Cause Of Secondary Hypertension Research Articles

An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying K+ Channel 4 Variant to Identify Small Molecule Modulators

Primary aldosteronism is characterised by the excessive production of aldosterone, which is a key regulator of salt metabolism, and is the most common cause of secondary hypertension. Studies have investigated the association between primary aldosteronism and genetic alterations, with pathogenic mutations being identified. This includes a glycine-to-arginine substitution at position 151 (G151R) of the G protein-activated inward rectifier potassium (K+) channel 4 (GIRK4), which is encoded by the KCNJ5 gene. Mutations in GIRK4 have been found to reduce the selectivity for K+ ions, resulting in membrane depolarisation, the activation of voltage-gated Ca2+ channels, and an increase in aldosterone secretion. As a result, there is an interest in identifying and exploring the mechanisms of action of small molecule modulators of wildtype (WT) and mutant channels. In order to investigate the potential modulation of homotetrameric GIRK4WT and GIRK4G151R channels, homology models were generated. Molecular dynamics (MD) simulations were performed, followed by a cluster analysis to extract starting structures for molecular docking. The central cavity has been previously identified as a binding site for small molecules, including natural compounds. The OliveNetTM database, which consists of over 600 compounds from Olea europaea, was subsequently screened against the central cavity. The binding affinities and interactions of the docked ligands against the GIRK4WT and GIRK4G151R channels were then examined. Based on the results, luteolin-7-O-rutinoside, pheophorbide a, and corosolic acid were identified as potential lead compounds. The modulatory activity of olive-derived compounds against the WT and mutated forms of the GIRK4 channel can be evaluated further in vitro.

Targeted multiplex proteomics for the development and validation of biomarkers in primary aldosteronism subtyping.

Primary aldosteronism (PA), a significant cause of secondary hypertension affecting ∼10% of patients with severe hypertension, exacerbates cardiovascular, and cerebrovascular complications even after blood pressure control. PA is categorized into two main subtypes: unilateral aldosterone-producing adenomas (APA) and bilateral hyperaldosteronism (BHA), each requiring distinct treatment approaches. Accurate subtype classification is crucial for selecting the most effective treatment. The goal of this study was to develop novel blood-based proteomic biomarkers to differentiate between APA and BHA subtypes in patients with PA. Five subtyping differential protein biomarker candidates (APOC3, CD56, CHGA, KRT5, and AZGP1) were identified through targeted proteomic profiling of plasma. The subtyping efficiency of these biomarkers was assessed at both the tissue gene expression and blood protein expression levels. To explore the underlying biology of APA and BHA, significant differential pathways were investigated. The five-protein panel proved highly effective in distinguishing APA from BHA in both tissue and blood samples. By integrating these five protein biomarkers with aldosterone and renin, our blood-based predictive methods achieved remarkable receiver operating characteristic (ROC) area under the ROC curves of 0.986 (95% CI: 0.963-1.000) for differentiating essential hypertension from PA, and 0.922 (95% CI: 0.846-0.998) for subtyping APA versus BHA. These outcomes surpass the performance of the existing Kobayashi score subtyping system. Furthermore, the study validated differential pathways associated with the pathophysiology of PA, aligning with current scientific knowledge and opening new avenues for advancing PA care. The new blood-based biomarkers for PA subtyping hold the potential to significantly enhance clinical utility and advance the practice of PA care.

Short- and long-term outcomes of adrenalectomy for primary aldosteronism in a single UK center: rear-mirror view

