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Aging is a complex process associated with multimorbidity. Hypertension, one of widespread states, is among main causes of age-related alterations in behavior, emotionality and sociability. We studied the effects of long-term isolated housing on anxiety, depressive-like and social behavior as well as changes in the adrenocortical and sympathetic systems in the aging normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Ten-month-old male rats of both strains were subjected to 90-day isolated or group housing. Surprisingly, social isolation induced only mild effect on anxiety without influencing other affective-related behaviors. No effects of isolated housing on sociability or social novelty preferences were revealed. Despite the adrenal gland hypertrophy in the SHRs, corticosterone levels remained stable within the period of isolation but the expression of nuclear glucocorticoid receptor (Nr3c1) mRNA in the adrenals was lower in the SHR as compared to WKY rats. Pre-existing hypertension, associated with SHR genotype, did not significantly contribute to the effects of social isolation. The data suggest that the aged WKY and SHR rats are relatively resilient to chronic social stress associated with isolated housing. [ABSTRACT FROM AUTHOR]

Background Patients and Methods Results Conclusion Partial adrenalectomy (PA), as an alternative to total adrenalectomy in selected cases, allows for the preservation of adrenocortical function, especially in hereditary and/or bilateral diseases. In this study, we analyze our experience in posterior retroperitoneoscopic PA (PRPA) and its impact on adrenocortical function.From January 2010 to December 2023, 709 PRPAs were performed on 766 adrenal glands in a total of 697 patients (421F; 276M; and mean age 49.3 ± 15.3). Patients suffered from all types of adrenal tumors (239 pheochromocytoma, 225 Conn's syndrome, 102 Cushing's syndrome (CS), 66 nonfunctioning adenomas, 38 adrenal metastases, and 27 others). Mean tumor size was 2.7 ± 1.5 cm. Bilateral disease occurred in 135 patients (60 pheochromocytoma, 19 Conn's syndrome, 32 CS, 2 nonfunctioning adenomas, 17 adrenal metastases, and 5 combined diseases).Mean operating time for unilateral operation was 39.2 ± 17.2 min. Minor postoperative complications were observed in 1.5% and major complications in 0.1%. The median hospital stay was 2 days. In bilateral cases, 18 of 33 (54%) Cushing patients and nine of 102 (9%) non‐Cushing patients received corticosteroid replacement therapy (CRT) early postoperatively. Long‐term follow‐up data were collected for 242 patients (35%). After unilateral surgery, only patients with CS required CRT (8/24). Eleven (24.4%) out of 45 patients with bilateral non‐Cushing disease needed CRT. Eight patients (3%) developed ipsilateral recurrent disease.PRPA is a safe procedure with a low complication and recurrence rate. This makes it the preferred operation in cases of bilateral disease and for selected patients with benign pathologies. [ABSTRACT FROM AUTHOR]

• Human GH transgenic rats exhibit hyperphagia and obesity from a young age. • TG rats showed hypercorticosteronemia accompanying enlarged adrenal glands. • ADX blunted, and glucocorticoids supplement alleviated hyperphagia only in TG rats. • Group housing prevented hyperphagia and hypercorticosteronemia in TG rats. Hyperphagia and subsequent obesity are important public health issues due to the associated risks of developing serious diseases. Certain stressors play a major role in the development of hyperphagia. In previous studies, we established a line of human growth hormone transgenic (TG) rats that exhibit hyperphagia and obesity from a young age. We recently demonstrated that voluntary running on a running wheel alleviates hyperphagia in TG rats. Wheel running provides environmental enrichment for rodents and plays a role in relieving stress. These results suggested that stress is the major factor inducing hyperphagia in TG rats. Thus, in the present study, we evaluated activation of the hypothalamus–pituitary–adrenal axis. TG rats showed bilateral enlargement of adrenal glands and hypercorticosteronemia, although their hypothalamic CRH level was comparable to that of wild-type (WT) rats. The ACTH-immunoreactive area was larger and the serum ACTH level in the dark phase was higher in TG rats than in WT rats. Adrenalectomy reduced the food intake of TG rats to a level comparable to that in WT rats, and supplying glucocorticoids recurred hyperphagia in TG rats. These treatments did not affect the food intake of WT rats. Rearing TG rats under group housing prevented hyperphagia and hypercorticosteronemia. These results suggest that glucocorticoids are appetite stimulants, and that TG rats exhibit increased sensitivity to the appetite-stimulating effect of glucocorticoids. [ABSTRACT FROM AUTHOR]

Introduction: Retroperitoneal bronchogenic cyst, typically situated in the subdiaphragmatic region, is a rare congenital benign developmental abnormality arising from dysplasia of the foregut and abnormal budding of the tracheobronchial tree. Due to its low incidence, there are limited reports regarding this condition. Case presentation: Four retroperitoneal bronchogenic cysts near the left adrenal gland were identified without accompanying clinical symptoms. One case was misdiagnosed as an adrenal tumor prior to surgery, while the others were diagnosed as retroperitoneal cysts of uncertain origin. All cases underwent surgical resection, with three being performed laparoscopically and one utilizing robot-assisted techniques. Pathological reports confirmed the diagnosis of bronchogenic cyst in each instance. The prognosis was favorable for all four patients, with no complications or recurrences observed. Additionally, a literature review was conducted, encompassing 82 cases, which revealed similar characteristics and radiological manifestations in the majority of cases. Conclusion: Although retroperitoneal bronchogenic cysts are rare developmental malformations lacking distinctive clinical and radiological features, reported cases exhibit similarities in certain clinical and imaging characteristics. This report offers additional insights into the diagnosis and management of this rare disease. Future reports are essential to enhance understanding of this disease. [ABSTRACT FROM AUTHOR]

Percutaneous image-guided ablation techniques are a consolidated therapeutic alternative for patients with high preoperative surgical risk for the management of oncological diseases in multiple body districts. Each technique has both pros and cons according to the type of energy delivered, mechanism of action, and site of application. The present article reviews the most recent literature results on ablation techniques applied in the field of genitourinary diseases (kidney, adrenal glands, prostate, and uterus), describing the advantages of the use of each technique and their technical limitations and summarizing the major recommendations from an international consensus meeting. Critical relevant statement: The article critically evaluates the efficacy and safety of ablation therapies for various genitourinary tract diseases, demonstrating their potential to improve patient outcomes and advance clinical radiology by offering minimally invasive, effective alternatives to traditional surgical treatments. Key Points: Ablation therapies are effective alternatives to surgery for renal cell carcinoma. Ablation techniques offer effective treatment for intermediate-risk prostate cancer. Ablation is a promising tool for adrenal tumor management. Ablation reduces fibroid symptoms and volume, offering an alternative to surgery. [ABSTRACT FROM AUTHOR]

