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Background: Hypoxia is a critical physiological and pathological condition known to influence various cellular processes, including steroidogenesis. While previous studies, including our own, have highlighted the regulatory effects of Hypoxia-Inducible Factor 1α (HIF1α) on steroid production, the specific molecular mechanisms remain poorly understood. This study investigates the role of hypoxia and HIF1α in steroid biosynthesis across multiple experimental models during acute exposure to low oxygen levels. Methods: To assess the extent to which acute hypoxia modulates steroidogenesis, we employed several approaches, including the Y1 adrenocortical cell line, and a conditional HIF1α-deficient mouse line in the adrenal cortex. We focused on various regulatory patterns that may critically suppress steroidogenesis. Results: In Y1 cells, hypoxia upregulated specific microRNAs in a HIF1α-dependent manner, resulting in the suppression of mRNA levels of critical steroidogenic enzymes and a subsequent reduction in steroid hormone production. The hypoxia/HIF1α-dependent induction of these microRNAs and the consequent modulation of steroid production were confirmed in vivo. Notably, using our adrenocortical-specific HIF1α-deficient mouse line, we demonstrated that the increase in miRNA expression in vivo is also directly HIF1α-dependent, while the regulation of steroidogenic enzymes (e.g., StAR and Cyp11a1) and steroid production occurs at the level of protein translation, revealing an unexpected layer of control under hypoxic/HIF1 α conditions in vivo. Conclusions: These findings elucidate the molecular mechanisms underlying acute hypoxia/HIF1α-induced changes in steroid biosynthesis and may also be useful in developing new strategies for various steroid hormone pathologies. [ABSTRACT FROM AUTHOR]

Background: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of Cushing's syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 are responsible for 20–25% of apparently sporadic PBMAH cases and 80% of familial presentations. ARMC5 screening is now routinely performed for PBMAH patients and families. Based on literature review and own observation, this study aims to give an overview of both published and unpublished ARMC5 genetic alterations and to compile the available evidence to discriminate pathogenic from benign variants. Results: 146 different germline variants (110 previously published and 36 novel) are identified, including 46% missense substitutions, 45% truncating variants, 3% affecting splice sites, 4% in-frame variants and 2% large deletions. In addition to the germline events, somatic 16p loss-of-heterozygosity and 104 different somatic events are described. The pathogenicity of ARMC5 variants is established on the basis of their frequency in the general population, in silico predictions, familial segregation and tumor DNA sequencing. Conclusions: This is the first extensive review of ARMC5 pathogenic variants. It shows that they are spread on the whole coding sequence. This is a valuable resource for genetic investigations of PBMAH and will help the interpretation of new missense substitutions that are continuously identified. [ABSTRACT FROM AUTHOR]

Endocrine surgery in multimorbid, frail and geriatric patients is increasing, is often urgent and characterized by special risk constellations. Successful parathyroid gland surgery nearly always results in a marked improvement, irrespective of the specific risk profile of the patient. Except for critical intubation and mediastinal interventions in the risk profile, surgery of the thyroid glands is predominantly beneficial and justifiable even in frail patients. For surgery of the adrenal glands and for gastroenteropancreatic neuroendocrine tumors (GEP-NET), the expected extension of resection, the underlying disease or the grading are decisive for whether alternative treatment measures or surveillance appear to be more beneficial for patients at risk. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of a 3D V-Net-based segmentation model of adrenal lesions in characterizing adrenal glands as normal or abnormal. Methods: A total of 1086 CT image series with focal adrenal lesions were retrospectively collected, annotated, and used for the training of the adrenal lesion segmentation model. The dice similarity coefficient (DSC) of the test set was used to evaluate the segmentation performance. The other cohort, consisting of 959 patients with pathologically confirmed adrenal lesions (external validation dataset 1), was included for validation of the classification performance of this model. Then, another consecutive cohort of patients with a history of malignancy (N = 479) was used for validation in the screening population (external validation dataset 2). Parameters of sensitivity, accuracy, etc., were used, and the performance of the model was compared to the radiology report in these validation scenes. Results: The DSC of the test set of the segmentation model was 0.900 (0.810–0.965) (median (interquartile range)). The model showed sensitivities and accuracies of 99.7%, 98.3% and 87.2%, 62.2% in external validation datasets 1 and 2, respectively. It showed no significant difference comparing to radiology reports in external validation datasets 1 and lesion-containing groups of external validation datasets 2 (p = 1.000 and p > 0.05, respectively). Conclusion: The 3D V-Net-based segmentation model of adrenal lesions can be used for the binary classification of adrenal glands. Critical relevance statement: A 3D V-Net-based segmentation model of adrenal lesions can be used for the detection of abnormalities of adrenal glands, with a high accuracy in the pre-surgical scene as well as a high sensitivity in the screening scene. Key Points: Adrenal lesions may be prone to inter-observer variability in routine diagnostic workflow. The study developed a 3D V-Net-based segmentation model of adrenal lesions with DSC 0.900 in the test set. The model showed high sensitivity and accuracy of abnormalities detection in different scenes. [ABSTRACT FROM AUTHOR]