Abstract Purpose Primary aldosteronism (PA), which is the commonest cause of secondary hypertension, can be cured by unilateral adrenalectomy. We report the short-and long-term outcomes after adrenalectomy performed at a single UK center over a period of 24 years. Methods Retrospective analysis of biochemical (potassium, aldosterone, renin, and ARR) radiological (CT/MRI, AVS, and nuclear scans), and clinical (surgical complications, blood pressure, and number of antihypertensive medications) short-and long-terms outcomes in patients who underwent adrenalectomy for PA between 1998 and 2021. Standardized PASO and Clavien-Dindo criteria to assess biochemical, clinical, and surgical outcomes were used. Results A total of 82 patients were treated via adrenalectomy for PA over a 24-year period. Short-term follow-up data (within 3 months after surgery) was available for all 82 patients (M45, F37, mean age 51.7 years): 24 of them were followed up for at least 60 months (range 60 to 72 months) and 77 (93.9%) patients had laparoscopic surgery (one conversion). Seven patients had postoperative complications classified as Clavien-Dindo II (4), IIIa(1) and IVa(2). Median LOS was 2.5 days (1–12). Complete and partial clinical success was achieved in 29 and 58.3% and 41.7 and 45.8% of patients in the short and the long term, respectively. Clinical benefit was observed in 88% of patients. Complete biochemical success was achieved in 95.8% of patients in the short and the long term. Conclusion Unilateral adrenalectomy in patients with PA showed clinical benefit in 88% and achieved biochemical cure in almost all of them. Our data suggest that these benefits persisted for at least 5 years.

Multiple Treatment Strategies of Accessory Renal Artery Related Hypertension: Report of Two Cases and Literature Review.

Renovascular hypertension (RVH) is a primary cause of secondary hypertension, primarily driven by the activation of the renin-angiotensin-aldosterone system activation. Recently, growing studies suggested accessory renal artery (ARA) might also contribute to RVH. However, the treatment of ARA-related hypertension and whether to take interventional treatment lack consensus. Herein, we report two cases of ARA-related hypertension in our hospital. Imaging studies of both patients showed ARA stenosis. One patient had ARA occlusion well-compensated through tortuous collateral branches, achieving normal blood pressure by medical treatment alone. The other patient had ARA stenosis coexisted with main renal artery stenosis, and revascularization of both arteries led to a significant postoperative reduction in blood pressure. A literature review was conducted to summarize overall treatment strategies for ARA-related hypertension and clarify the relationship between ARA and hypertension. Recent research supported an association between ARA and hypertension. While medical therapy remains the first-line treatment for ARA-related hypertension, interventional procedures should be considered for patients whose blood pressure remains uncontrolled despite conservative management.

Renovascular hypertension - a primer for the radiologist.

Renovascular hypertension (RVHT) is an important cause of secondary hypertension, accounting for approximately 75% of cases. This pictorial review describes the imaging modalities used to diagnose RVHT, including ultrasound, computed tomography angiography, and magnetic resonance angiography, provides their benefits and limitations, and explores the imaging findings, diagnostic criteria, and management of multiple causes of RVHT. Atherosclerosis is the most common cause of RVHT, particularly in older individuals, while fibromuscular dysplasia is more prevalent in younger females. Less common discussed etiologies include polyarteritis nodosa, extrinsic compression, Page kidney, dissection, renal artery (RA) thrombus, and RA aneurysms. This paper also highlights the importance of recognizing anatomical variants and rare conditions that can impact diagnosis and management. While RVHT represents a minority of hypertension cases, its potential reversibility makes accurate diagnosis crucial. Treatment approaches vary based on etiology and may include medical management, angioplasty, stenting, or surgical intervention. This review aims to enhance radiologists' understanding of RVHT, facilitating improved diagnosis and patient care.

Etiology and Medication of Hospitalized Children With Hypertension: A Retrospective Study.