Hypertension is a multifactorial disease with stage-specific gene expression changes occurring in multiple organs over time. The temporal sequence and the extent of gene regulatory network changes occurring across organs during the development of hypertension remain unresolved. In this study, female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were used to analyze expression patterns of 96 genes spanning inflammatory, metabolic, sympathetic, fibrotic, and renin-angiotensin (RAS) pathways in five organs, at five time points from the onset to established hypertension. We analyzed this multi-dimensional dataset containing ~15,000 data points and developed a data-driven dynamic network model that accounts for gene regulatory influences within and across visceral organs and multiple brainstem autonomic control regions. We integrated the data from female SHR and WKY with published multiorgan gene expression data from male SHR and WKY. In female SHR, catecholaminergic processes in the adrenal gland showed the earliest gene expression changes prior to inflammation-related gene expression changes in the kidney and liver. Hypertension pathogenesis in male SHR instead manifested early as catecholaminergic gene expression changes in brainstem and kidney, followed by an upregulation of inflammation-related genes in liver. RAS-related gene expression from the kidney-liver-lung axis was downregulated and intra-adrenal RAS was upregulated in female SHR, whereas the opposite pattern of gene regulation was observed in male SHR. We identified disease-specific and sex-specific differences in regulatory interactions within and across organs. The inferred multi-organ network model suggests a diminished influence of central autonomic neural circuits over multi-organ gene expression changes in female SHR. Our results point to the gene regulatory influence of the adrenal gland on spleen in female SHR, as compared to brainstem influence on kidney in male SHR. Our integrated molecular profiling and network modeling identified a stage-specific, sex-dependent, multi-organ cascade of gene regulation during the development of hypertension. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy characterized by renal potassium loss, hypokalemia, metabolic alkalosis, hypocalciuria, hypomagnesemia, and hyper-reninemic hyperaldosteronism. Finerenone is a non-steroidal mineralocorticoid receptor antagonist that inhibits receptor-mediated sodium reabsorption and decreases receptor overactivation. This report describes a 35-year-old man with hypokalemia, a mass in the right adrenal gland, and a diagnosis of Gitelman syndrome with a c.1456>A heterozygous variant of the SLC12A3 gene, treated with finerenone. Case Report: A 35-year-old man was admitted to the affiliated Hospital of Qingdao University because of a mass in the right adrenal gland. He was in generally good condition upon admission. He was a non-smoker and non-drinker. The examination at admission led to diagnosis of severe hypokalemia. Genetic tests showed that he carried a homozygous pathogenic variant c.1456>A in SLC12A3, which can confirm the diagnosis of Gitelman syndrome. Spironolactone was used to increase the blood potassium level, but after adverse effects were noted, finerenone was used, which greatly improved his blood potassium levels. Conclusions: For patients with Gitelman syndrome who cannot tolerate adverse effects such as sex hormone-related adverse reactions from using non-selective mineralocorticoid receptor antagonists, especially male patients, finerenone may be considered as an adjunct therapy for potassium retention and magnesium supplementation. To the best of our knowledge, this is the first report in the world of using finerenone to treat Gitelman syndrome. This provides more options for treatment of patients in the future. [ABSTRACT FROM AUTHOR]

Background: The penis is a relatively uncommon organ for metastases. Secondary lesions often originate from the bladder, prostate, or rectosigmoid cancers. Only a few cases have described penile lesions secondary to lung cancers, mostly as a later complication. Case Description: We hereby report the case of an 86‐year‐old male patient who presented with a 3‐week‐long nonpainful priapism. A penile Doppler ultrasound and a chest and abdominal CT scan were performed, showing a left hilar lung mass as well as lesions in the liver, the adrenal glands, the pancreas, bone structures, and the penis. Penile metastasis is associated with a poor prognosis because of the frequent disseminated malignant lesions in other sites. Conclusion: Malignant priapism should be suspected, especially in patients with no evident risk factors for priapism (hematological diseases, drugs, alcohol, neurological diseases, or metabolic disorders). [ABSTRACT FROM AUTHOR]

This review describes the impact of COVID-19 on the endocrine system, focusing on cortisol signaling and growth factor-induced endocrine resistance. As expected, SARS-CoV-2 infection induces systemic inflammation, resulting in stimulation of the adrenal glands leading to elevated cortisol levels with normal adrenocorticotropic hormone (ACTH) levels. The cytokine storm could also stimulate cortisol production. However, in some instances, cortisol levels rise independently of ACTH due to a phenomenon known as "pseudo-Cushing's syndrome," where adrenal glands become less responsive to ACTH. Plasma proteomic analyses showed that this pattern was variably observed among COVID-19 patients, potentially involving calcium dysregulation and GNAS-regulated activities, ultimately impacting the regulation of microvascular permeability. COVID-19 also exhibited a syndrome resembling endocrine resistance, governed by receptor tyrosine kinase signaling pathways. Mild cases displayed elevated activity of EGFR and MMP9, along with increased expression of survival factors like Bax and Bcl2. In contrast, more severe cases involved IGFR-I and enhanced NOTCH signaling, with altered expression of Bcl2, AKT1, and MAPK8. In summary, these findings describe the complex interplay between COVID-19 and endocrine pathology, particularly endocrine resistance. These insights suggest potential endocrine targets for therapeutic interventions to improve short- and long-term outcomes for COVID-19 patients. [ABSTRACT FROM AUTHOR]

Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)‐independent and ACTH‐dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH‐independent hypercortisolemia. ACTH is derived from pro‐opiomelanocortin, and its processing involves prohormone convertase 1/3. High‐molecular‐weight ACTH is generally found in ACTH‐producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high‐molecular‐weight ACTH alternation during ACTH‐independent Cushing's syndrome remain unclear. A 40‐year‐old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH‐independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non‐suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high‐molecular‐weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high‐molecular‐weight ACTH levels was observed. Histological findings revealed cortisol‐producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high‐molecular‐weight ACTH. The observed decline in high‐molecular‐weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic–pituitary–adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH‐related molecules warrants further exploration to enhance our understanding of the hypothalamic–pituitary–adrenal axis feedback mechanism. [ABSTRACT FROM AUTHOR]