This study investigates the effects of alcoholic (AB) and non-alcoholic beer (NAB) consumption on blood pressure and the activity of enzymes regulating the renin–angiotensin system (RAS) in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHRs), with WKY rats used as normotensive controls for SHRs. The RAS is crucial for long-term blood pressure regulation, with angiotensin II (AngII) being a potent vasoconstrictor. The aim was to explore the biochemical mechanisms by which beer might influence cardiovascular health. WKY and SHRs were divided into groups receiving tap water (TW), non-alcoholic beer (NAB), alcoholic beer (AB), TW or NAB and TW or AB for 12 weeks. Systolic blood pressure (SBP), body weight, and biochemical parameters (electrolytes, glucose, renal and liver function, lipid profile) were monitored, and the RAS enzyme activity in serum and various tissues was analyzed. Beer consumption, regardless of alcohol content, did not significantly affect SBP or body weight. However, NAB and AB altered the serum electrolyte levels in both strains. AB consumption increased liver enzyme activity. Significant changes were observed in the RAS enzyme activity across tissues, varying by strain, beer type, and tissue. Moderate beer consumption did not elevate blood pressure in WKY or SHRs. Nevertheless, beer modulated RAS-regulating enzyme activities, indicating potential impacts on cardiovascular homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the adrenal gland size of fetuses with congenital heart diseases (CHD) and normal fetuses.In this cross-sectional prospective study we measured the fetal adrenal gland size (total width, cortex width, medulla width, adrenal gland ratio of total width divided by medulla width) in 62 fetuses with CHD and 62 gestational-age-matched controls between 20 + 0 and 39 + 3 weeks of gestation. First, we clustered three CHD subgroups: CHD group_1 with a normal outflow tract (n=7), CHD group_2 with an altered outflow tract and anterograde flow in the ascending aorta (n=39) and CHD group_3 with an altered outflow tract and retrograde flow in the ascending aorta (n=16). In a second step, we summed up all CHD cases with outflow tract anomalies to CHD group_2 + 3 (n=55). Each group was compared to their matched controls.Prenatally, fetuses affected by CHD with outflow tract alterations show an elevated adrenal gland ratio (total width/medulla width) compared to normal fetuses (p<0.001). This finding applies to both subgroups of outflow tract alterations with anterograde (p<0.001) and retrograde perfusion of the ascending aorta (p<0.001).Fetuses affected by CHD with an altered outflow tract show a relatively larger cortex of the adrenal gland compared to normal fetuses. The results of this study suggest that haemodynamic changes during fetal maturation cause an elevated metabolic stress level that may be responsible for an enlarged adrenal gland ratio. [ABSTRACT FROM AUTHOR]

