Aldosterone Hypersecretion Research Articles

MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma.

The pathophysiology of aldosterone-producing adenomas (APAs) has been intensively investigated using genetic and epigenetic approaches. However, the role of miRNAs in APA is not fully understood. The present study profiled miRNAs in APAs as an exploratory approach to elucidate their pathophysiological roles in APAs. Tissues of APAs and other adrenocortical adenomas were obtained from patients who underwent adrenalectomy. Candidate miRNAs differentially detected from samples were examined by whole miRNA sequencing. The expression of candidate miRNAs in APA tissues were further validated by real-time quantitative polymerase chain reaction (qPCR). Further, differential miRNA expression between APAs with and without KCNJ5 somatic mutations was examined. Prediction of miRNA target genes was performed by bioinformatics analysis. For specific miRNAs, correlation analysis between the levels of their target genes and CYP11B2 was analyzed in APA tissues. Our study determined differential expression of six miRNAs in APA or APA with KCNJ5 mutations. We further demonstrated that miR299 levels were negatively correlated with mRNA levels of CACNB2, which encodes the beta-subunit of the L-type calcium channel. Additionally, we found significant correlations among miR299, CACNB2, and CYP11B2 levels in APA tissues. Our study suggests the possible pathophysiological involvement of specific miRNAs in calcium signaling and aldosterone hypersecretion in APAs. Further studies, including in vitro analyses, are required to clarify these findings.

Computed tomography scan can be misleading in the lateralisation of aldosterone excess

SummaryPrimary aldosteronism (PA) is characterised by aldosterone hypersecretion and represents a common cause of secondary hypertension. During diagnostic evaluation, it is essential to determine the aetiology of PA since the treatment of unilateral and bilateral disease differs significantly. Adrenal vein sampling (AVS) has been implemented as a gold standard test for the diagnosis of PA subtype. However, due to the AVS complexity, costs and limited availability, many patients with PA are being treated based on the computed tomography (CT) findings. In this article, we present two patients with discrepant CT and AVS results, demonstrating that AVS is the only reliable method for localising the source of aldosterone excess.Learning points:CT is an unreliable method for distinguishing aldosterone-producing adenoma (APA) from bilateral adrenal hyperplasia (BAH).CT can be misleading in defining lateralisation of the aldosterone excess in case of unilateral disease (APA).AVS is the gold standard test for defining the PA subtype.

SAT-052 Comparison of Echocardiographic Parameters between Pre- and Post-Adrenalectomy in Patients with Primary Aldosteronism

Introduction: Primary aldosteronism (PA), characterized by a hypersecretion of aldosterone from the adrenal gland, increases the risks of cardiovascular disease. However, there is limited report on the changes of echocardiographic parameters after adrenalectomy in patients with PA. This study aimed to assess the multiple changes of echocardiographic parameters, including left atrial (LA) enlargement, diastolic dysfunction, left ventricular (LV) systolic function, and LV hypertrophy, pre- and post-adrenalectomy. Methods: In a retrospective cohort study, we analyzed a total of 122 patients with aldosterone-producing adenoma who underwent unilateral adrenalectomy from 2009 to 2016. All patients were diagnosed with unilateral hyperaldosteronism on the basis of segmental adrenal venous sampling (S-AVS). We excluded patients with a history of myocardial infarction, atrial fibrillation, or bilateral hyperaldosteronism. Echocardiography was performed before and 1-year after adrenalectomy and we evaluated multiple echocardiographic parameters. Results: After surgery, blood pressure, plasma aldosterone concentration and 24-hour urinary aldosterone excretion declined significantly (all P < 0.001). In echocardiography, LA diameter (LAD) decreased significantly (34.3 [30.9-37.5] to 33.8 [30.5-36.0] mm; P = 0.001). Early diastolic filling velocity to septal early diastolic mitral annular tissue velocity ratio tended to decrease (8.25 [6.99-9.58] to 7.9 [6.8-9.4], P = 0.22). LV diastolic internal dimension (48.3 [45.3-51.3] to 46.8 [42.6-49.5] mm), LV posterior wall thickness (8.5 [7.5-9.4] to 7.9 [7.4-9.0] mm), and LV mass index (LVMI) (101.17 [84.3-123.2] to 87.4 [77.0-103.2] g/m2) decreased significantly (all P < 0.001). Ejection fraction, fractional shortening, cardiac index did not change significantly. The most influencing factors to changes in LAD and LVMI were pre-operative values of each echocardiographic parameter. Conclusion: Our results indicate that correction of hyperaldosteronism by adrenalectomy improves LA enlargement and LV hypertrophy in patients with aldosterone-producing adenoma. The improvement effects on these parameters may be exerted depending on pre-operative abnormality. Adrenalectomy could be an effective treatment for decreasing risks of cardiovascular disease by improving blood pressure and cardioprotective effect.