Adrenocortical disorders encompass a broad spectrum of conditions ranging from benign hyperplasia to malignant tumors, significantly disrupting hormone balance and causing a variety of clinical manifestations. By leveraging next-generation sequencing and in silico analyses, recent studies have uncovered the genetic and molecular pathways implicated in these transitions. In this review, we explored the molecular and genetic alterations in adrenocortical disorders, with a particular focus on the transitions from normal adrenal function to hyperfunction. The insights gained are intended to enhance diagnostic and therapeutic strategies, offering up-to-date knowledge for managing these complex conditions effectively. [ABSTRACT FROM AUTHOR]

Genome-Wide Association Studies (GWAS) have been decisive in elucidating the genetic predisposition of neuroblastoma (NB). The majority of genetic variants identified in GWAS are found in non-coding regions, suggesting that they can be causative of pathogenic dysregulations of gene expression. Nonetheless, pinpointing the potential causal genes within implicated genetic loci remains a major challenge. In this study, we integrated NB GWAS and expression Quantitative Trait Loci (eQTL) data from adrenal gland to identify candidate genes impacting NB susceptibility. We found that ZMYM1, CBL, GSKIP and WDR81 expression was dysregulated by NB predisposing variants. We further investigated the functional role of the identified genes through computational analysis of RNA sequencing (RNA-seq) data from single-cell and whole-tissue samples of NB, neural crest, and adrenal gland tissues, as well as through in vitro differentiation assays in NB cell cultures. Our results indicate that dysregulation of ZMYM1, CBL, GSKIP, WDR81 may lead to malignant transformation by affecting early and late stages of normal program of neuronal differentiation. Our findings enhance the understanding of how specific genes contribute to NB pathogenesis by highlighting their influence on neuronal differentiation and emphasizing the impact of genetic risk variants on the regulation of genes involved in critical biological processes. [ABSTRACT FROM AUTHOR]

Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. This study provides a comprehensive retrospective evaluation of 15 patients diagnosed with metastatic or recurrent PPGL at our institution over a two-decade span (2000–2020). Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. Median duration from initial PPGL diagnosis to the onset of metastasis or recurrence stood at 5.8 years. Predominant sites for metastasis included the bone, lung, lymph nodes, and peritoneum. A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. These insights not only underscore the clinical variability of PPGL's progression but also highlight the pivotal role of surgical management for metastatic or recurrent cases. The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. Given the intricacies of PPGL, collaborative studies involving larger patient cohorts will be crucial to optimize management strategies and prognostication. [ABSTRACT FROM AUTHOR]

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Triple A syndrome (TAS), also known as Allgrove syndrome (OMIM#231550), is a rare, autosomal recessive disorder characterized by the triad of alacrima, achalasia, and adrenal insufficiency. Additional neurological features may be present in two-thirds of patients, involving central, peripheral, and autonomic nervous system manifestations. TAS is caused by genetic alterations in the AAAS gene on chromosome 12q13, which encodes the nuclear pore complex protein termed ALADIN (ALacrima, Achalasia, aDrenal Insufficiency, and Neurologic disorder). ALADIN plays a crucial role in nucleocytoplasmic transport of specific proteins, including the transport of DNA repair proteins. TAS exhibits significant phenotypic variability in terms of symptom onset, frequency, and severity, often presenting with a progressive clinical course indicative of an underlying degenerative process. In this study, we report the case of an infant with exceptionally early and severe manifestations of triple A syndrome, with a review of the literature. Our patient exhibited the complete classical triad of TAS at six months of age, being among the youngest reported cases of the syndrome. The clinical course was complicated by severe involvement of the autonomic nervous system, neurogenic bladder, and recurrent urinary tract infections. Subsequently, the patient developed acute pancreatitis, leading to multiorgan dysfunction and a fatal outcome at 25 months of age. This case underscores the potential for atypical disease presentations and the need for clinical awareness in diagnosing and managing patients with TAS. [ABSTRACT FROM AUTHOR]

Background: Bilateral adrenal hemorrhage is a rare but often a fatal cause of primary adrenal insufficiency that can result in adrenal crisis if not identified and managed appropriately. Case presentation: We present a case of a 27-year-old Caucasian female who was admitted to the hospital 17 days postpartum with pleuritic chest and flank pain, shortness of breath and nausea. Computed tomography imaging confirmed multiple thromboemboli including pulmonary emboli and noted bilateral bulky adrenal glands. She was managed for infection and pulmonary emboli; however, she complained of persistent headaches, nausea, and vomiting despite appropriate management. Radiology re-review found the computed tomography imaging was consistent with bilateral adrenal hemorrhage in hindsight. Subsequent endocrine evaluation with hypothalamic–pituitary–adrenal axis interrogation and adrenocorticotropic hormone (Synacthen) stimulation testing confirmed resultant primary adrenal insufficiency. She required urgent intravenous hydrocortisone and was subsequently discharged on oral adrenal replacement therapy and anticoagulation. Conclusions: Delay in identification and treatment of adrenal insufficiency can lead to catastrophic outcomes. This case highlights the challenge of diagnosing bilateral adrenal hemorrhage and resultant adrenal insufficiency as patients may not present with the classic risk factors, signs, symptoms, and electrolyte derangements. [ABSTRACT FROM AUTHOR]

Background: Synchronous occurrence of prostate cancer (PCa) and renal cell carcinoma (RCC) is uncommon. RCC has a higher tendency to metastasize to the adrenal glands, renal hilar, and retroperitoneal lymph nodes compared to PCa. To date, there are no documented cases existing where metastatic tumors in these regions, observed in patients concurrently with PCa and RCC, have originated from the PCa rather than the RCC. Case presentation: In this case report, we described a 67-year-old male presented with dysuria for two months and left lower extremity edema for three days. Percutaneous biopsies revealed synchronous primary RCC and PCa. However, the origin of the metastatic tumors, especially those involving the adrenal glands, renal hilum, and retroperitoneal regions, remained undetermined. Subsequent surgical procedures identified that the metastatic lesions originated from the PCa, while the RCC was localized. Ultimately, the patient with metastatic hormone-sensitive prostate cancer (mHSPC) received combination therapy with rezvilutamide and goserelin, which resulted in a satisfactory treatment response. Conclusion: In patients with concurrent PCa and RCC, metastatic lesions in the adrenal glands, renal hilar, and retroperitoneal lymph nodes may also originate from the PCa. Accurate identification of the primary tumor and proper staging are critical for the appropriate management of patients with multiple primary malignancies with concurrent metastases. [ABSTRACT FROM AUTHOR]