Brain and muscle ARNT-Like 1 (BMAL1) is a circadian clock transcription factor that regulates physiological functions. Male adrenal-specific Bmal1 (ASCre/+::Bmal1) KO mice displayed blunted serum corticosterone rhythms, altered blood pressure rhythm, and altered timing of eating, but there is a lack of knowledge in females. This study investigates the role of adrenal BMAL1 in renal electrolyte handling and urinary aldosterone levels in response to low salt in male and female mice. Mice were placed in metabolic cages to measure 12-h urinary aldosterone after a standard diet and 7 days low-salt diet, as well as daily body weight, 12-h food and water intake, and renal sodium and potassium balance. Adrenal glands and kidneys were collected at ZT0 or ZT12 to measure the expression of aldosterone synthesis genes and clock genes. Compared with littermate controls, ASCre/+::Bmal1 KO male and female mice displayed increased urinary aldosterone in response to a low-salt diet, although mRNA expression of aldosterone synthesis genes was decreased. Timing of food intake was altered in ASCre/+::Bmal1 KO male and female mice, with a blunted night/day ratio. ASCre/+::Bmal1 KO female mice displayed decreases in renal sodium excretion in response to low salt, but both male and female KO mice had changes in sodium balance that were time-of-day-dependent. In addition, sex differences were found in adrenal and kidney clock gene expression. Notably, this study highlights sex differences in clock gene expression that could contribute to sex differences in physiological functions. NEW & NOTEWORTHY: Our findings highlight the importance of sex as well as time-of-day in understanding the role of the circadian clock in the regulation of homeostasis. Time-of-day is a key biological variable that is often ignored in research, particularly in preclinical rodent studies. Our findings demonstrate important differences in several measures at 6 AM compared with 6 PM. Consideration of time-of-day is critical for the translation of findings in nocturnal rodent physiology to diurnal human physiology. [ABSTRACT FROM AUTHOR]

The sustained consumption of sucrose-rich diet has deleterious effects on the adrenal cortex, impairing its steroidogenic capacity. As hemin treatment has been shown to exert cytoprotective effects (e.g., by heme oxygenase 1 induction), our main goal was to analyze the adrenocortical function in rats treated with diet and hemin. Male Wistar rats fed standard chow and 30%sucrose in the drinking water (SRD) for 12 weeks ad libitum were injected with hemin for the last 2 weeks of treatment. mRNA and proteins were analyzed by real-time polymerase chain reaction, western blot or immunofluorescence, and corticosterone levels were assessed by radioimmunoassay. A decrease in lipid peroxides and an increase in the activity of catalase were detected in the SRD + H group. Moreover, pro-inflammatory markers (TNF-a, IL1b, CXCL10, NOS2, NALP3 and MCP1), IBA1+/ED1+ cells and NFκβ activation were still elevated in tissues from SRD + H-treated rats, whereas an increase in markers of macrophages with the M2-phenotype (ARG1, MRC1 and TGFb) was also shown. Activation of ER stress in SRD-treated rats (CHOP, XBP1s and P58IPK) and the induction of apoptosis (TUNEL and the BAX/BCL2 mRNA ratio) were also attenuated by hemin. Finally, ACTH-stimulated glucocorticoid production, significantly decreased in SRD-treated rats, was upregulated by hemin. The consumption of SRD involves exposure of tissues to a higher metabolic load that could generate oxidative stress and a pro-inflammatory state. Deleterious consequences of these processes could account for the significant decrease in the ACTH-induced corticosterone output from the gland. By correcting these effects, hemin treatment was able to restore the hormoneinduced adrenocortical response. [ABSTRACT FROM AUTHOR]

The article in the journal "Cytopathology" discusses a challenging case of small-cell melanoma with isolated adrenal metastasis. A 53-year-old man presented with right hypochondrium pain, weight loss, and loss of appetite. The diagnosis was confirmed through immunocytochemistry, highlighting the deceptive cytomorphologic features of small-cell melanoma. The patient received palliative radiotherapy and chemotherapy but unfortunately succumbed to the disease, showcasing the aggressive nature of small-cell melanoma metastases. [Extracted from the article]

