Diagnostic Approach Research Articles

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Case Report: Fetomaternal hemorrhage and its association with pronounced neonatal anemia

Fetomaternal hemorrhage (FMH) is a perplexing obstetric condition that predominantly occurs during the third trimester or at the time of delivery. Its insidious and non-specific onset often leads to diagnostic challenges. The underlying pathophysiology of FMH remains incompletely understood, though it is primarily attributed to compromise of the placental barrier. The severity of the condition is intrinsically associated with the volumn of blood loss, the hemorrhage rate, and the presence of alloimmunity. Upon the occurrence of severe FMH, it can rapidly lead to intrauterine distress, fetal anemia, and the possibility of fetal demise, presenting a considerable threat to both maternal and neonatal well-being. In this article, I present a substantial case of FMH and conduct a systematic review of the current scientific literature regarding the etiology, clinical manifestations, diagnostic approaches, treatment highlights, and prognosis of this condition. The objective of this work is to improve clinicians’ comprehension and diagnostic proficiency concerning FMH.

Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort.

The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.

Opportunities and challenges in the development of artificial intelligence research in spinal surgery

Artificial intelligence has emerged as a game-changer in the field of spine surgery, offering transformative diagnostic and therapeutic approaches for spinal conditions. The application of AI in spine research encompasses a diverse range of diseases, with usage scenarios becoming increasingly widespread and technological integration going deeper. AI technology shows immense promise and value in the diagnosis of spinal diseases, the formulation of treatment strategies, surgical navigation, prognostic evaluation, and postoperative rehabilitation. Through deep learning and machine learning, AI can aid doctors in enhancing diagnostic accuracy, creating personalized treatment plans, and executing precise maneuvers during surgery, thus improving operational safety. Moreover, AI can provide intelligent support for patients' postoperative recovery, facilitating the restoration of their functions. However, current research is still in its nascent stage and confronts several challenges, such as the lack of standardized databases, the simplicity of algorithmic learning models, the inadequate fusion of multi-modal clinical information, and the limited clinical applicability. By developing open-source, standardized spine databases, incorporating innovative intelligent core algorithms, and establishing normalized screening, diagnostic, and predictive models for spinal conditions, we trust that we can drive the innovation and refinement of diagnostic and treatment technologies in spine surgery. This will realize an effective conjunction between technological provision and clinical demands, continuously elevating the intelligence level of spine surgery and offering safer, more effective medical services to a vast array of patients.

Diagnostic and therapeutic approaches to a case of pregnancy complicated by bilateral adrenocortical adenomas with primary aldosteronism and Cushing's syndrome.

Aldosterone/cortisol co-secreting adenomas (A/CPA) are a rare type of primary aldosteronism(PA), and cases of aldosterone/cortisol co-secreting adenomas during pregnancy are extremely rare, with no reported cases to date. The unique physiological state of pregnancy increases cortisol secretion through the hypothalamic-pituitary-adrenal (HPA) axis and leads to elevated levels of all components of the renin-angiotensin-aldosterone system (RAAS). This can cause overlapping symptoms with abnormal cortisol and aldosterone secretion, making diagnosis very challenging. This case involves a 29-year-old woman who developed hypercortisolism at 33 weeks of pregnancy. Despite receiving treatment for her symptoms and having a successful delivery, she continued to experience hypertension and hypokalaemia after giving birth. Eventually, she was diagnosed with ACTH-independent Cushing's syndrome and primary aldosteronism due to independent cortisol and aldosterone secretion from bilateral adrenal adenomas. Following a thorough diagnosis, classification, treatment, and follow-up, the patient achieved a clinical cure while preserving normal adrenal function. Further investigation revealed that both diseases were caused by KCNJ5 and PRKACA mutations found in the bilateral adrenal adenomas.

Treatment of Late-onset Acute Graft-versus-host Disease Following Double Lung Transplantation Using a JAK2 Inhibitor.

Acute graft-versus-host disease (aGVHD) is a rare but potentially life-threatening complication that can occur after solid organ transplantation, particularly in organs with abundant lymphoid tissue like the liver and intestines. While less common in lung transplants, the rising numbers of these procedures have brought more attention to aGVHD, usually appearing within the first 3-mo posttransplant. Given its relative rarity, a clear understanding of the pathophysiology, risk factors, diagnostic, and management strategies remain elusive. These knowledge gaps can lead to delays in diagnosis and the initiation of appropriate treatment leading to predictably inferior outcomes. Managing aGVHD following solid organ transplantation is challenging, and there is no standard approach. Current management involves high-dose steroids and other immunosuppressive drugs. However, these interventions are associated with serious complications, including potentially fatal infections, underscoring the urgent need for more research to refine both diagnostic methods and treatment approaches and ultimately improving patient outcomes. In this report, we aim to deepen our understanding of aGVHD following lung transplants and share our experience with a unique case of aGVHD occurring almost a year after lung transplantation that was successfully managed using ruxolitinib, describing a potential treatment approach modeled on the contemporary management of stem cell transplant associated aGVHD.

