we present the case of a 48-year-old woman who had long-standing hypertension and hypokalemia and was found to have hyperaldosteronism and low renin levels. A CT scan showed a small mass in the left adrenal gland, and adrenal vein sampling showed higher levels of aldosterone on the left side than on the right, confirming a unilateral aldosteronoma. Laparoscopic access was gained, the adrenal gland was exposed, dissected by controlling the periadrenal tissues with the harmonic scalpel, the adrenal vein was then ligated, and the adrenal gland was removed.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses

BackgroundRenin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. MethodsWe cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. FindingsIn EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. InterpretationAmong patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes.

RAS-challenge as a first-look test for detection of primary aldosteronism in patients with treatment-resistant hypertension

PurposePrimary aldosteronism (PA), characterised by low-renin hypertension, confers a high cardiovascular risk and is the most common cause of secondary hypertension, with an increased prevalence in patients with treatment-resistant hypertension. However, it is estimated that only a small percentage of affected patients are identified in routine clinical practice. Inhibitors of the renin-angiotensin system cause an increase in renin levels in patients with intact aldosterone regulation, and inadequate low renin with concurrent RAS inhibition (RASi) may therefore indicate PA, which could serve as a first look screening test for selection for formal work-up.MethodsWe analysed patients between 2016–2018 with treatment-resistant hypertension who had inadequate low renin in the presence of RASi (i. e. at risk for PA) and who were offered systematic work-up with adrenal vein sampling (AVS).ResultsA total of 26 pts were included in the study (age 54.8 ± 11, male 65%). Mean office blood pressure (BP) was 154/95 mmHg on 4.5 antihypertensive drug classes. AVS had a high technical success rate (96%) and demonstrated unilateral disease in the majority of patients (57%), most of which (77%) were undetected by cross-sectional imaging.ConclusionIn patients with resistant hypertension, low renin in the presence of RASi is a strong indicator for autonomous aldosterone secretion. It may serve as an on-medication screening test for PA to select for formal PA work up.

Adrenal tumors: diagnostics, perioperative management and surgical treatment

Space-occupying lesions of the adrenal glands are one of the most frequent tumors; however, only a fraction of approximately 20% need further diagnostics and treatment. The diagnostic standard is native computed tomography (CT). For larger tumors and those that cannot be clearly classified as benign, the supplementary radiological modalities magnetic resonance imaging (MRI), contrast CT and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) should be used. Adrenal gland neoplasms can be hormone-active or hormone-inactive. The most important hormone-active adrenal gland neoplasms are those with autonomous cortisol secretion and autonomous aldosterone secretion as well as pheochromocytomas. Several laboratory tests are available each for the respective hormone activity. The indications for surgery are dependent on the dignity, size and hormone activity. Minimally invasive surgical techniques have become more important due to advantages such as lower blood loss; nevertheless, open surgery is still indispensable for large suspected tumors. Care must be taken preoperatively and postoperatively, particularly in cases of hormone-active tumors.

PS-R07-3: BILATERAL ADRENAL TUMORS IN A PATIENT WITH PRIMARY ALDOSTERONISM CONCURRENT WITH CUSHING'S SYNDROME: A CASE REPORT.

Background: Both primary aldosteronism (PA) and Cushing's syndrome (CS) cause hypertension. It is known that PA can be complicated with CS, but cases with both bilateral PA and unilateral CS are rare. Case presentation: A 65-year-old male patient was treated on 10 mg of amlodipine and 2 mg of doxazosin for hypertension from 6 years ago and his blood pressure was about 150/90 mm Hg on average. Because he gained 10 kg of weight over the last 6 months, he visited his primary physician. He had moon face and central obesity, and his blood examination showed the high concentrations of adrenal hormones, i.e., plasma aldosterone concentration (PAC) was 180 pg/mL and plasma renin activity (PRA) was 0.9 ng/mL/h (aldosterone-renin ratio (ARR) was 200.2), cortisol was 11.1 mcg/dL and adrenocorticotropic hormone was undetectable. The twenty-four-hour urine test showed that the greater secretion of adrenal hormones, i.e., aldosterone was 21.4 mcg/day, free cortisol was 148.5 mcg/day (sodium was 190 mEq/day). The computed tomography scan showed bilateral adrenal tumors (37 mm on the left and 8 mm on the right, respectively). The captopril challenge test, the furosemide stress test, and the 1 mg and 8 mg dexamethasone suppression tests were conducted, and he was diagnosed with both PA and CS. By adrenal scintigraphy using 131I-adosterol, high accumulation was detected in the left adrenal gland, whereas there was no accumulation in the right adrenal gland. Hence, the tumor of the left adrenal gland was likely a cortisol-secreting adrenocortical tumor. Furthermore, super-selective adrenal venous sampling indicated autonomous aldosterone secretion from bilateral adrenal glands. The patient underwent laparoscopic left adrenalectomy and the hypercortisolism was corrected. He lost 10 kg of weight 1 year after the surgery. PA remained as indicated by the blood test showing that PRA was 1.2 ng/mL/h, PAC was 347 pg/mL (ARR was 289.2). He is treated with 5 mg of esaxerenone, and his blood pressure is 130/70 mmHg on average. Conclusion: Adrenal venous sampling was able to determine laterality of PA with coexisting CS.