With the increasing incidence of hypertension in children, the lack of high-quality research data on antihypertensive drugs in pediatric patients restricts treatment options for clinicians and can lead to suboptimal outcomes. We conducted a retrospective analysis of clinical data from hospitalized pediatric patients diagnosed with hypertension and treated with antihypertensive drugs in the past 3years. The study included 203 pediatric patients (119 males and 84 females), with an average age of 8.9±4.7years (range: 0.1-17years). Clinical symptoms of hypertension were observed in 132 participants (65.0%), and the conditions in all cases were classified as primary or secondary hypertension. Renal causes (71 patients, 35.0%) and drug-induced factors (39 patients, 19.2%) were the main causes of secondary hypertension. Nifedipine (137 patients, 67.5%) was the most commonly prescribed medication, followed by captopril (84 patients, 41.4%). Multiple antihypertensive medications were prescribed to 99 participants (48.8%), and blood pressure returned to normal in 111 patients (54.7%). Hypertension-related organ damage was observed in 47 patients (23.2%). Timely diagnosis and treatment of hypertension are critical to prevent organ damage in pediatric patients. Although nifedipine was widely used in this pediatric cohort, the appropriateness of this treatment remains unclear. Emphasis should be placed on monitoring target organs affected by pediatric hypertension, and post-discharge antihypertensive treatment should include thorough follow-ups and documentation.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

Active Choice Nudge to Increase Screening for Primary Aldosteronism in At-Risk Patients.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe: 1) PA screening practices in a large, diverse health system, 2) the development of a computable phenotype for PA screening, and 3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening. A multidisciplinary team developed a multi-pronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across two primary care practices for seven months. Screening frequencies were compared to clinics not receiving the intervention. The baseline frequency of screening of eligible patients within one year was 1.4%. Higher mean systolic blood pressure (OR=1.4; p<0.001), more antihypertensive medications (OR=1.3; p=0.002), lower minimum serum potassium (OR=2.0; p=0.001), specialist care (OR=3.0; p<0.001), and Black race (OR=1.5; p=0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% versus 4.1%; p=0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the non-intervention clinics (1.8%; p<0.001). PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening.

Atherosclerotic Renal Arterial Stenosis with Multivascular Involvement in a Patient Presenting with Uncontrolled Hypertension and Cardiac Dysfunction

Renal artery stenosis (RAS) is the most common cause of secondary hypertension, with an incidence rate of 1–3% and atherosclerosis being the most common cause in 90% of the cases. The detection of atherosclerotic RAS may portend multivascular involvement; hence, a more comprehensive approach is essential. Clinical outcomes depend on renal condition and atherosclerotic burden with other coexisting cardiovascular diseases. A haemodynamically significant RAS can be considered with the onset of hypertensive crisis associated with worsening renal function and flash pulmonary oedema, known as Pickering syndrome. Despite the current controversy regarding the lack of randomised studies supporting the benefits of revascularisation over medical therapy, this may be considered in patients with RAS and Pickering syndrome. Reported here is the case of a 76-year-old woman with bilateral RAS who presented with persistent elevated blood pressure and heart failure symptoms. The patient underwent successful bilateral percutaneous transluminal renal angioplasty. Long-term monitoring requires maintaining adequate blood pressure control and renal function.

Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism.

Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism. MiRNA profiling was conducted on plasma samples from 18 patients with primary aldosteronism taken during adrenal venous sampling on an Illumina MiSeq platform. Bioinformatics and machine learning identified 9 miRNAs for validation by reverse transcription real-time quantitative polymerase chain reaction. Validation was performed on a cohort consisting of 108 patients with known subdifferentiation. A 30-patient subset of the validation cohort involved both adrenal venous sampling and peripheral, the rest only peripheral samples. A neural network model was used for feature selection and comparison between adrenal venous sampling and peripheral samples, while a deep-learning model was used for classification. Our model identified 10 miRNA combinations achieving >85% accuracy in distinguishing unilateral primary aldosteronism and bilateral adrenal hyperplasia on a 30-sample subset, while also confirming the suitability of peripheral samples for analysis. The best model, involving 6 miRNAs, achieved an area under curve of 87.1%. Deep learning resulted in 100% accuracy on the subset and 90.9% sensitivity and 81.8% specificity on all 108 samples, with an area under curve of 86.7%. Machine learning analysis of circulating miRNAs offers a minimally invasive alternative for primary aldosteronism lateralization. Early identification of bilateral adrenal hyperplasia could expedite treatment initiation without the need for further localization, benefiting both patients and health care providers.