Association of ANRIL Gene Polymorphisms with Gastric Cancer Risk: A Case-Control Study.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

Profiling the skill mastery of introductory programming students: A cognitive diagnostic modeling approach

Profiling the skill mastery of introductory programming students: A cognitive diagnostic modeling approach

Valence-engineered catalysis-selectivity regulation of molybdenum oxide nanozyme for acute kidney injury therapy and post-cure assessment.

The optimization of the enzyme-like catalytic selectivity of nanozymes for specific reactive oxygen species (ROS)-related applications is significant, and meanwhile the real-time monitoring of ROS is really crucial for tracking the therapeutic process. Herein, we present a mild oxidation valence-engineering strategy to modulate the valence states of Mo in Pluronic F127-coated MoO3-x nanozymes (denoted as MF-x, x: oxidation time) in a controlled manner aiming to improve their specificity of H2O2-associated catalytic reactions for specific therapy and monitoring of ROS-related diseases. Experimentally, MF-0 (Mo average valence 4.64) and MF-10 (Mo average valence 5.68) exhibit exclusively optimal catalase (CAT)- or peroxidase (POD)-like activity, respectively. Density functional theory (DFT) calculations verify the most favorable reaction path for both MF-0- and MF-10-catalyzed reaction processes based on free energy diagram and electronic structure analysis, disclosing the mechanism of the H2O2 activation pathway on the Mo-based nanozymes. Furthermore, MF-0 poses a strong potential in acute kidney injury (AKI) treatment, achieving excellent therapeutic outcomes in vitro and in vivo. Notably, the ROS-responsive photoacoustic imaging (PAI) signal of MF-0 during treatment guarantees real-time monitoring of the therapeutic effect and post-cure assessment in vivo, providing a highly desirable non-invasive diagnostic approach for ROS-related diseases.

On the possibility of studying the effect of magnetic reconnection in a laboratory astrophysical experiment using X-ray emission L-spectra of multiply charged ions

The paper considers the application of X-ray spectroscopy with high spatial resolution for investigation of magnetic reconnection in laboratory astrophysical experiments carried out on laser facilities of nano- and pico-second duration at moderate laser intensity on the target 1018 W/cm2. A brief overview of commonly used experimental schemes is given. We present atomic kinetic calculations for the spectra from the L-shells of Ne- and F-like iron ions (Fe, Z = 26), which demonstrate the high sensitivity of the spectra to changes in plasma parameters. An analysis of the range of applicability of various diagnostic approaches to assessing the electron temperature and laser plasma density is carried out. It is shown that transition lines in Ne-like ions are a universal tool for measuring plasma parameters, both in the region of laser interaction with the target and in the reconnection zone.

Core CSF Biomarker Profile in Cerebral Amyloid Angiopathy: Updated Meta-Analysis.