Autonomous Aldosterone Secretion in Patients with Adrenal Incidentaloma.

In recent years, research has emphasized the significance of mild clinical and biochemical presentations of primary aldosteronism (PA) that do not meet current diagnostic criteria of the syndrome. In this study, we assessed the prevalence of autonomous aldosterone (Ald) secretion (AAS), defined as a positive (&gt;1.2 ng/dL/mIU/L) Ald-to-renin ratio (ADRR) combined with unsuppressed Ald (&gt;4 ng/dL), and its associations with blood pressure (BP), cardiac function, and common carotid artery (CCA) intima-media thickness (IMT) in patients with incidentally discovered adrenal adenomas (AI), who were either normo- or hypertensive but had no other cardiovascular disease. Among 332 AI patients hospitalized between November 2018 and December 2019, 63 study participants were recruited (26 normo- and 37 hypertensive), who underwent hormonal examinations, 24 h ambulatory BP measurement, transthoracic echocardiography, and CCA IMT assessment without altering chronic medications. AAS was found in approximately 25% of subjects (seven normo- and nine hypertensive); urinary aldosterone excretion (UAldE) exceeded 10 ug/day in none of the subjects. The left ventricular mass index correlated positively with UAldE in non-diabetic patients (n = 50), and negatively with renin in those without beta blocker therapy (n = 38). The study shows that a pragmatic approach to hormonal assessment (no chronic therapy modification) may reveal patients with AAS. Screening for this subclinical PA presentation is probably more effective with a permissive ADRR than UAldE in such a setting.

#1321314: Primary Hyperaldosteronism Diagnosed in a 58-Year-Old Male with Longstanding Hypertension and Hypokalemia: A Case Highlighting the Importance of Early Screening and Appropriate Care of Primary Aldosteronism for Longstanding Resistant Hypertension and Hypokalemia

Primary aldosteronism (PA) is caused by autonomous secretion of aldosterone by the adrenal glands. PA is the most common cause of secondary hypertension and accounts for about 20% of cases among patients with resistant hypertension.

Abstract #1180135: Prolactinoma associated with Primary Hyperaldosteronism: ¿Is there a connection between the two entities?

Prolactinomas are the most common type of pituitary tumor. Patients presents with hyperprolactinemia associated with symptoms and signs of hypogonadism and galactorrhea. The primary hyperaldosteronism (PA) is an overlooked cause of hypertension, characterized by autonomous secretion of aldosterone. The coexistence of these two syndromes has been infrequently reported in the literature. We present a case of coexisting prolactinoma-PA.

Primary aldosteronism: A consequence of sugar and western Diet?

Primary aldosteronism is the most frequent cause of secondary hypertension. Here we present the hypothesis that the increasing incidence of primary aldosteronism is a consequence of chronic aldosterone stimulation from present day lifestyle and dietary conditions. We review epidemiological and pathophysiological evidence supporting the role of obesity, insulin resistance, hyperlipidemia, obstructive sleep apnea, and western style diet in the chronic stimulation of aldosterone secretion, with a special focus on the role of fructose in stimulating adrenocorticotropic hormone and angiotensin II expression. Sustained stimulation of clusters of aldosterone secreting cells in normal adrenal glands harboring gene mutations of aldosterone synthase and adrenocorticotropic hormone receptor would represent second-hits that eventually result in autonomous aldosterone secretion and primary aldosteronism.

Correction: Autonomous Aldosterone Secretion as a Subclinical Form of Primary Aldosteronism: Pathogenesis and Clinical Significance.

Correction: Autonomous Aldosterone Secretion as a Subclinical Form of Primary Aldosteronism: Pathogenesis and Clinical Significance.

Autonomous Aldosterone Secretion as a Subclinical Form of Primary Aldosteronism: Pathogenesis and Clinical Significance.

In recent years, a substantial prevalence of primary aldosteronism (PA) has been demonstrated in both normotensive and mildly hypertensive cohorts. Consequently, a classic presentation of the syndrome, i. e. moderate-to-severe and resistant hypertension with concomitant hypokalemia, should be considered a tip-of-the-iceberg phenotype of a wide PA spectrum. Its entire range encompasses the non-classic clinical forms of mild hypertension and prehypertension but also several biochemical presentations, including patients who meet PA screening and confirmation test criteria, as well as those with either of them and those with other parameters indicating mineralocorticoid excess. In the current review, research insights on the pathogenetic background and clinical significance of autonomous aldosterone secretion (AAS) are presented, which is defined as a constellation of either: 1) normotension, normokalemia, a positive PA screening (high aldosterone-to-renin ratio) and/or confirmation test, or 2) hypertension, normokalemia and a positive PA screening but negative confirmation test. For this purpose, a literature search of the PubMed database was conducted. Advances in immunohistochemistry and genetic sequencing of isolated adrenal cells are provided as probable morphologic basis of the wide range of aldosterone secretion autonomy. Also, the role of corticotropin as an aldosterone secretagogue is discussed. To date, clinical studies depict consequences of subclinical PA phenotypes, such as increased mortality and risk of developing hypertension, impaired arterial and kidney function, association with metabolic syndrome and age, as well as osteoporosis.