Background: Quantifying urinary catecholamines and metanephrines is essential for the clinical screening and diagnosis of neuroendocrine tumours. HPLC with electrochemical detection (HPLC-ECD) is commonly used for this type of analysis but requires extensive sample cleanup. Simple and rapid dilute-and-shoot LC–multiple-reaction monitoring (MRM)-MS assays have been developed for quantitating these analytes in urine but have not yet been validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Methods: A simple dilute-and-shoot sample preparation without derivatization was used. C18 RP-UPLC-MRM-MS and positive-ion ESI were used, usually with two transitions per analyte being monitored. Certified deuterated internal standards were used for each analyte. Results: This assay was validated according to the CLSI C62-A guidelines, including accuracy/trueness, imprecision, sensitivity, specificity, carryover, stability, and linearity. The final MRM-MS method was compared to the established HPLC-ECD clinical chemistry reference method. The run time was reduced from 25 min to 5 min. Conclusions: A simple, robust, rapid, and cost-effective LC-MRM-MS assay for measuring urinary catecholamines and metanephrines was developed and validated according to the CLSI guidelines. This validated method requires minimal sample manipulation before analysis and provides sensitivity, specificity, and improved precision. The implementation of this assay in clinical laboratories will facilitate early and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Retroperitoneal laparoscopic adrenalectomy (RLA) is one of two laparoscopic procedures used to treat benign and malignant adrenal diseases. Obesity in patients undergoing minimally invasive adrenal surgery is a frequently discussed topic. Our meta-analysis aimed to provide updated evidence by comparing intraoperative and perioperative outcomes on non-obese (NOb) and obese (Ob) patients who underwent RLA due to benign or malignant disease. Materials and Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Web of Science (Science and Social Science Citation Index), and Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL)) databases were used to identify articles of interest. The meta-analysis was performed using RevMan [Computer program] Version 5.4. Results: The four included comparative studies (809 patients: 552 NOb versus 257 Ob) covered an approximately 15-year-study period (2007–2022). All the included studies were observational in nature. By comparing the Ob and NOb groups, shorter operative time and lower overall postoperative complication rates in the NOb population were recorded through the meta-analysis. Considering the subgroup analysis (BMI ≥ 30 kg/m2), just the operative time maintained statistical significance. Conclusions: Obesity did not appear to impact RLA safety and effectiveness. Due to important biases (small overall sample size and few analyzed events), the interpretation of our results must be a careful one. Later randomized and multi-center trials may help the confirmation of our results. [ABSTRACT FROM AUTHOR]

Scalding burns are a common form of thermal injury that often leads to systemic complications. Pro-inflammatory cytokines like interleukin-6 (IL-6) and the activation of signal transducer and activator of transcription 3 (STAT3) pathways have been linked to the pathophysiology of organ damage caused by burns. This study aimed to investigate the potential therapeutic effects of dexmedetomidine, an α2-adrenergic receptor agonist with anti-inflammatory properties, on the interplay of IL-6 and STAT3 pathways in adrenal gland damage following scalding burns in rats. Twenty-eight rats were divided randomly into four groups. Rats in group 1 (n=7, control) were given only 0.9% intraperitoneal (i.p.) NaCl. Rats in group 2 (n=7, DEX) were exposed to 25°C water for 17 s on day 1 and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days; for rats in group 3 (n=7, Burn), boiling water of 94°C was applied inside for 17 s. Rats in group 4 (n=7, Burn+DEX) were exposed to 94°C water for 17 s and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days. Adrenal gland tissues were histopathological examined, and STAT3, IL-6, and TUNEL staining were performed using immunohistochemically. Our results revealed that scalding burns increased IL-6 and STAT3 expression in the adrenal glands of rats. Histological analysis demonstrated that dexmedetomidine administration ameliorated adrenal gland damage and reduced inflammatory cell infiltration. Our findings suggest that dexmedetomidine protects the adrenal glands in scalding burns. This protection appears to be mediated, at least in part, by its modulation of IL-6 and STAT3 pathways. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytomas and paragangliomas are rare chromaffin cell-derived tumors characterized by catecholamine-secreting activity. Pheochromocytomas account for 1.7% of pediatric hypertension cases. Surgical resection, the definitive pheochromocytoma treatment, carries risks of hemodynamic instability and cardiovascular complications. Nevertheless, mortality rates decreased significantly in the latter half of the 20th century due to effective perioperative blood pressure (BP) management. The literature on BP management tailored to pediatric pheochromocytoma is limited, while the sustained hypertension rate in this population is high (up to 90%) and related to a high risk of intraoperative complications. In this narrative review, we provide up-to-date recommendations regarding BP management to minimize perioperative comorbidities in children with pheochromocytoma. Summary: Antihypertensive agents, primarily alpha (α)-blockers, should be promptly administered for suspected pheochromocytoma. Beta (β)-blockers may be introduced thereafter to counteract reflex tachycardia. The patient must be salt- and water-replete preoperation. Intraoperatively, stable hemodynamics should be ensured during anesthesia and surgery, and short-acting intravenous medications and resuscitation fluid should be supplied. Postoperatively, patients should be admitted to the pediatric intensive care unit for close monitoring for at least 24–48 h. Genetic testing is recommended for all pheochromocytoma patients. Identifying underlying mutations, like in succinate dehydrogenase subunit B, which is linked to a higher risk of multifocality and metastasis, is imperative for tailoring treatment strategies and prognostication. Key Messages: Achieving optimal outcomes in pediatric pheochromocytoma relies on preoperative BP optimization with appropriate antihypertensive agents, intraoperative hemodynamic stability, and postoperative routine long-term follow-up to monitor for complications, recurrence, and metastasis. Future research should prioritize well-designed prospective multicenter studies with adequate sample sizes and, where feasible, randomized controlled trials with standardized protocols and appropriate endpoints. These studies should focus on the efficacy and safety of preoperative nonselective versus selective α-blockers, whether as monotherapy or combined with other medications (e.g., calcium channel blockers and/or β-blockers), or treatment without preoperative anti-hypertensives. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a rare type of tumor, and UPS originating in the adrenal gland is even rarer. Up to now, there have been no reports in English literature of UPS originating from the adrenal gland. This case report presents a 44-year-old female patient with UPS of the adrenal gland, who has shown no signs of recurrence or metastasis half a year after undergoing resection of a left adrenal tumor. A retrospective analysis of the patient's diagnosis and treatment process is conducted, with the aim of providing a reference for the diagnosis and treatment of adrenal UPS. [ABSTRACT FROM AUTHOR]