SUN-366 The Optimal Cutoff Value for Basal Plasma Aldosterone Concentration Suspected as Primary Aldosteronism Distributed According to Aldosterone-Renin Ratio and Confirmatory Tests Response

Aldosterone/renin ratio (ARR) >200 [(pg/mL)/(ng/mL/hr)] is a widely accepted threshold to screen for primary aldosteronism (PA) (1). Because using ARR as a sole index leads to excessive inclusion of cases with low renin essential hypertension, it may be desirable to combine ARR with a minimum plasma aldosterone concentration (PAC) value to increase diagnostic accuracy, but currently there is no consensus on the minimum PAC value. Therefore, we carried out a single-center, retrospective study to investigate optimal PAC cutoff to be used with ARR >200. The subjects were 385 individuals (240 female and 145 male) with ARR >200 who underwent PA screening tests between 2010 and 2015. They were diagnosed according to the Japan Endocrine Society guideline (2) with either PA or essential hypertension (EH). The optimal cutoff value for baseline PAC that best distinguished between PA and EH was calculated. Of the 385 subjects, 297 were diagnosed with PA and 88 with EH. Of 194 PA patients who underwent adrenal venous sampling, 141 exhibited aldosterone hypersecretion from both adrenal glands, and 53 were diagnosed with aldosterone-producing adenoma (APA) on the basis of adrenalectomy. There was no difference between the PA (n = 194) and EH (n = 88) groups in terms of age, body mass index, or glucose and lipid profiles. Receiver operating characteristic curve analysis found that the optimal baseline PAC for distinguishing between PA and EH was 171 pg/mL, which provided a sensitivity of 0.75 and a specificity of 0.65 (area under the curve 0.718 and 95% confidence interval 0.656-0.780). Baseline PAC was ≥171 pg/mL for all 53 subjects with APA (minimum 171 pg/mL, maximum 943 pg/mL, and median 341 pg/mL), and if the cutoff value for baseline PAC is set at 171 pg/mL, it is unlikely that significant cases of APA will be overlooked in PA screening using ARR >200. Combining PAC ≥171 pg/mL with ARR >200 increases diagnostic accuracy for PA without compromising APA detection. Reference: (1)Hiramatsu et al., Arch Intern Med. 1981 Nov;141(12):1589-93. (2) Nishikawa et al., Endocr J. 2011;58(9):711-21.

SUN-044 Methylation Status and Gene Expression of Steroidogenic Enzymes in Benign Adrenocortical Tumors