Adenomatoid tumors (ATs) are uncommon, benign tumors of mesothelial origin, most frequently found in the genital tracts of both sexes. Extragenital localization sites, such as adrenal glands, are extremely rare. Since patients with adrenal ATs have no obvious clinical symptoms, imaging examination has become important evidence for diagnosis. Although previous literature noted that the imaging findings of adrenal ATs were nonspecific, no relevant studies have confirmed this. We herein present two novel cases of adrenal ATs, confirmed by immunohistochemistry, and that were initially misdiagnosed as other, more common adrenal tumors based on clinical findings and preoperative imaging. Including our cases, we collected a total of 33 previously reported adrenal ATs and extracted all available imaging information from them, aiming to find some radiological characteristics of this rare tumor. Through the review, we identified some nonspecific imaging features of adrenal ATs; however, the final diagnosis still depends on pathology and immunohistochemistry results. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is integral for the treatment of neuroblastoma, the most common extracranial solid malignancy in children. Safely locating and resecting primary tumor and remote deposits of disease remains a significant challenge, resulting in high rates of complications and incomplete surgery, worsening outcomes. Intraoperative molecular imaging (IMI) uses targeted radioactive or fluorescent tracers to identify and visualize tumors intraoperatively. GD2 was selected as an IMI target, as it is highly overexpressed in neuroblastoma and minimally expressed in normal tissue. Methods: GD2 expression in neuroblastoma cell lines was measured by flow cytometry. DTPA and IRDye® 800CW were conjugated to anti-GD2 antibody to generate DTPA-αGD2-IR800. Binding affinity (Kd) of the antibody and the non-radiolabeled tracer were then measured by ELISA assay. Human neuroblastoma SK-N-BE(2) cells were surgically injected into the left adrenal gland of 3.5-5-week-old nude mice and the orthotopic xenograft tumors grew for 5 weeks. 111In-αGD2-IR800 or isotype control tracer was administered via tail vein injection. After 4 and 6 days, mice were euthanized and gamma and fluorescence biodistributions were measured using a gamma counter and ImageJ analysis of acquired SPY-PHI fluorescence images of resected organs (including tumor, contralateral adrenal, kidneys, liver, muscle, blood, and others). Organ uptake was compared by one-way ANOVA (with a separate analysis for each tracer/day combination), and if significant, Sidak's multiple comparison test was used to compare the uptake of each organ to the tumor. Handheld tools were also used to detect and visualize tumor in situ, and to assess for residual disease following non-guided resection. Results: 111In-αGD2-IR800 was successfully synthesized with 0.75-2.0 DTPA and 2–3 IRDye® 800CW per antibody and retained adequate antigen-binding (Kd = 2.39 nM for aGD2 vs. 21.31 nM for DTPA-aGD2-IR800). The anti-GD2 tracer demonstrated antigen-specific uptake in mice with human neuroblastoma xenografts (gamma biodistribution tumor-to-blood ratios of 3.87 and 3.88 on days 4 and 6 with anti-GD2 tracer), while isotype control tracer did not accumulate (0.414 and 0.514 on days 4 and 6). Probe accumulation in xenografts was detected and visualized using widely available operative tools (Neoprobe® and SPY-PHI camera) and facilitated detection ofputative residual disease in the resection cavity following unguided resection. Conclusions: We have developed a dual-labeled anti-GD2 antibody-based tracer that incorporates In-111 and IRDye® 800CW for radio- and fluorescence-guided surgery, respectively. The tracer adequately binds to GD2, specifically accumulates in GD2-expressing xenograft tumors, and enables tumor visualization with a hand-held NIR camera. These results encourage the development of 111In-αGD2-IR800 for future use in children with neuroblastoma, with the goal of improving patient safety, completeness of resection, and overall patient outcomes. [ABSTRACT FROM AUTHOR]

In this study, a D‐shaped, extremely sensitive surface plasmon resonance (SPR) sensor with a blue shift characteristic is proposed that can be used to identify various malignant cancer cells. A sensing layer made of titanium is inserted to produce intense sensitivity. For the simulation and numerical evaluation of the proposed biosensor, we used the finite element method (FEM) and the COMSOL Multiphysics 5.6 software. To regulate how much light passes through the sensor, which incites the released electrons at the surface of the plasmonic material, air holes in different radii are used. The characteristics that make our proposed sensor superior to other D‐shaped SPR sensors are—it gives an excellent amplitude sensitivity (AS) of 200 RIU−1 also ensures extremely high wavelength sensitivity (WS) spanning from 34,350 to 42,145 nm/RIU with an outstanding spectral resolution of 2.37 × 10−6 RIU. Furthermore, the R2 (0.9966) value is also extremely close to 1 which ensures the quality of our sensor regarding its performance. The given sensor is tailored for four vital human cancers, which are blood cancer, skin cancer, cervical cancer, and adrenal gland cancer. Here, optimization of the structural geometric parameters, plasmonic materials, and material thickness are also conducted in search of the best functionality of the sensor. The offered structure, nonetheless, can be an obvious prologue in the case of the crucial human cancer detection platform due to its mild sensing performances. [ABSTRACT FROM AUTHOR]