Diagnostic and Therapeutic Approach to the Major Secondary Causes of Arterial Hypertension in Young Adults: A Narrative Review

Arterial hypertension in young adults, which includes patients between 19 and 40 years of age, has been increasing in recent years and is associated with a significantly higher risk of target organ damage and short-term mortality. It has been reported that up to 10% of these cases are due to a potentially reversible secondary cause, mainly of endocrine (primary aldosteronism, Cushing’s syndrome, and pheochromocytoma/paraganglioma), renal (renovascular hypertension due to fibromuscular dysplasia and renal parenchymal disease), or cardiac (coarctation of the aorta) origin. It is recommended to rule out a secondary cause of high blood pressure (BP) in those patients with early onset of grade 2 or 3 hypertension, acute worsening of previously controlled hypertension, resistant hypertension, hypertensive emergency, severe target organ damage disproportionate to the grade of hypertension, or in the face of clinical or biochemical characteristics suggestive of a secondary cause of hypertension. The 2023 Guideline of the European Society of Hypertension recommends starting pharmacological therapy from grade 1 hypertension (BP ≥140/90 mm Hg), with the aim of achieving BP control of less than 130/80 mm Hg. It is important to highlight that the prevalence of secondary hypertension in these patients could be underestimated, given that there is little evidence available on the management of high BP in young adults, which is why we developed this narrative review on the diagnostic and therapeutic approach to the major secondary causes of arterial hypertension in young adults.

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BackgroundPrimary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.MethodsThis prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.ResultsAt follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.ConclusionFor PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Vascular Abnormalities and Neurofibromatosis Type 1: A Paediatric Case Series.

Neurofibromatosis type 1 (NF1) is a multisystemic neurocutaneous disease caused by a heterozygous mutation of the NF1 gene that encodes neurofibromin. Complications include vascular and neurologic abnormalities such as moyamoya syndrome, a cerebrovascular disorder with progressive occlusion of the large intracranial arteries, leading to ischemic events and the formation of abnormal vascular networks. Stenosis of the renal artery is another frequent complication of neurofibromatosis type 1, and it represents the most common cause of secondary hypertension in these patients. The purpose of the article is to describe the clinical manifestations of neurofibromatosis type 1 vasculopathy in 4 patients presenting with a wide range of neurologic and reno-vascular manifestations, as well as to examine current diagnostic management and follow-up, current therapeutic options, and to discuss further perspectives in terms of screening, diagnosis, and treatment.

8401 Genetic Characterization of a Case of Primary Aldosteronism in an 11-Year-Old Girl carrying a Germline VUS of CACNA1H and a Somatic Mutation of CTNNB1