DNA methylation has been recognized as a putative regulatory mechanism for CYP11B2 in primary hyperaldosteronism. We aimed to investigate the DNA methylation and the expression of a panel of genes encoding several enzymes involved in steroidogenesis in adrenocortical benign tumors. We collected a total of 60 adrenocortical tissues, including 9 non-functioning adrenal adenomas, 9 adenomas associated with autonomous cortisol secretion, 17 adenomas associated with Cushing’s syndrome, 13 Conn’s adenomas and 12 tissues derived from adrenal gland adjacent to the Conn’s adenomas. Non-functioning tumors and autonomous cortisol secretion were defined according to cortisol levels after 1 mg dexamethasone suppression test ≤ or > 50 nmol/L, respectively. The DNA methylation level of CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DHCR24, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO was evaluated by quantitative Bisulfite Next Generation Sequencing (bisulfite-NGS). Bioinformatic analysis was performed in a GalaxyProject environment and processed by BSPAT (Bisulfite Sequencing Pattern Analysis Tool). Spearman correlation coefficients were calculated using IBM SPSS 21 (IBM). CYP11B1, CYP11B2, CYP17, CYP21, STAR and β-actin gene expressions were examined by quantitative Real-Time PCR using a Sybr Green Assay kit (Thermo Fisher Scientific). The equation 2−ΔΔCt was used to calculate the fold changes in gene expression between the categories of samples. CYP11B2 was significantly hypomethylated in Conn’s adenoma, when compared to other adrenal tissues (P<0.001). No difference in methylation status was found among groups for the remaining genes. CYP11B2 mRNA levels were significantly higher in Conn’s adenoma than in the remaining adrenal tissues (P=0.001). CYP21 mRNA was significantly higher in all but Conn’s adenomas, when compared to normal adrenal tissues (P<0.001). Overall, we found a negative correlation between CYP11B2 expression and DNA methylation (rho= -0.379; P=0.003). DNA methylation seems to be a pivotal regulatory mechanism for CYP11B2 expression. It is feasible that epigenetic mechanisms may be responsible for aldosterone hypersecretion in Conn’s adenoma.

SAT-521 Changes in Multiple Bone Metabolism Markers after Adrenalectomy in Patients with Aldosterone Producing Adenoma

<Background > In primary aldosteronism (PA), it is reported that secondary hyperparathyroidism (SHPT) is caused by increased urinary Ca excretion due to excessive aldosterone, which may decrease bone mineral density and increase fracture risk. However, there have been few reports that evaluated changes in bone metabolism markers in detail before and after the treatment for PA. In this retrospective study, we evaluated changes in multiple bone metabolism markers before and after adrenalectomy. <Methods> We analyzed 16 patients who underwent adrenalectomy for unilateral aldosterone-producing adenoma (APA) in our hospital from April 2009 to November 2017 and compared various bone metabolism markers before and after surgery. All patients were diagnosed with unilateral hyperaldosteronism by segmental adrenal venous sampling. Patients with bilateral hyperaldosteronism and bone disease were excluded. We compared changes in levels of serum Ca, 24-hour urinary Ca excretion (u-Ca), intact parathyroid hormone (iPTH), tartrate-resistant acid phosphatase 5b (TRACP-b5), bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin (ucOC) before and one year after surgery. <Results> Sixteen patients consisted of 8 males and 8 females (Mean age =49.6 years old, BMI =23.7 kg/m2, hypertension duration =10.9 years, blood pressure =135/84 mmHg, eGFR =86.6 mL/min/1.73 m2). After surgery, aldosterone hypersecretion improved markedly (plasma aldosterone (PAC); 278.4 ± 167.5 to 96.9 ± 47.1 pg/mL, urinary aldosterone; 28.6 ± 22.7 to 5.6 ± 3.9 μg/day). Significant increase in serum Ca (8.74 ± 0.24 to 9.31 ± 0.80 mg/dL, P < 0.001) and decreases in u-Ca (0.23 ± 0.10 to 0.09 ± 0.07 g/day, P = 0.002) and iPTH (86.7 ± 40.8 to 54.4 ±16.3 pg/mL, P < 0.001) were observed. In addition, significant decreases in TRACP-b5 (373.0 ± 180.1 to 211.9 ± 101.2 mU/dL, P < 0.001), BAP (16.6 ± 7.06 to 10.8 ± 3.73 μg/L, P < 0.001), and ucOC (7.56 ± 5.0 to 4.04 ± 2.3 ng/mL, P = 0.004) levels were observed. The change in iPTH had significant positive correlation with the change in PAC (r = 0.55, P = 0.026), while it had no correlation with the change in u-Ca. <Conclusion> The correction of hyperaldosteronism by adrenalectomy decreased urinary Ca excretion, iPTH level, and bone tune over. In addition, our results suggest that the increase in iPTH was caused by hyperaldosteronism, independent from the excess in urinary calcium excretion.