There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort to improve diagnostics, especially in the context of patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA is the driver of amyloid-related imaging abnormalities). We performed an updated meta-analysis of 5 core CSF biomarkers (Aβ42, Aβ40, Aβ438, total tau [T-tau], and phosphorylated tau [P-tau]) to assess which of these are most altered in sporadic CAA. We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting APP metabolism (Aβ42, Aβ40, Aβ38), neurodegeneration (T-tau), and tangle pathology (P-tau), in symptomatic sporadic CAA cohorts (based on the Boston criteria) vs control groups and/or vs patients with AD. Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations in (1) patients with CAA to controls and (2) CAA to patients with AD. RoM >1 indicates higher biomarker concentration in CAA vs comparison population, and RoM <1 indicates higher concentration in comparison groups. 8 studies met inclusion criteria: a total of 11 CAA cohorts (n = 289), 9 control cohorts (n = 310), and 8 AD cohorts (n = 339). Overall included studies were of medium quality based on our assessment tools. CAA to controls had lower mean level of all amyloid markers with CSF Aβ42, Aβ40, and Aβ38 RoMs of 0.46 (95% CI 0.38-0.55, p < 0.0001), 0.70 (95% CI 0.63-0.78, p < 0.0001), and 0.71 (95% CI 0.56-0.89, p = 0.003), respectively. CSF T-tau and P-tau RoMs of patients with CAA to controls were both greater than 1: 1.56 (95% CI 1.32-1.84, p < 0.0001) and 1.31 (95% CI 1.13-1.51, p < 0.0001), respectively. Differentiation between CAA and AD was strong for CSF Aβ40 (RoM 0.76, 95% CI 0.69-0.83, p < 0.0001) and Aβ38 (RoM 0.55, 95% CI 0.38-0.81, p < 0.0001), but not Aβ42 (RoM 1.00; 95% CI 0.81-1.23, p = 0.970). For T-tau and P-tau, average CSF ratios in patients with CAA vs AD were 0.64 (95% CI 0.58-0.71, p < 0.0001) and 0.64 (95% CI 0.58-0.71, p < 0.0001), respectively. Specific CSF patterns of Aβ42, Aβ40, Aβ38, T-tau, and P-tau might serve as molecular biomarkers of CAA, in research and clinical settings, offering the potential to improve the clinical diagnostic approach pathway in specific scenarios.

Non-Invasive Diagnostic Approaches for Kidney Disease: The Role of Electronic Nose Systems

Kidney diseases are a group of conditions related to the functioning of kidneys, which are in turn unable to properly filter waste and excessive fluids from the blood, resulting in the presence of dangerous levels of electrolytes, fluids, and waste substances in the human body, possibly leading to significant health effects. At the same time, the toxins amassing in the organism can lead to significant changes in breath composition, resulting in halitosis with peculiar features like the popular ammonia breath. Starting from this evidence, scientists have started to work on systems that can detect the presence of kidney diseases using a minimally invasive approach, minimizing the burden to the individuals, albeit providing clinicians with useful information about the disease’s presence or its main related features. The electronic nose (e-nose) is one of such tools, and its applications in this specific domain represent the core of the present review, performed on articles published in the last 20 years on humans to stay updated with the latest technological advancements, and conducted under the PRISMA guidelines. This review focuses not only on the chemical and physical principles of detection of such compounds (mainly ammonia), but also on the most popular data processing approaches adopted by the research community (mainly those relying on Machine Learning), to draw exhaustive conclusions about the state of the art and to figure out possible cues for future developments in the field.

An integrated method for detecting lung cancer via CT scanning via optimization, deep learning, and IoT data transmission

With its increasing global prevalence, lung cancer remains a critical health concern. Despite the advancement of screening programs, patient selection and risk stratification pose significant challenges. This study addresses the pressing need for early detection through a novel diagnostic approach that leverages innovative image processing techniques. The urgency of early lung cancer detection is emphasized by its alarming growth worldwide. While computed tomography (CT) surpasses traditional X-ray methods, a comprehensive diagnosis requires a combination of imaging techniques. This research introduces an advanced diagnostic tool implemented through image processing methodologies. The methodology commences with histogram equalization, a crucial step in artifact removal from CT images sourced from a medical database. Accurate lung CT image segmentation, which is vital for cancer diagnosis, follows. The Otsu thresholding method and optimization, employing Colliding Bodies Optimization (CBO), enhance the precision of the segmentation process. A local binary pattern (LBP) is deployed for feature extraction, enabling the identification of nodule sizes and precise locations. The resulting image underwent classification using the densely connected CNN (DenseNet) deep learning algorithm, which effectively distinguished between benign and malignant tumors. The proposed CBO+DenseNet CNN exhibits remarkable performance improvements over traditional methods. Notable enhancements in accuracy (98.17%), specificity (97.32%), precision (97.46%), and recall (97.89%) are observed, as evidenced by the results from the fractional randomized voting model (FRVM). These findings highlight the potential of the proposed model as an advanced diagnostic tool. Its improved metrics promise heightened accuracy in tumor classification and localization. The proposed model uniquely combines Colliding Bodies Optimization (CBO) with DenseNet CNN, enhancing segmentation and classification accuracy for lung cancer detection, setting it apart from traditional methods with superior performance metrics.