Calcineurin inhibitors (CnIs) are effective immunosuppressants with decades of accumulated experience in treating immune disorders and, most notably, solid organ transplantation. While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI‐associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern. The occurrence of several ion imbalances alongside hypertension was also noted early on, indicating the involvement of the renin–angiotensin–aldosterone system (RAAS) in CnI‐mediated toxicity. However, the literature in this field is crowded with conflicting reports from clinical trials as well as studies using animal and invitro models. With this review, we aim to provide a structured and updated overview of the physiological and pathophysiological evidence supporting the involvement of the classical RAAS in CnI‐associated toxicity. [ABSTRACT FROM AUTHOR]

With the outbreak of the COVID-19 pandemic, the scientific community has directed its attention towards studying the impact of the causative agent, SARS-CoV-2, on the endocrine system. It has been proven that the virus exhibits organotropism towards the cortex of the adrenal glands, causing tissue damage and hormonal dysfunction. The aim of this exposition is to address the question of whether SARS-CoV-2 causes disruptions in the hormonal regulation of glucocorticoid hormones. Based on a thorough review of the current literature, it is suggested that the virus could potentially directly damage the hypothalamus, leading to a disruption in the regulation of the hypothalamic-pituitary-adrenal axis. The decrease in cortisol secretion is a secondary effect. As a result, there is a loss of stress-induced cortisol elevation due to the inflammatory process and an increased risk of adrenal crisis. On the other hand, inflammatory cytokines synthesized during the inflammatory process could stimulate cortisol secretion through an ACTH-independent mechanism. The magnitude of the biological response is influenced by the newly emerged resistance of cortisol receptors, disturbances in intracellular cortisol signaling, and dysregulation between ACTH and cortisol secretion. The detailed study of functional changes in cortisol secretion in response to SARS-CoV-2-associated inflammation provides a new horizon for scientific research following recovery from COVID-19.

We present the case of a 22-year-old male with a left adrenal pheochromocytoma, initially diagnosed during a workup for thoracic pain. The patient's tumor was refractory to medical management, and surgical resection was ruled out due to high cardiovascular risk, stemming from cyanotic congenital heart disease, aortic aneurysm, and factor VII deficiency. The patient underwent adrenal artery embolization (AAE) as a salvage treatment. Following the procedure, there was an initial reduction in hypertensive crises and biochemical markers, with plasma normetanephrine levels decreasing from 1490 pg/mL to 313 pg/mL. However, over subsequent months, the patient experienced symptom recurrence, and biochemical relapse occurred, with normetanephrine levels rising to 742 pg/mL by 3 months postprocedure. This case highlights the potential for AAE to provide short-term symptom relief and biochemical response; nevertheless, it may not be an effective long-term curative option. More collaborative and prospective studies are needed to assess its success and efficacy.