Influence of Adrenal Venous Sampling on Management in Patients with Primary Aldosteronism Independent of Lateralization on Cross-Sectional Imaging

Patients with primary aldosteronism undergo imaging of the adrenal glands after confirmation of the disease. Adrenal venous sampling (AVS) is a useful adjunct to imaging, and advocates believe that AVS should be performed before surgical management. Others argue that patients with unilateral lesions on imaging do not require AVS. Although AVS accuracy has been established, few studies have evaluated how AVS alters management. Our study aimed to determine how AVS affected management of these patients. Patient data were collected retrospectively from the electronic medical records at a single institution. Patients aged 18 years or older who underwent AVS with successful adrenal vein cannulation from 2007 to 2016 were included. The laterality of AVS was compared with laterality of preprocedural imaging for each patient. The management plan before AVS was determined by laterality on preprocedural imaging. The primary outcomes were management of primary aldosteronism, change in management compared with the plan before AVS, and antihypertensive medication use after therapy. Seventy-four patients had successful adrenal venous cannulation. Thirty-three (44.6%) patients had AVS lateralization that was concordant with preprocedural imaging. Forty-one (55.4%) patients had AVS lateralization that was non-concordant with preprocedural imaging. There was a change in management in 29 (39.2%) patients. Adrenal venous sampling can delineate the source of aldosterone hypersecretion, and often this is not concordant with cross-sectional imaging. We found that many patients avoided a potentially non-curative operation due to AVS. Adrenal venous sampling frequently alters the management of aldosteronomas and should be highly considered in patients before surgical intervention.

Paracrine Regulation of Aldosterone Secretion in Physiological and Pathophysiological Conditions.

Aldosterone secretion by the zona glomerulosa of the adrenal cortex is controlled by circulating factors including the renin angiotensin system (RAS) and potassium. Mineralocorticoid production is also regulated through an autocrine/paracrine mechanism by a wide variety of bioactive signals released in the vicinity of adrenocortical cells by chromaffin cells, nerve endings, cells of the immune system, endothelial cells and adipocytes. These regulatory factors include conventional neurotransmitters and neuropeptides. Their physiological role in the control of aldosterone secretion is not fully understood, but it is likely that they participate in the RAS-independent regulation of zona glomerulosa cells. Interestingly, recent observations indicate that autocrine/paracrine processes are involved in the pathophysiology of primary aldosteronism. The intraadrenal regulatory systems observed in aldosterone-producing adenomas (APA), although globally similar to those occurring in the normal adrenal gland, harbor alterations at different levels, which tend to strengthen the potency of paracrine signals to activate aldosterone secretion. Enhancement of paracrine stimulatory tone may participate to APA expansion and aldosterone hypersecretion together with somatic mutations of driver genes which activate the calcium signaling pathway and subsequently aldosterone synthase expression. Intraadrenal regulatory mechanisms represent thus promising pharmacological targets for the treatment of primary aldosteronism.

Diagnosis and treatment of primary aldosteronism: practical clinical perspectives.

Primary aldosteronism (PA), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. Confirmatory testing is indicated in most patients with positive case detection testing results. The next step is to determine whether patients with confirmed PA have a disease that can be cured with surgery or whether it should be treated medically; this step is guided by computed tomography scan of the adrenal glands and adrenal venous sampling. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low-sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at adosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements.

Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2-3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10-40% of the cases by autonomous cortisol hypersecretion, and in 1-10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients.