Abstract Disclosure: S. Parisien-La Salle: None. G. Van Vliet: None. G. Corbeil: None. M. Labrecque: None. M. Tétreault: None. I. Bourdeau: None. Introduction: Primary aldosteronism is a frequent cause of secondary hypertension in adults but is rare in children. We report the case and genetic studies of an 11 yo girl presenting with primary aldosteronism at puberty. Case presentation: An 11-year-old female patient was referred to the pediatric endocrinology clinic for hypertension (166/118). Her past medical history and family history were unremarkable. She reported polyuria, polydipsia and occasional headaches and abdominal pain. Her Tanner stage indicated that puberty was initiated (P2M2). An abdominal CT revealed a 9x10x11cm right adrenal mass with calcifications and a necrotic zone. On [1]8F-FDG PET/CT, the mass had an uptake of 2.9 SUVmax. Laboratory results revealed hypokalemia (K: 2.6 mmol/L [N: 3.5-4.5]) and elevated aldosterone (1712.8 pmol/L [N: 110-1330]) with suppressed renin (0.2 ng/ml/h [N: &amp;lt;5.3]). Her urinary aldosterone level was elevated (114 nmol/day [N: &amp;lt;67]). The rest of the biochemical adrenal panel was normal. Patient underwent a right adrenalectomy by laparotomy. The pathology report showed an adrenal tumor without capsular or vascular invasion. The only malignancy criterion was an area of necrosis and the ki-67% proliferation index was &amp;lt; 1%. Genetic investigations: After informed consent, the patient underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA), which were both negative except for a variant of unknown significance (VUS) that was identified in CACNA1H (c.3868G&amp;gt;A, p.Val1290Ile) with a minor allele frequency of 3.291E-5 (GnomAD). Tumor DNA was extracted after adrenalectomy from fresh frozen tissues. Somatic genetic analysis of GNAS, CTNNB1, KCNJ5, ATP1A1, ATP2B3 and CACNA1D was performed using direct Sanger Sequencing (Genome Quebec Innovation Centre) and revealed a heterozygous missence pathogenic variant in the CTNNB1 gene (c.121 A&amp;gt;G p.Thr41Ala). This mutation was absent in leukocyte DNA of the patient. Immunohistochemistry of the adrenal tumor disclosed strong cytoplasmic β-catenin staining in most tumor cells (monoclonal anti-β-catenin antibody; BD Transduction Laboratories). RNA-sequencing of patient tumor RNA was performed (Research Center CHU Québec) and compared to human adrenal total RNA (Clontech, Mountain View, CA). Pathway enrichment analysis showed activation of the Wnt signaling pathway. No variant was identified in GNAQ or GNA11 genes. However, GNRHR was upregulated compared to the control sample with a log2 fold change of 3.96 (p=0.000074). Conclusion: We present a rare pediatric case of an aldosterone producing adenoma harbouring a somatic β-catenin pathogenic variant with upregulation of GNRHR. The implication of the germline CACNA1H VUS still needs to be clarified. Presentation: 6/3/2024

8501 Adrenal Incidentaloma In A Pregnant Woman Diagnosed With Preeclampsia

Abstract Disclosure: V.P. Vargas-Abonce: None. I.M. Hernandez-Riveros: None. J. Vasquez-Vasquez: None. F.D. Martínez-Sánchez: None. J.L. Hernandez-Castillo: None. A. Pretel Gutiérrez: None. T.G. Jaramillo-Salazar: None. M.E. Rodriguez García: None. E.K. Tenorio-Aguirre: None. Introduction: An adrenal incidentaloma is a tumor detected on imaging conducted for reasons other than suspected adrenal disease. Whether an incidentaloma should be addressed during pregnancy has not been discussed since this condition is very uncommon. The correct diagnosis and treatment of a functional adrenal tumor has significant implications for maternal-fetal morbidity and mortality. Case Presentation: A 25-year-old woman at 37 weeks of gestation presented to the obstetric emergency department with a headache accompanied by tinnitus and dizziness. Arterial blood pressure at admission was 180/120 mmHg, and biochemical urinary analysis showed proteinuria. A diagnosis of preeclampsia was made, and an emergency cesarean section was performed due to fetal bradycardia. A live single neonate was delivered with an Apgar score of 5/9 at 1 and 5 minutes respectively. During surgery, the patient's arterial blood pressure persisted at 190/110 mmHg despite treatment with 20 mg intravenous hydralazine. At her admission to the intensive care unit, an esmolol infusion was indicated, but the patient further presented tachypnea and tachycardia. A chest Angio tomography ruled out pulmonary thromboembolism, but imaging of the abdomen revealed a right adrenal mass of 6 cm with a heterogeneous enhancement in the arterial phase. Considering the clinical evolution and the findings in tomography, a pheochromocytoma was suspected. The antihypertensive treatment was switched from labetalol to prazosin, achieving control of blood pressure and clinical improvement. The patient was discharged after five days to continue the approach of an incidentaloma. Contrast-enhanced abdominal MRI reported a 9 cm right adrenal mass with a heterogeneous center and hypointense areas suggestive of necrosis. Plasma-free metanephrine was reported at 128 pg/mL (reference value &amp;lt;100 pg/mL) and normetanephrine at 3976 pg/mL (reference value &amp;lt;126 pg/mL). A right adrenalectomy was scheduled. Conclusion: In the workup of an incidentaloma, suggestive characteristics of malignancy in TC, and functional evaluation guided by the patient's clinical manifestations must be addressed concurrently. In this case, the presence of an adrenal incidentaloma larger than 4 cm with &amp;gt;10 HU in a pregnant woman diagnosed with preeclampsia who had an inadequate response to the standard treatment led to the consideration of a probable pheochromocytoma as a secondary cause of hypertension, which influenced the change of antihypertensive treatment to alpha-adrenergic blockade, followed by patient clinical improvement. Although the presence of a pheochromocytoma is much less common than preeclampsia as a cause of hypertension in pregnancy, a misdiagnosis can increase maternal morbidity and mortality by up to 15%. After adequate treatment of the obstetric emergency, the approach to incidentaloma in pregnancy is recommended. Presentation: 6/3/2024