Clinically oriented look into diagnostics and therapy of primary sclerosing cholangitis. Review of literature

Introduction: Primary sclerosing cholangitis (PSC) is a complex liver disorder marked by multifocal bile duct strictures and dilatations, leading to cholestasis and liver fibrosis. Although the exact cause is unknown, autoimmune mechanisms are strongly suspected. Aim of the Study: This paper reviews current knowledge on PSC, covering its etiology, prevalence, treatment options, and practical management strategies. Current State of Knowledge: PSC management focuses on symptom relief and liver transplantation, with limited success in pharmacological treatments. New therapies, including immune modulators and anti-fibrotic agents, show promise but require further research. Liver transplantation remains the most effective treatment, though recurrence risks necessitate ongoing monitoring. Materials and Methods: This article reviews the current understanding of PSC, including its pathophysiology, diagnostic approaches, clinical features, and management strategies. A comprehensive literature search was conducted using PubMed and Google Scholar, with articles selected based on relevant keywords and evaluated for inclusion in this review. Conclusions: Effective management of PSC necessitates a multidisciplinary approach involving hepatologists, gastroenterologists, radiologists, and transplant surgeons. Ongoing efforts to better understand PSC’s pathogenesis, refine diagnostic methods, and develop more effective therapies are crucial for improving patient outcomes.

Diagnostic and Therapeutic Approach to a Neuroenteric Cyst in the Lumbar Spine

Diagnostic and Therapeutic Approach to a Neuroenteric Cyst in the Lumbar Spine

A new algorithm for coeliac disease based on the 'long forgotten' TCRγδ+ intra-epithelial lymphocytes detected with an antibody working on FFPE sections.

Diagnosis of coeliac disease (CD) with mild mucosal changes is difficult for all parties involved. We aimed to determine the power of Tcell receptor (TCR)γδ+ intra-epithelial lymphocytes (IELs) in discriminating CD from other causes of intra-epithelial lymphocytosis using a new monoclonal antibody. A total of 167 cases categorised as coeliac (117 untreated CD, classified according to Marsh, updated by Ensari, including 29 type 1, 29 type 2, 39 type 3 and 20 treated CD), and non-coeliac groups (24 controls and 26 non-coeliac IELosis) based on clinical, serological and histological data were studied for IEL counts enumerated per 100 enterocytes using haematoxylin and eosin, CD3, TCR δ-stains. TCRγδ+ IELs were significantly higher in CD (24.83 ± 16.13) compared to non-CD (6.72 ± 6.32) and were correlated with the degree of mucosal damage. Both γδ+ IEL count and ratio showed higher performance in differentiating untreated coeliacs from controls, with a sensitivity of 83.76; 85.57 and specificity of 95.83; 79.17, respectively. TCRγδ+ IEL counts distinguished type 1 CD (20.41 ± 13.57) from non-coeliac IELosis (9.42 ± 7.28) (p = 0.025). Discriminant analysis revealed that villus/crypt ratio, γδ+ and CD3+ IEL counts, γδ+/CD3+IEL ratio, IEL distribution pattern were potent discriminants and correctly classified 82.3% of cases while the algorithm accurately diagnosed 93.4% of cases. The new antibody detecting γδ+ IELs in FFPE sections revealed thresholds of 10.5 for γδ+ IELs and 14% for γδ+/CD3+IEL ratio which distinguished coeliacs from non-coeliacs with high sensitivity and specificity, particularly in cases with normal villus/crypt axis including type 1 CD, non-CD IELosis and controls. A 'coeliac algorithm' based on γδ+ IELs is proposed with the hope that it will be used in the histopathological diagnostic approach by the pathology community.

Diagnostic Approach to Children with Unexplained Global Developmental Delay in Pediatric Neurology Outpatient Clinic.

Global developmental delay (GDD) is a common pediatric disorder that affects up to 3% of children. Due to the heterogeneous etiology of GDD, diagnostic procedures and algorithms are complex and diverse. The aim of our study was to investigate the diagnostic yield of genetic, metabolic, and imaging studies in establishing the etiology of unexplained GDD (UGDD). In this retrospectively observational study, we examined the medical records of all children diagnosed with UGDD at the Department of Pediatric Neurology, University Medical Centre Ljubljana, Slovenia between January and December 2019. We evaluated the effectiveness of various genetic, metabolic, and magnetic resonance imaging (MRI) tests in identifying the underlying cause of GDD. Additionally, we assessed subgroups of patients to determine whether any of the studied tests were particularly beneficial based on their clinical symptoms. A total of 123 patients met the inclusion criteria, with a median age of 4.3 years (range, 0 - 16 years), of which 71 (57.7%) were males. Genetic diagnosis was established in 47.1% (58/123) of patients. Metabolic laboratory testing did not identify a metabolic disease in any of the tested participants (114/123) and MRI was critical for diagnosis in only 1/81 (1.2%) patient. Our findings strongly suggest that genetic testing surpasses MRI and metabolic testing in establishing the etiology of unexplained global developmental delay in a pediatric neurology outpatient setting. This information will help guide the diagnostic evaluation of these children.