MiRNA-203 Modulates Aldosterone Levels and Cell Proliferation by Targeting Wnt5a in Aldosterone-Producing Adenomas.

The aberrant expression or alternation of miRNA in the pathogenesis of aldosterone-producing adenomas (APAs) is still largely unknown. We investigated the role of miRNA-203 (screened from miRNA microarrays) and elucidated its effects on the Wnt/β-catenin pathway regarding aldosterone production and cell proliferation in APAs. miR-203 expression was upregulated or downregulated by transfecting miR-203 mimics or inhibitors into primary APA cells, the human adrenocortical cell line HAC15, and C57BL/6 mice. In vitro and biochemical data were correlated with the respective clinical parameters of APAs to evaluate their clinical importance. The expression of miR-203 in human APA samples was significantly lower than that of peritumor adrenal samples. Tumoral miR-203 abundance correlated negatively with both plasma aldosterone level and tumor size in patients with APAs. miR-203 inhibitors increased aldosterone production and cell proliferation in HAC15 cells, and restoration of expression via miR-203 mimics showed decreased cell proliferation and aldosterone hypersecretion in APA cell cultures. In vivo selective inhibition of miR-203 via intra-adrenal injection of miR-203 inhibitors in mice led to a substantial increase in systolic blood pressure and plasma aldosterone levels. Additionally, the dual-luciferase reporter assay demonstrated that WNT5A is a direct target of miR-203. Furthermore, plasma Wnt5a levels in adrenal vein sampling were helpful in differentiating tumor localization, and preoperative plasma Wnt5a levels predicted the cure of hypertension after adrenalectomy. We have demonstrated that attenuated miR-203 expression in APAs increases aldosterone production and the tumorigenesis of adrenal cells by activating the Wnt5a/β-catenin pathway.

Saline suppression test parameters may predict bilateral subtypes of primary aldosteronism.

The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA) whilst adrenal vein sampling (AVS) is used to determine whether the aldosterone hypersecretion is unilateral or bilateral. An accurate prediction of bilateral PA based on SST results could reduce the need for AVS. We sought to identify SST parameters that reliably predict bilateral PA. The results from 121 patients undergoing SSTs at Monash Health from January 2010 to January 2018 including screening blood tests, imaging, AVS and histopathology results were evaluated. Patients were subtyped into unilateral or bilateral PA based on AVS and surgical outcomes. Of 113 patients with confirmed PA, 33 had unilateral disease whilst 42 had bilateral disease. In those with bilateral disease, plasma aldosterone concentration (PAC) was significantly lower post-SST, together with a significant fall in the aldosterone-renin ratio (ARR). The combination of PAC<300pmol/L and a reduction in ARR post-SST provided 96.8% specificity in predicting bilateral disease. Eighteen of 39 patients (49%) with bilateral PA could have avoided AVS using these criteria. A combination of PAC<300pmol/L and a lower ARR post-SST could reliably predict bilateral PA. An independent cohort will be needed to validate these findings.

URINARY POTASSIUM LOSS INDUCED BY HYPERALDOSTERONE SECRETION ASSOCIATED WITH DIABETES MELLITUS PREVALENCE IN HYPERTENSIVE PATIENTS