Some studies have reported that the gut microbiota can influence adrenal-related hormone levels. However, the causal effects of the gut microbiota on adrenal function remain unknown. Therefore, we employed a two-sample Mendelian randomization (MR) study to systematically investigate the impact of gut microbiota on the function of different regions of the adrenal gland. The summary statistics for gut microbiota and adrenal-related hormones used in the two-sample MR analysis were derived from publicly available genome-wide association studies (GWAS). In the MR analysis, inverse variance weighting (IVW) was used as the primary method, with MR-Egger, weighted median, and cML-MA serving as supplementary methods for causal inference. Sensitivity analyses such as the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used to assess pleiotropy and heterogeneity. We identified 27 causal relationships between 23 gut microbiota and adrenal function using the IVW method. Among these, Sellimonas enhanced the function of the adrenal cortex reticularis zone (beta = 0.008, 95% CI: 0.002–0.013, P = 0.0057). The cML-MA method supported our estimate (beta = 0.009, 95% CI: 0.004–0.013, P = 2 × 10− 4). Parasutterella, Sutterella, and Anaerofilum affect the functioning of different regions of the adrenal gland. Notably, pleiotropy was not observed. Our findings revealed that the gut microbiota is causally associated with adrenal function. This enhances our understanding of the gut-microbiota-brain axis and provides assistance in the early diagnosis and treatment of adrenal-related diseases in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Primary aldosteronism is characterized by high plasma aldosterone and low renin. The plasma aldosterone-to-renin ratio is recommended for screening. Severe hydronephrosis leads to renal parenchymal ischemia, resulting in increased renin secretion. Since nonsuppression of renin may cause a negative result in the aldosterone-to-renin ratio test, severe hydronephrosis and primary aldosteronism occurring simultaneously in a patient are challenging to diagnose. Case presentation: A 54-year-old Chinese man of Han ethnicity was diagnosed with hypertension and severe hypokalemia (minimum 1.57 mmol/L) 13 years prior, and was also diagnosed with severe hydronephrosis due to congenital ureteral stenosis on the left side. His clinical features suggested primary aldosteronism, but the aldosterone-to-renin ratio result of the patient was negative every time he underwent the primary aldosteronism screening test. No further treatment for primary aldosteronism was performed, which led the patient to suffer from severe hypokalemia, such that he was taking 12–15 g/day potassium chloride orally to keep his blood potassium between 3.0 and 3.5 mmol/L (reference value, 3.5–5.5 mmol/L) for 13 years, and the patient needed to be hospitalized in the intensive care unit for rescue several times. At admission, although the aldosterone-to-renin ratio result of the patient was negative, we still did the saline stress test and captopril inhibition test, and the results showed that the plasma aldosterone level was not lower after the test than before the test. Adrenal enhanced computed tomography suggested an adenoma in the left adrenal gland, and the results of adrenal vein sampling suggested that the left side was the dominant side. Therefore, laparoscopic total resection of the left adrenal gland was performed, and 2 weeks later, the patient developed short-term renal function impairment and hyperkalemia, but his renal function and blood potassium returned to normal after treatment that included fluid rehydration. The patient's biochemical test results and clinical symptoms were completely normal after 1 year. Conclusion: We suggest that for patients with a high suspicion of primary aldosteronism in the clinic, comprehensive analysis must be performed in combination with clinical characteristic assessments, such as severe hydronephrosis, if renin is within the normal range or if the aldosterone-to-renin ratio result is negative at screening and diagnostic tests, and adrenal vein sampling should be performed if necessary. It can help avoid misdiagnoses and contribute to the treatment of patients with severe hydronephrosis and primary aldosteronism. [ABSTRACT FROM AUTHOR]

In this article, a theoretical study of Tamm plasmon based Refractive Index (RI) sensor for cancer cell detection has been proposed. The proposed sensor structure comprises of a thin titanium nitride (TiN) layer of thickness (dm = 30 nm) followed by a liquid cell of thickness (dL = 1500 nm) then followed by 16 pairs of semi-porous DBR (spDBR). The high and low index layers of spDBR constitute of silicon nitride (Si3N4) and porous Si3N4, respectively. We considered the porosity of low-index layer as 75%. The existence of Tamm plasmon between TiN and spDBR interface and the effect of porosity on the photonic band gap (PBG) of the spDBR have been studied as well. The impact of dm and dL on the reflection spectrum of the proposed structure has also been investigated. We investigated the detection of cancer-affected cells by replacing the liquid cell with respective cancer-affected cell and its corresponding normal cell, including blood cancer (Jurkat), cervical cancer (HeLa), adrenal gland cancer (PC12), two types of breast cancer (MDA-MB-231 and MCF-7), and skin cancer (Basal) cells. The proposed structure achieved the sensitivity, Q-factor, figure of merit, and detection limit of 752.85 nm/RIU, 131.64, 70.62 RIU−1, and 5 × 10−4 RIU, respectively. The proposed design can also be utilized in biological and gas sensing applications. [ABSTRACT FROM AUTHOR]

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS), presenting diagnostic challenges due to its rarity and its difficult clinical differentiation from other causes of CS. Here, we report the case of a 22-year-old female who developed classical symptoms of hypercortisolism including progressive weight gain, moon facies, and various skin manifestations. Despite biochemical screening confirming ACTH-independent CS, imaging modalities including computed tomography and magnetic resonance imaging showed normal adrenal gland morphology, complicating the localization of cortisol hypersecretion. Subsequent nuclear imaging methods were not indicative of ectopic cortisol production until adrenal vein sampling (AVS) conclusively identified the adrenal glands as the only possible source of cortisol hypersecretion. Eventually, bilateral adrenalectomy led to a significant improvement in symptoms. Pathological examination confirmed the diagnosis of PPNAD, and genetic testing revealed a mutation in the PRKAR1A gene associated with the Carney complex. This case highlights the importance of considering rare etiologies in hypercortisolism diagnosis and describes their challenging diagnostic workup and the utility of AVS in localizing cortisol hypersecretion in PPNAD patients. [ABSTRACT FROM AUTHOR]

Introduction: surgical procedures can lead to severe anxiety and stress in patients scheduled for surgery. Anxiety can cause stimulation leads to cardiovascular changes. Use of certain drugs like GABA mimetic like gabapentin are effective in control of anxiety. This will cause decrease in the level of cathacolamine release from adrenal gland cremafinn cell. Aims and objectives: To assess the level of the anxiety of the patient, to assess the level of the sedation levels of the patients, and to assess the hemodynamic responses produced by the body of the patients. Material and methods: This Prospective - Randomized study was conducted in the Anaesthesia Department in Rama Medical College Hospital and research centre, Kanpur from 25TH AUGUST 2022 TO 25TH MARCH 2024. The study was done on 120 patients who participated in the study. The samples were divided into two groups, 60 in each group, Group C (received clonidine) and Group G (received Gabapentin). Baseline vital signs such blood pressure, pulse rate, respiration rate, and oxygen saturation were recorded and these were recorded again after the intubation. Result: Anxiety score was significantly better in clonidine (group C) as compared with gabapentin (group G). Patient who received Gabapentin have more raise in SPO2 level than clonidine. Oral Gabapentin attenuated increase in heart rate, SPO2 and MAP than oral gabapentin. Conclusion: showed that oral clonidine can be used safely and efficiently to obtund the hemodynamic alterations related with laryngoscopy and endotracheal intubation. It was discovered that clonidine was more successful than gabapentin at reducing hemodynamic reactions to the procedures of intubation and laryngoscopy. [ABSTRACT FROM AUTHOR]

Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications. [ABSTRACT FROM AUTHOR]