Hydatid cyst is a zoonotic disease rarely involving the adrenal glands, even in areas where the disease is endemic. The purpose of this article is to present the clinical and imaging findings of adrenal hydatid cysts, along with a comprehensive literature review of related research. Here we report a rare case of an 18-year-old male with a right adrenal cystic lesion showing characteristic features of a hydatid cyst on ultrasonography and computed tomography, which turned out to be an adrenal hydatid cyst after surgical excision. In conclusion, when a cystic lesion is detected in the suprarenal regions, adrenal hydatid cysts should be considered in differential diagnosis, especially in patients who live in or have come from endemic areas. Medical imaging can play a crucial role in diagnosing, managing, and postsurgical assessment of this condition.

Background and purpose: Primary adrenal intravascular large B-cell lymphoma (IVLBCL) is rare and highly aggressive. Unfortunately, comprehensive and sufficient understanding of the disease is lacking. This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL. Methods: Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology, Fudan University Shanghai Cancer Center. The clinical and histopathological features, immunophenotype, treatment and prognosis were analyzed. The molecular genetic characteristics were detected using next-generation sequencing (NGS). This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (Ethics number: 050432-4-2307E). Results: All of the 5 patients were male, with median age 52 years (ranged 50-82 years). Two cases had low-grade fever, 1 case had abdominal pain, 1 case was found by physical examination, and the information of the remaining one was unknown. Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases. On initial diagnosis, imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose (FDG) uptake. Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case. Morphologically, large atypical lymphocytes were confined to blood vessels, and fibrinous necrosis was observed in some cases. Immunohistochemical study revealed that CD20 was positive in all cases. Ki-67 proliferation index was high, all above 80%. 80% (4/5) of the cases were of non-germinal-center B-cell-like (non-GCB) phenotype, 100% (4/4) of the cases had MYC/BCL2 double expression. Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases. Follow-up data were available in 3 patients. One patient who underwent only surgical resection died 5 months after diagnosis, one achieved complete remission after surgery plus R-CHOP, and the other diagnosed by biopsy achieved a partial remission after R-CHOP. The 1-year overall survival rate was 66.7%, and overall survival was 5-87 months. NGS testing in 1 case showed missense mutations in MYD88 V217F, TP53, CDH1, ARID1B, MSH3, MLH3, PTPRK, CD22 and FLCN. Conclusion: Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male. The majority of our patients were non-GCB phenotype, often accompanied by MYC/BCL2 double expression, and MYD88 non-L265P mutation was detected. Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity. It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease, which might not only help with early diagnosis, timely treatment and improvement of prognosis, but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

Giant adrenal myelolipoma (AML) may cause severe symptoms. In contrast to the previous reports, laparoscopy may play a pivotal role in the management of giant AML. This report aims to discuss a case of giant AML managed successfully by laparoscopy. A 63-year-old male was found to have a giant (12 × 10 × 8 cm) left AML during a workup for left lower chest pain on imaging. laparoscopic excision of a left adrenal gland with the lesion was performed under general anesthesia. The patient was discharged from the hospital after 3 days uneventfully. AML is a benign tumor that is characterized by the presence of adipose tissue and hematopoietic elements. Myelolipomas are typically asymptomatic. AML diagnosis is based on imaging and blood workup. Small asymptomatic AML is usually managed conservatively, while symptomatic AML is managed with surgery. Even though an open approach is the standard option, laparoscopy, as a minimally invasive technique, in some centers may replace laparotomy. Laparoscopy can be a successful method for managing AML, even when they are large in size.