Objective: Primary aldosteronism(PA) is characterized by hypersecretion of aldosterone with increased urinary potassium(K+) excretion and hypertension. Diabetes was more frequent in PA and the association between DM and PA involved in hypokalemia. The status of low serum K+ was related to chronic urinary K+ excretion. The aim of this study was to find out whether hyperaldosterone and urinary K+ excretion could increase the risk of diabetes in patients with PA. Design and method: 790 hypertensive in-patients were enrolled from Hypertension Center of People's Hospital Of Xinjiang. DM participants included patients with known or newly-diagnosed diabetes. All of them entered a protocol for screening PA. The positive initial screening group was defined on plasma aldosterone concentration (PAC) /renin activity (ARR) > 20 ng/dL per ng/mL/h. PA group was according on ARR > 20 plus PAC > 10 ng/dL after saline infusion test. Baseline characteristics were collected including blood pressure, lipids, plasma renin activity, PAC, serum K+ and 24 h-urine K+ levels. The relationship of hyperaldosterone or urinary K+ excretion with DM was evaluated during the screening process of PA. Results: In positive screening group, 24 h-urine K+ levels or PAC associated with DM prevalence, age tertile (OR 3.173, 95%CI 1.801–5.590, p < 0.01), urinary K+ tertile(OR 2.221, 95%CI 1.251–3.942, p < 0.01), PAC tertile(OR 1.728, 95%CI 1.091–2.737, p < 0.05) and the cumulative contribution(OR 1.262, 95%CI 1.073–1.483, p < 0.01), independent of systolic blood pressure and lipids. Compared with 86 age- and sex-matched patients without PA, patients with PA had significantly higher PAC (22.3+11.9 vs 12.6+5.7, p < 0.01), lower 24 h-urine K+ levels (46.2+29.9 vs 35.9+15.2, P < 0.01), and higher DM prevalence (29.1% vs 9.3%, P < 0.01). The level of urinary K+ (52.5+17.0 vs 46.7+21.3 vs 35.7+17.7, P < 0.05) and PAC (22.4+9.9 vs 22.9+17.2 vs 12.8+5.53, p < 0.05) were different significantly among three groups with PA&DM, single PA and no-(PA&DM) match for -age and -sex in a 1:1:1 fashion. And the correlation of 24 h-urine K+ levels or PAC with DM prevalence was clear among the groups, the coefficient of correlation were 0.323 and 0.300, respectively(P < 0.01). Conclusions: Urinary potassium loss induced by hypersecretion of aldosterone associated with DM prevalence in patients with hypertension.

A short review of primary aldosteronism in a question and answer fashion

The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism

BackgroundWe report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed.Case presentationA 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection.ConclusionA clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

Diagnosis and Treatment of Primary Aldosteronism in 2017: Did We Achieve Our Goals?

For many decades primary aldosteronism (PA) was dismissed as a rare endocrine condition, but is nowadays widely accepted as the most frequent endocrine cause of hypertension, largely due to the widespread use of the aldosterone-to-renin ratio as a screening test. With a prevalence of 5% of hypertensive subjects in primary care and 10% of hypertensives in referral centers, screening strategies should be extended to designated risk populations, as suggested by several recent national and international guidelines [1] [2] [3]. Primary aldosteronism is highly prevalent in patients with sleep apnea, resistant hypertension (10–30%), and patients with hypokalemic hypertension (>60%). With a growing awareness of the cardiovascular and metabolic comorbidities of sustained aldosterone hypersecretion [4] [5] [6] [7], and the possibility of reversing these consequences through early detection and therapy [8], the diagnosis of PA should be timely.

The Latest Developments of Functional Molecular Imaging in the Diagnosis of Primary Aldosteronism.

Differentiation of unilateral from bilateral aldosterone hypersecretion is the essential step in the clinical practice of primary aldosteronism (PA). Although adrenal venous sampling (AVS) has been established as the most standard test recommended by the guideline, its invasive and technically difficult nature has facilitated the approach to develop non-invasive functioning imaging as an alternative test. Compared to the conventional adrenocortical scintigraphy with cholesterol derivatives as tracer, the first-generation imaging, both of 11C-MTO/PET and 123I-IMTO/SPECT/CT, the second-generation imaging, bind with high specificity and affinity to CYP11B enzymes and have advantages in shortening the time for obtaining specific images, reducing the radiation exposure to the patient, and resolution of the images. Because of very short half-life of 11C-MTO, 123I-IMTO has a potential for a wider application than 11C-MTO. Sensitivity of identifying an adenoma smaller than 1 cm in diameter is still a common limitation of these new functional imaging methods. The new functional imaging could be supplementary to AVS in lateralization of PA when the results of AVS are not conclusive. To be a substitute for AVS, however, it should fulfill various conditions including high selectivity and binding affinity to CYP11B2, high sensitivity in detecting small adenoma, high resolution image, reduction of radiation exposure, and general versatility. Considering the potential number of patients, cost-effectiveness of the subtype testing in the clinical practice of PA could be one of the issues of the medical expenses. Thus, development of a new non-invasive functional imaging will have a significant impact on the clinical practice of PA and hypertension.