In this report, we describe a very rare case of metastatic epithelioid hemangio‐endothelioma (EHE) originating from other organs such as the lung and requiring craniotomy due to subsequent hemorrhage. A 50‐year‐old man was diagnosed with EHE in the bilateral lungs, the mediastinum, and the right adrenal gland 8 years earlier. One year earlier, he had developed spinal metastasis. Six months earlier, a screening brain MRI had revealed multiple brain metastases of tumor. He developed subcortical hemorrhage from the tumor in the right parietal lobe and successfully underwent removal of hematoma and tumor. Histopathological examinations revealed EHE. Metastatic EHE is very rare but may be at high risk of intracranial hemorrhage. It is quite important to consider the possibility of brain metastasis and subsequent bleeding when treating patients with EHE. [ABSTRACT FROM AUTHOR]

Laparoscopic adrenalectomy is worldwide currently considered the gold standard technique for patients suffering from benign lesions. There has been an increasing number of robotic-assisted adrenalectomies in the last decade due to the systematic further development of minimally invasive surgery resulting in the implementation of robot-assisted surgery. Interestingly, the available studies show some perioperative advantages for robotic surgery but overall the current evidence is weak and there are economic aspects that are not negligible. Therefore, further high-quality studies about robotic-assisted adrenalectomy are mandatory to strengthen the current evidence. [ABSTRACT FROM AUTHOR]

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion‐induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high‐resolution free‐breathing upper abdominal MRI at 7 T with a large field of view. Free‐breathing 3D gradient‐recalled echo (GRE) water‐excited radial stack‐of‐stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6–24.8 kg/m2) at 7 T using an eight‐channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time‐interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B1 shims, based on a 23‐s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free‐induction decay navigator signals, respiratory‐gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm3. Two experienced radiologists rated the image quality and the impact of B1 inhomogeneity and motion‐related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7‐T acquisitions demonstrated increases in signal‐to‐noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free‐breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T. [ABSTRACT FROM AUTHOR]

Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary ACTH levels. Stress-induced total plasma corticosterone levels were increased, whereas the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor knock-out animals, compared to wild-type littermates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall, our data demonstrate that, in mice, tonic androgen receptor activation affects CBG levels in conjunction with effects on gene expression and HPA-axis reactivity. [ABSTRACT FROM AUTHOR]

Heat stress is a substantial environmental challenge that adversely affect health and performance. This study aimed to investigate the effect of advanced short-term dietary supplementation of probiotics or vitamin C on serum biochemical parameters, antioxidant status, and radiographic bone density in heat-stressed rats. A 48 male albino rat were randomly allocated into six groups: Control, Heat stress, Probiotics, Probiotics+Heat stress, Vitamin C, Vitamin C+Heat stress group. Rats in supplementation groups received probiotics or ascorbic acid orally from week 1 to 8. Heat stress groups were subjected to elevated temperature (42±1 °C and relative humidity 65±2%) 60 minutes daily for 4 weeks starting from week 5 to 8, while other groups were maintained under standard laboratory conditions. Heat stress resulted in increased serum ALT, AST, urea and creatinine (P<0.001), decreased calcium, increased phosphorus and osteocalcin (P<0.001), increased serum MDA, decreased TAC (P<0.001), decreased radiographic bone density (P<0.001) compared to other groups. Histopathological examination of liver, kidney and adrenal glands reflected the ongoing heat-stress damage. Administration of probiotics and ascorbic acid demonstrated substantial protection, suggesting their potential efficacy against heat stress. The obtained findings hold promise for the development of novel strategies to enhance heat stress resilience in animals. [ABSTRACT FROM AUTHOR]

Context The search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas. Objective To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS). Methods We investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS. Results Double IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (χ2 = 22.492, P <.001). Conclusion NGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of patients with aldosterone-producing adenomas. [ABSTRACT FROM AUTHOR]

This study describes the formation of single‐chain polymer dots (Pdots) via ultrasonic emulsification of nonionic donor‐acceptor‐donor type (D–A–D) alkoxy thiophene–benzobisthiadiazole‐based conjugated polymers (Poly BT) with amphiphilic cetyltrimethylammonium bromide (CTAB). The methodology yields Pdots with a high cationic surface charge (+56.5 mV ± 9.5) and average hydrodynamic radius of 12 nm. Optical characterization reveals that these Pdots emit near‐infrared (NIR) light at a maximum wavelength of 860 nm owing to their conjugated polymer backbone consisting of D–A–D monomers. Both colloidal and optical properties of these Pdots make them promising fluorescence emissive probes for bioimaging applications. The significant advantage of positively charged Pdots is demonstrated in diffusion‐limited mediums such as tissues, utilizing human epithelial breast adenocarcinoma, ATCC HTB‐22 (MCF‐7), human bone marrow neuroblastoma, ATCC CRL‐2266 (SH‐SY5Y), and rat adrenal gland pheochromocytoma, CRL‐1721 (PC‐12) tumor spheroid models. Fluorescence microscopy analysis of tumor spheroids from MCF‐7, SH‐SY5Y, and PC‐12 cell lines reveals the intensity profile of Pdots, confirming extensive penetration into the central regions of the models. Moreover, a comparison with mitochondria staining dye reveals an overlap between the regions stained by Pdots and the dye in all three tumor spheroid models. These results suggest that single‐chain D–A–D type Pdots, cationized via CTAB, exhibit long‐range mean free path of penetration (≈1 µm) in dense mediums and tumors. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Adrenal gland incidentalomas (AGIs) are found in up to 5% of cross‐sectional images. However, rates of guideline‐based workup for AGIs are notoriously low. We sought to determine if a natural language processing (NLP)‐informed AGI clinic could improve the rates of indicated biochemical evaluation and adrenal‐specific imaging.An NLP algorithm was created to detect clinically significant adrenal nodules from radiology reports of cross‐sectional images at an academic institution. The NLP algorithm was applied to scans occurring between June 2020 and July 2021 to form a baseline cohort. The NLP algorithm was re‐applied to scans from August 2021 to February 2023 and identified patients were invited to join an outpatient clinic dedicated to AGIs. Patients evaluated in the clinic from March 2022 to February 2023 were included in the intervention cohort. Statistical analysis utilized chi‐square, t‐test, and a multivariable logistic regression.The baseline and intervention cohorts included 1784 and 322 unique patients, respectively. Patients in the intervention cohort were more likely to be female (59% vs. 51%, p = 0.01), be younger (60 ± 13.1 vs. 64 ± 13.2 years, p < 0.001), have smaller nodules (1.7 cm, IQR 1.4–2.1 vs. 1.8 cm, IQR 1.4–2.5 cm, p = 0.017), have had biochemical workup (99% vs. 13%, p < 0.001), and have had adrenal‐specific imaging (40% vs. 11%, p < 0.001). In a multivariable analysis, intervention cohort patients were significantly more likely to have had biochemical workup (odds ratio ,OR 1209, confidence interval ,CI 434–5117, p < 0.001) and adrenal‐specific imaging (OR 8.89, CI 6.42–12.4, p < 0.001).The implementation of an NLP‐informed AGI clinic was associated with a seven‐fold increase in biochemical workup and a three‐fold increase in adrenal‐specific imaging in participating patients. [ABSTRACT FROM AUTHOR]