7025 Acute Psychosis and the Diagnosis of Cushing’s Syndrome: Lessons Learned from a Patient with a Long History of Obesity

Abstract Disclosure: S. Modi: None. L. Belalcazar: None. Background: Although the association of hypercortisolism and psychosis is well established, acute psychosis remains a very rare manifestation of Cushing’s syndrome, especially in the absence of previous psychiatric history. We present lessons learned from a patient in whom the diagnosis of Cushing’s syndrome was missed until the onset of acute psychosis helped identify his underlying endocrine disorder. Clinical Case: A 31-year-old male presented to the Emergency Department after being found down on the street. The patient had superficial lacerations that were suspected to be self-inflicted due to a suicide attempt, but later found to be the result of auditory hallucinations. He had no previous psychiatric history and no history of suicidal ideation. His medical history was positive for obesity since adolescence and a recent diagnosis of hypertension. His family noted that for the past several months he had been experiencing headache, fatigue, muscle weakness and, more recently, insomnia, restlessness, and confusion. Weight gain was noted, but of unknown magnitude. On admission, he was agitated and hallucinating. He was initially sedated with dexmedetomidine and started on quetiapine. Physical examination revealed Cushingoid features with truncal obesity (body mass index of 35 kg/m2), facial plethora, and dorsocervical fat pad; no abdominal striae were present. Labs showed mild hypokalemia. His AM cortisol was markedly elevated at &amp;gt; 123 ug/dL (normal 4.5-23.0 ug/dL) with an ACTH level at 144 pg/mL (normal 7.2-63.3 pg/mL). MRI Brain showed a 1.9 cm pituitary macroadenoma with small suprasellar extension. With a diagnosis of Cushing’s disease, later confirmed by pathology, he underwent transsphenoidal resection. AM cortisol on post-operative day 3 was 3.2 ug/dL (normal 4.5-23.0 ug/dL). Maintenance-dose steroids were started due to evidence of post-surgical corticotroph suppression. Notably, there was marked improvement in his anxiety, paranoia, and confusion post-operatively. Quetiapine and blood pressure medications were discontinued after discharge. Conclusion: In this patient, the diagnosis of Cushing’s syndrome was missed when initially presenting with new onset hypertension in the setting of long-standing obesity. Despite months of symptoms compatible with the diagnosis, it was not until he developed acute psychosis and a careful history was obtained, that the diagnosis of Cushing’s syndrome was entertained. Psychosis is present in only 3-8% of reported cases of Cushing’s syndrome. This case illustrates the importance of including Cushing’s syndrome in the differential diagnosis of acute psychosis, especially in patients without previous psychiatric history. It also highlights the need of excluding secondary causes of hypertension in young adults, with particular attention to Cushing’s syndrome in those who present with obesity, even if long-standing. Presentation: 6/1/2024

8437 Improved Quality Of Life&amp;Blood Pressure Following Diagnosis And Medical Management Of Primary Aldosteronism (PA) / Georgian Experience