A case of Adrenocoricotrophic hormone -independent bilateral adrenocortical macronodular hyperplasia concomitant with primary aldosteronism

BackgroundAdrenocoricotrophic hormone (ACTH) – independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome, and is characterized by bilateral adrenal hyperplasia. However, Primary aldosteronism (PA) is a relatively common adrenal disease.Case presentationA 56-year-old man who has been treated hypertension and diabetes mellitus was detected low plasma potassium level with an elevated level of plasma aldosterone concentration and bilateral adrenal swelling. Endocrinological examinations showed autonomous secretion of cortisol and aldosterone, with suppression of plasma ACTH level and renin activity. A selective adrenal venous sampling demonstrated that left adrenal gland was responsible for aldosterone hypersecretion. He was diagnosed preclinical Cushing’s syndrome due to ACTH – independent bilateral adrenocortical macronodular hyperplasia (AIMAH) associated with aldosterone producing adenoma of the left adrenal gland. A laparoscopic left adrenalectomy was performed.ConclusionThe resected adrenal specimen histologically consisted with a diagnosis of AIMAH. Moreover, tiny cell clusters positive immunostaining for aldosterone synthase was revealed. This is a rare case of AIMAH accompanied by preclinical Cushing’s syndrome and primary aldosteronism.

PP.25.26] A CASE OF SECONDARY HYPERTENSION IN A PRIMARY HEALTH CARE UNIT

Objective: To perform a diagnostic and etiological evaluation of a hypertensive patient in a primary health care unit. Design and method: Retrospective analysis of the patient's medical records. Results: A 45-year-old male presented to his new primary care physician with dermatological complains. The patient's medical history was notable for non-controlled hypertension and Osler-Weber-Rendu Disease, while his current medication included Lercanidipine 20 mg. His physical examination was notable for a blood pressure of 156/104 mmHg and a body mass index of 25 kg/m2. Dermatological complains were promptly managed, a complete cardiovascular risk stratification was performed and the patient was discharged with Ambulatory Blood Pressure Monitoring and indication to perform an analytic study in a few days. On revaluation, because the patient had sustained high blood pressure values and ECG features of left ventricular hypertrophy, a transthoracic echocardiogram and a study of secondary causes of hypertension were performed. His etiological study was notable for a diminished plasma renin activity (PRA) of 0.2 ng/ml/h, an elevated plasma aldosterone concentration (PAC) of 26 ng/dl with a plasma aldosterone-to-renin ratio of 130ng/dl and a potassium level of 3.5mmol per liter. Levels of urinary metanephrines, vanilmandelic acid and catecholamines were within normal range. Ultrasound imaging of the adrenal glands revealed a 25 mm nodular formation, most likely an adenoma. Spironolactone 25 mg was added and an abdominopelvic CT was performed which not only confirmed the findings but also revealed a 13 mm left adrenal adenoma. Currently, the patient awaits hospital management, medicated with Lercanidipine 20 mg and Spironolactone 50 mg. His serum potassium levels are normal and his blood pressure is controlled, below 140/90 mmHg. Conclusions: Primary hypersecretion of aldosterone is an underdiagnosed cause of hypertension, of growing prevalence in our society. The increased but reversible cardiovascular risk of these patients warrants a complete and exhaustive diagnostic evaluation and treatment which can and should start in a primary health care setting.

Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism.

The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.