Development of a Digital Twin Driven by a Deep Learning Model for Fault Diagnosis of Electro-Hydrostatic Actuators

The first quarter of the 21st century has witnessed many technological innovations in various sectors. Likewise, the COVID-19 pandemic triggered the acceleration of digital transformation in organizations driven by artificial intelligence and communication technologies in Industry 4.0 and Industry 5.0. Aiming at the construction of digital twins, virtual representations of a physical system allow real-time bidirectional communication. This will allow the monitoring of operations, identification of possible failures, and decision making based on technical evidence. In this study, a fault diagnosis solution is proposed, based on the construction of a digital twin, for a cloud-based Industrial Internet of Things (IIoT) system contemplating the control of electro-hydrostatic actuators (EHAs). The system was supported by a deep learning model using Long Short-Term Memory (LSTM) networks for an effective diagnostic approach. The implemented study considers data preparation and integration and system development and application to evaluate the performance against the fault diagnosis problem. According to the results obtained, positive results are shown in the construction of the digital twin using a deep learning model for the fault diagnosis problem of an active EHA-IIoT configuration.

Renewable Energy in Sub-Saharan Africa: A Prescriptive Analysis of Ghana

This study assesses the state of play of renewable energy in Sub-Saharan Africa through the lens of the Ghana renewable energy sub-sector. Adopting a sector diagnostic approach, the study assesses the legal framework, institutional arrangements, emerging developments, and challenges of renewable energy development in Ghana. The study further prescribes key renewable policy instruments necessary to propel Ghana to achieve its 10% renewable energy target by 2030. Recommended amendments for the Renewable Energy Act are also proffered in this paper. The study provides innovative directions for policymakers and regulators while revealing new perspectives to the renewable energy puzzle in Africa.

7764 A Case of Primary Hyperaldosteronism With Negative Imaging Findings -Diagnostic Approach and Outcome in a Decade

Abstract Disclosure: U.D. Gupta: None. M. Al-Ghuraibawi: None. R. Abdulhussein: None. K. Panigrahi: None. Z. Deribe: None. Distinguishing between the various subtypes of primary hyperaldosteronism (PHA) poses a clinical challenge. Nevertheless, it is notable that primary hyperaldosteronism is a prominent contributor to secondary hypertension, accounting for less than 1% of cases. The triad of hypertension, hypokalemia, and metabolic alkalosis demands screening for PHA. While bilateral adrenal hyperplasia and aldosterone-producing adenomas (APA) are common, rarer forms like unilateral adrenal hyperplasia and glucocorticoid-responsive aldosteronism can also occur. In our case, a 61-year-old patient has been diagnosed and treated for primary hyperaldosteronism for last 10-years. Presently, the patient is undergoing management for blood pressure with a medication regimen comprising Amiloride, Nifedipine, Minoxidil, Atenolol, and Eplerenone over the past decade. No abnormal findings were observed in the computed tomography or magnetic resonance imaging of the adrenal gland, and adrenal venous sampling test results were non-conclusive. The patient has exhibited favorable outcomes with medications, also subsequent imaging has not revealed the presence of an adrenal mass. This case is presented as unique due to its atypical presentation, characterized by the absence of anatomical lesions in the adrenal gland and non-conclusive sampling test results. Nevertheless, the patient responded positively to treatment, supported by the diagnostic significance of preliminary lab tests for primary hyperaldosteronism (aldosterone level: 20.5; plasma renin activity: 0.19, initially aldosterone levels were 17 and 7 before and after saline infusion). Notably, literature acknowledges that the aldosterone-producing adenomas (APAs) can be very small, sometimes &amp;lt;3 mm in diameter, and lesions &amp;lt;1 cm may be overlooked on CT scans. The limitation of adrenal venous sampling (AVS) is the challenge in obtaining good sample due to technical difficulties and variations in local expertise, success rates in AVS may vary. This case exemplifies the diagnostic complexities encountered in primary hyperaldosteronism cases, where imaging and adrenal venous sampling, though frequently recommended, may pose challenges. In conclusion, we share insights from this case and its treatment outcome. Clinically, a thorough assessment of symptoms, along with laboratory results, is crucial for diagnosis and treatment and further categorization may be challenging without imaging and adrenal venous sampling. Presentation: 6/3/2024