Abstract Disclosure: Q. Gvazava: None. N. Zavrashvili: None. N. Shonia: None. Improved Quality of Life and Blood Pressure Following Diagnosis and Medical Management of Primary Aldosteronism (PA) - Georgian Experience Introduction: PA is the most common cause of secondary hypertension which still remains as an underdiagnosed condition in many countries, including Georgia. The choice of pharmacological or surgical therapy depends on the results of computed tomography scans of the adrenal glands and adrenal venous sampling. In patients with bilateral aldosterone hypersecretion, the optimal is a low-sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to reach a high-normal serum potassium concentration. Discussion: 60 y/o male with a 17-year history of hypertension. He was treated with 3 drug-program: valsartan, amlodipine, bisoprolol. BP was not adequately managed with systolic BP &amp;gt;140 mm/Hg. Patient had a history of hypokalaemia and required regular potassium supplements. Patient had never been evaluated for possible PA. We planned case detection test, which came up positive, with increased aldosterone, suppressed renin concentration and increased aldosterone-renin ratio. Abdominal CT performed 1 year ago for another reason revealed “normal” adrenals.After discussing treatment options patient preferred medical management and Eplerenone was started, dose titrated accordingly, K supplements were discontinued which over time resulted in decrease in requirement of his other antihypertensive medications, with BP adequately managed. Patient’s quality of life improved significantly, he has shared his test results and progress on his follow up visits; He is very grateful and feels content with the treatment. We present another case of 49 y/o male patient with a 19 year history of hypertension. Patient was treated with 4 drug-regimen: Valsartan, Hydrochlorothiazide, Amlodipine, nebivolol with average BP findings – 140/90 mm/Hg.Case detection test was positive with increased aldosterone, suppressed renin and increased aldosterone-renin ratio. Patient required confirmatory testing. Salt loading was done which confirmed the diagnosis of PA. On unenhanced CT of the abdomen, bilateral adrenal hyperplasia was found. Patient was started on Eplerenone, on follow up, his BP findings are significantly improved, number of BP meds are also decreased. Conclusion: Diagnosis of PA provides clinicians with unique opportunity to cure or effectively improve hypertension and hypokalaemia, as well as to prevent potential target organ damage and complications. That’s why the importance of increased awareness and having high clinical suspicion cannot be understated. Presentation: 6/3/2024

A-067 Simultaneous Measurement of Aldosterone and Plasma Renin Activity in Human Serum Using Liquid Chromatography Coupled to Tandem Mass Spectrometry for Clinical Research

Abstract Background The combination of primary aldosteronism (PA) and alterations in plasma renin activity (PRA) is a leading cause of secondary hypertension. An accurate measurement of Renin Angiotensin-Aldosterone System (RAAS) pathway improves the recognition of symptoms related to stroke, coronary disease, heart failure and metabolic syndrome. Methods Previously, surrogate matrices have been used when demonstrating the analytical performance of LC-MS/MS clinical research methods for the measurement of aldosterone and angiotensin I. Here, we have developed an analytically sensitive and reliable analytical strategy for simultaneous measurement of Aldosterone and Angiotensin I in human matrices. In-house calibrators and quality control samples were prepared, containing varying ranges of both aldosterone (20-2000pg/mL; 55-5548pmol/L) and angiotensin 1 (0.6-240ng/mL; 0.46-185nmol/L). The samples were extracted using the Oasis™ MAX 96-well µElution plate and then separated through the ACQUITY™ UPLC™ I-Class FL System using a XBridge™ Premier Peptide BEH™ C18 Column, over a run time of 3 minutes. Samples were then injected to Xevo™ TQ Absolute Mass Spectrometer, using both positive and negative acquisition modes. The downstream LC-MS/MS data analysis was performed using MassLynx™ MS Software. The analytical performance was demonstrated by extracting and quantifying two replicates of samples on two occasions per day over five separate days. Additionally, the stability of aldosterone and angiotensin I over the period of incubation (3-5hr) was evaluated, which is necessary when investigating the plasma renin activity in human Serum/Plasma samples. Results High reproducibility and repeatability were both determined, indicating total precision and repeatability (&amp;lt;15%CV) for both analytes and no significant changes were found in Aldosterone and Angiotensin I concentrations over 3-5hr of incubation. No significant system carryover (&amp;lt;10% of the lowest calibrator) from high concentration samples into subsequent blank injections was observed. In addition, calibration lines in human serum/plasma were linear, with coefficient of determinations (r2) &amp;gt;0.992 for all analyses at different incubation times. The analytical sensitivity of the clinical research method allows for precise quantification at 55 pmol/L for aldosterone and 0.46 nmol/L/hr for angiotensin I, with both analytes providing S/N (PtP) ≥10:1 and %RSD of &amp;lt;15% at these concentrations. Conclusions An analytically sensitive and selective clinical research method has been developed for the analysis of aldosterone and angiotensin I, using the Xevo TQ Absolute Mass Spectrometer. The Xevo TQ Absolute Mass Spectrometer enables the simultaneous analysis of physiologically low levels of aldosterone and plasma renin activity in human samples, (20pg/mL; 55pmol/L), (0.6ng/mL; 0.46nmol/h/L). A single test that improves instrument utilization, reduces cost, and allows the user to expand their existing test menu on the same platform has been established.