Adrenal gland metastases from malignant melanoma are a common but poorly characterised condition. Their lack of consistent clinical features and poor response to immune checkpoint inhibitors pose a significant diagnostic and therapeutic challenge to practitioners. This case report describes a 78-year-old male with no prior history of melanoma presenting with nonspecific abdominal symptoms and unintentional weight loss who was found to have undifferentiated bilateral adrenal gland metastases from malignant melanoma. Despite ongoing investigations, the primary site of the adrenal gland metastases remained unknown, prompting the consideration of primary adrenal melanoma as a diagnosis. The patient underwent four cycles of treatment with immune checkpoint inhibitors, nivolumab and ipilimumab, followed by maintenance therapy and subsequent adrenal metastasectomy. Despite therapeutic efforts, the patient's tumour was resistant to treatment and became undifferentiated. The patient continued with palliative care until his death, more than three years after the onset of symptoms. The clinical features, pathophysiology, diagnosis, treatment, and prognosis of this patient's disease are discussed in detail to help inform the management of similar cases. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia is an autosomal recessive disorder caused by complete or partial defects in one of the several steroidogenic enzymes involved in synthesizing of cortisol from cholesterol in the adrenal gland. Prompt and proper treatment of the disease would reduce symptoms and the level of androgens in patients. The present study aimed to evaluate the demographic characteristics and clinical findings of these patients. This retrospective investigation was conducted in 146 patients with congenital adrenal hyperplasia participated. Their clinical and paraclinical findings were accurately recorded in the file and extracted from the records. Among all 146 patients, 119(81.5 %) was 21-OH Deficiency type;11-OH Deficiency type was 13(8.9 %), 10(6.8 %) was 3β-HSD type, StAR was 2(1.4 %) and 17 alpha(α)-hydroxylase Deficiency was 2(1.4 %). The mean age of disease onset in these patients was 2.45 ± 1.16 years. Macropenis was the most frequent clinical finding in 39 cases of 64 boys (60.9 %), and Clitoromgaly was the most clinical presentation in 40 cases of 82 girls (48.7 %). The levels of testosterone, dehydroepiandrosterone sulfate, and 17-OHP significantly decreased in the last visit compared to the initial diagnosis. Based on the clinical findings in every infant or child with ambiguous genitalia, macropenis, clitoromegaly, hirsutism, and premature pubarche, we should consider congenital adrenal hyperplasia. Prompt and proper treatment and disease control would reduce symptoms and the level of androgens in patients. [ABSTRACT FROM AUTHOR]

Background Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied. Methods We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents. Results Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G > A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess. Conclusions We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A. [ABSTRACT FROM AUTHOR]

Background Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. Methods We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography—tandem mass spectrometry (LC—MS/MS) techniques were employed. Results Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC—MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. Conclusion This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) and pheochromocytoma (PCC) are malignancies originating from distinct layers of the adrenal gland. ACCs arise from the adrenal cortex, are often detected at advanced stages and are associated with poor prognosis. PCCs are mostly benign, arise from the adrenal medulla and have a variable prognosis, with 10% of PCCs resulting in metastasis. Genetic background strongly influences metastasis of PCCs, and no reliable biomarkers that predict metastatic behavior exist to date. Current therapeutic strategies for both ACCs and PCCs are overall limited. Thus, novel preclinical models and drug screening approaches need to be established to aid in the identification of more promising drugs and treatment schemes. In this review, we summarize the currently available human and murine cell lines for both tumor entities. [ABSTRACT FROM AUTHOR]

We studied the application of CT texture analysis in adrenal incidentalomas with baseline characteristics of benignity that are highly suggestive of adenoma to find whether there is a correlation between the extracted features and clinical data. Patients with hormonal hypersecretion may require medical attention, even if it does not cause any symptoms. A total of 206 patients affected by adrenal incidentaloma were retrospectively enrolled and divided into non-functioning adrenal adenomas (NFAIs, n = 115) and mild autonomous cortisol secretion (MACS, n = 91). A total of 136 texture parameters were extracted in the unenhanced phase for each volume of interest (VOI). Random Forest was used in the training and validation cohorts to test the accuracy of CT textural features and cortisol-related comorbidities in identifying MACS patients. Twelve parameters were retained in the Random Forest radiomic model, and in the validation cohort, a high specificity (81%) and positive predictive value (74%) were achieved. Notably, if the clinical data were added to the model, the results did not differ. Radiomic analysis of adrenal incidentalomas, in unenhanced CT scans, could screen with a good specificity those patients who will need a further endocrinological evaluation for mild autonomous cortisol secretion, regardless of the clinical information about the cortisol-related comorbidities. [ABSTRACT FROM AUTHOR]

Bilateral adrenal tumors are a rare pathology, increasingly detected due to the widespread use of diagnostic imaging procedures such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). These changes can be either malignant or benign, with the potential for autonomous hormone production. Historically, tuberculosis was a leading cause of bilateral adrenal changes due to lower socio-economic status and poor hygiene. In this case, the patient was diagnosed with hypertension at 38 years old, and initial considerations included secondary endocrine causes of hypertension, specifically primary aldosteronism. CT imaging revealed bilaterally enlarged adrenal glands with multiple nodular changes showing absolute and relative washout indices characteristic of adenomas, with the largest measuring 17 x 23 mm on the right and 21 x 23 mm on the left. The patient had a history of hypokalemia, with the lowest recorded potassium level being 3.3 mmol/L. She reported spontaneous bruising on her arms and legs and weight gain in the abdominal area. Testing indicated the presence of ACTH-independent hypercortisolism. To precisely localize cortisol hypersecretion, adrenal vein sampling (AVS) was performed. [ABSTRACT FROM AUTHOR]

Biallelic variants of steroidogenic acute regulatory protein (STAR/STARD1) may cause primary adrenal insufficiency and 46,XY disorder of sex development. STAR plays a pivotal role in transporting cholesterol into mitochondria where cholesterol serves as an essential substrate for initiating steroid biosynthesis by its conversion to pregnenolone. Generally, loss-of-function mutations of STAR cause the classic form of lipoid congenital adrenal hyperplasia (LCAH) where steroidogenesis of the adrenal cortex and the gonads is severely affected. By contrast, partial activity of STAR causes a less severe phenotype, the non-classic LCAH, which is characterized by later onset and initial manifestation with isolated adrenal insufficiency only. Disease-causing STAR variants are very rare. Numerous variants of all types have been described worldwide. Prevailing variants have been reported from Japan and Korea and in some population clusters where STAR is more common. Genotype–phenotype correlation is pretty good for STAR variants. While the exact mechanisms of cholesterol transport into mitochondria for steroidogenesis are still under investigation, the important role of STAR in this process is evident by inactivating STAR variants causing LCAH. The mechanism of disease with STAR deficiency is best described by a two-hit model: the first hit relates to impaired cholesterol import into mitochondria and thus lack of substrate for all steroid hormone biosynthesis; the second hit then relates to massive cytoplasmic lipid overload (evidenced by typically enlarged and fatty adrenal glands) leading to cell death and organ destruction. This review summarizes phenotype and genotype characteristics of human STAR variants found through the ClinVar database. [ABSTRACT FROM AUTHOR]

Adrenalectomy is the gold standard for canine adrenal tumours, but not always recommended due to patient age, underlying conditions and perioperative mortality. Ethanol ablation is an alternative in human medicine for poor surgical candidates. A 13‐year‐old neutered female toy‐poodle with hypercortisolism presented with severe haematuria. Ultrasonography revealed left adrenal and right kidney tumours. Due to high surgical risk, simultaneous laparotomic right nephroureterectomy and ethanol ablation of the left adrenal tumour were performed. Post‐ethanol injection complications included transient hypertension and arrhythmia, which resolved spontaneously. The adrenal tumour size decreased within 2.5 months, and cortisol levels normalised within 8 days, remaining stable for 12 months. No hypercortisolism signs were observed without trilostane until death from renal insufficiency. Autopsy showed that the ablated left adrenal gland was an adrenocortical tumour and had shrunk. Ethanol ablation may be a feasible alternative to adrenalectomy for high‐risk canine patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. Study Design: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two‐dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. Results: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. Conclusions: Adrenal sparing correlates with a relative increase in adrenal measurements and function. Synopsis: The adrenal gland of intrauterine growth‐restricted fetuses is relatively larger compared with controls and its function is enhanced. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors. [ABSTRACT FROM AUTHOR]

Chronic stress is a significant factor affecting modern society, with profound implications for both physical and mental health. Central to the stress response is cortisol, a glucocorticoid hormone produced by the adrenal glands. While cortisol release is adaptive in acute stress, prolonged exposure to elevated levels can result in adverse effects. This manuscript explores the neurobiological implications of chronic stress and its impact on metabolic dysregulation, particularly in the context of inflammatory bowel diseases (IBDs). The hypothalamic–pituitary–adrenal (HPA) axis regulates cortisol production, which influences metabolism, immune response, and neurobiology. Elevated cortisol levels are associated with the development and exacerbation of metabolic disorders like IBD and contribute to neurodegenerative processes, including cognitive impairments and increased susceptibility to psychiatric conditions. The interaction between cortisol and its receptors, particularly glucocorticoid receptors, underscores the complexity of these effects. This review aims to elucidate the mechanisms through which chronic stress and cortisol dysregulation impact metabolic health and neurobiological function, providing insights into potential therapeutic strategies for mitigating these effects. [ABSTRACT FROM AUTHOR]

Background: Cystic lesions in the adrenal glands are infrequent and unusual occurrences, with only a handful of cases documented thus far. These lesions come in various types, exhibiting diverse origins and sharing similar clinical presentations, ranging from benign to potentially malignant cystic growths. Typically, they do not cause symptoms, but in some rare instances, they may lead to abdominal discomfort or a sense of fullness. Due to their rarity, there is ongoing debate surrounding the most effective approach for managing adrenal cysts. Case Presentation: This case report presents a case of a 36-year-old female who presented with a history of abdominal pain and was incidentally found to have a right adrenal cyst during a CT scan. She exhibited no additional symptoms, such as hypertension, headache, or palpitations. Laparoscopic right adrenalectomy was performed, successfully removing the cystic mass without complications. Preoperative laboratory tests, including endocrine function tests, were unremarkable. Imaging studies, including ultrasound and contrast-enhanced CT, characterized the cyst as a large, well-circumscribed, low-attenuated structure with peripheral calcifications, distinct from the right suprarenal gland. Gross examination revealed a collapsed cyst measuring 7 x 3 cm with a smooth inner wall, and the right adrenal gland measured 4 x 2.5 cm. The histological analysis identified the lesion as an adrenal pseudocyst with a fibrous wall containing focal dystrophic microcalcifications and embedded adrenocortical cells. No endothelial lining, eosinophils, or parasites were present. The patient's postoperative course was uneventful, and she was discharged in stable condition the following day. Conclusion: This case demonstrates the effective management of a large adrenal pseudocyst through laparoscopic adrenalectomy, resulting in a successful outcome without complications. Comprehensive imaging and histopathological evaluation were crucial in confirming the diagnosis and guiding treatment. [ABSTRACT FROM AUTHOR]

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Background and Objectives: Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the case of a 36-year-old patient who presented to a medical facility at the end of 2019 with an enlarged right testicle. A unilateral orchofuniculectomy was performed, and a mass measuring 30 cm was removed. During histological examination, testicular seminoma pT2, R0, was diagnosed. An abdominal computed tomography (CT) scan showed a 6.4 cm × 6.8 cm × 6.7 cm tumour in the right kidney and a metastatic-like lesion in the right adrenal gland. A right nephrectomy and an adrenalectomy and paraaortic and paracaval lymphadenectomies were performed. A histological evaluation confirmed the presence of clear-cell renal carcinoma pT2aR0 G2, adrenal hyperplasia, and seminoma metastases in the removed lymph node. Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out. Three years after the last cycle of chemotherapy, a follow-up CT scan showed metastases in the left kidney, the right ischium, and the right lung. A well-differentiated clear-cell carcinoma G1 of the left kidney and metastasis of clear-cell carcinoma G2 in the right ischium were confirmed after the biopsy, and no tumour lesions were found in the lung tissue specimen. Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria. Genetic testing was performed, and the following genes were analysed: VHL, BAP1, CHEK2, FH, MET, MUTYH, APC, and STK11. The testing did not reveal any pathogenic or potentially pathogenic mutations or sequence changes of unknown clinical significance in the genes analysed. Conclusions: According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis. [ABSTRACT FROM AUTHOR]