Executive summary of the Spanish consensus for the diagnosis, management, and follow-up of primary hyperaldosteronism.

Primary hyperaldosteronism (PH) is the most common cause of secondary hypertension (HTN) and is associated with a higher cardiometabolic risk than essential HTN. Nevertheless, PH remains clearly underdiagnosed. An early diagnosis and adequate treatment of this disease are essential to reduce the cardiometabolic morbimortality associated with aldosterone excess. PH follow-up is equally essential; however, there is little consensus on how it should be performed, being a topic rarely mentioned by the different clinical practice guidelines. The aim of this executive summary is to summarize the recommendations made in the Spanish consensus of PH for the diagnosis, management, and follow-up of these patients. The Spanish consensus was reached from a multidisciplinary perspective through a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), the Spanish Society of Cardiology (SEC), the Spanish Society of Nephrology (SEN), the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Radiology (SERAM), the Spanish Society of Vascular and Interventional Radiology (SERVEI), the Spanish Society of Laboratory Medicine (SEQC(ML)), the Spanish Society of Anatomic-Pathology (EAP), and the Spanish Association of Surgeons (AEC).

Prevalence and Risk Factors for Secondary Hypertension in Young Adults.

The prevalence of secondary causes of hypertension in young adults is unknown, and therefore, there is no consensus about the indication of screening of secondary hypertension (2HTN) in this population. The objective was to report the prevalence and the causes of 2HTN in young subjects. 2090 patients with confirmed hypertension aged 18 to 40 years with full workup for 2HTN screening were included in this cross-sectional study. We assessed the prevalence of 2HTN and analyzed the factors associated. 619/2090 patients (29.6%) had a 2HTN. The most frequent diagnoses of 2HTN in descending order were primary aldosteronism (n=339; 54.8%), renovascular hypertension (n=114; 18.4%), primary kidney disease (n=80; 12.9%), pheochromocytoma/functional paraganglioma (n=37; 5.9%), hypertension caused by drugs or substances (n=32; 6.0%), and other diagnoses (n=17; 2.7%). Patients with blood pressure <160/100 mm Hg did not have a lower prevalence of 2HTN regardless of the number of treatments. The prevalence of 2HTN was higher in the decade between 30 and 40 years of age than between 18 and 30 years of age (P=0.024). Female sex, hypokalemia, treatment with at least 2 medications, no familial history of hypertension, body mass index <25 kg/m², and diabetes were associated with a higher prevalence of 2HTN. The prevalence of 2HTN is high among young patients with hypertension (29.6% in our cohort), regardless of age and blood pressure level. All patients with hypertension under 40 years of age should be screened for secondary causes.