Neuroendocrine carcinoma (NEC) presence in the adrenal glands is rare. Neuroendocrine carcinoma manifests across a wide range of clinical presentations, from asymptomatic cases to those characterized by hormone overproduction or the tumor's mass effect. We report a 48-year-old male referred by a urology specialist with a chief complaint of right-sided back pain for the past 6 months accompanied by nausea, vomiting, and sharp stabbing headaches. The patient had a history of right adrenalectomy surgery. Elevated blood pressure of 150/110 mmHg, and no abnormalities found. The radiologist found a solid lesion and cyst at the lower pole of the right kidney and observed multiple recurrent tumors in the right adrenal on the MRI examination. The biopsy revealed poorly differentiated carcinoma and adrenocortical carcinoma tissue on the second biopsy 2 months later. The patient was diagnosed with neuroendocrine carcinoma; the patient underwent a biopsy guided by CT, followed by a pathological assessment (PA). The surgeon carried out the tumor removal surgery and performed an immunohistochemical (IHC) analysis. A 3-month follow-up is planned to evaluate the potential need for adjuvant chemotherapy. The case underscores the importance of accurate pathological diagnosis and multimodal management in recurrent adrenal tumors, particularly when considering NEC as a differential diagnosis.

Abstract Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size.

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]

Background: Primary aldosteronism (PA) is a common cause of endocrine hypertension, characterized by excessive aldosterone secretion leading to hypertension, hypokalemia, and metabolic alkalosis. While historically diagnosed based on this classic triad of symptoms, current understanding reveals a more nuanced presentation. This study aimed to investigate the prevalence of PA-associated diseases in a large German population. Methods: Medical records from the IQVIATM Disease Analyzer database were analyzed retrospectively. PA patients (n = 860) were matched with non-PA individuals (n = 4300) by age and sex. Associations between PA and predefined chronic diseases were examined using multivariable logistic regression. Results: PA was significantly associated with hypokalemia (7.8% vs. 1.6%, odds ratio (OR): 3.45; 95% confidence intervals (CIs): 2.41–4.96), hypertension (56.1% vs. 28.5%; OR: 2.37; 95% CIs: 2.00–2.81), hepatic steatosis (11.3% vs. 3.0%; OR: 1.85; 95% CIs: 1.34–2.57), gout (8.3% vs. 2.2%; OR: 1.64; 95% CIs: 1.15–2.35), chronic kidney disease (6.3% vs. 2.2%; OR: 1.59; 95% CIs: 1.10–2.31), diabetes mellitus not otherwise specified (7.9% vs. 2.9%; OR: 1.49; 95% CIs: 1.06–2.09), obesity (13.5% vs. 5.1%; OR: 1.38; 95% CIs: 1.05–1.82), and depression (14.8% vs. 6.2%; OR: 1.37; 95% CIs: 1.07–1.77). Conclusions: While the study design had limitations, including reliance on ICD codes for diagnosis, these findings underscore the critical need for early detection and personalized management strategies for PA to reduce associated risks and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size. [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]

The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary cells. Currently, the mechanisms by which C5a impacts adrenal cell function are poorly understood. The PC12 cell model was used to examine the cellular effects following treatment with recombinant rat C5a. The levels of caspase activation and cell death, protein kinase signaling pathway activation, and changes in inflammatory protein expression were examined following treatment with C5a. There was an increase in apoptosis of PC12 cells following treatment with high-dose C5a. Ten inflammatory proteins, primarily involved in apoptosis, cell survival, and cell proliferation, were upregulated following treatment with high-dose C5a. Five inflammatory proteins, involved primarily in chemotaxis and anti-inflammatory functions, were downregulated. The ERK/MAPK, p38/MAPK, JNK/MAPK, and AKT protein kinase signaling pathways were upregulated in a C5aR-dependent manner. These results demonstrate an apoptotic effect and cellular signaling effect of high-dose C5a. Taken together, the overall data suggest that high levels of C5a may play a role in C5aR-dependent apoptosis of adrenal medullary cells in sepsis. [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]

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]

Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin–angiotensin–aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Aging progresses through the interaction of metabolic processes, including changes in the immune and endocrine systems. Glucocorticoids (GCs), which are regulated by the hypothalamic–pituitary–adrenal (HPA) axis, play an important role in regulating metabolism and immune responses. However, the age‐related changes in the secretion mechanisms of GCs remain elusive. Here, we found that corticosterone (CORT) secretion follows a circadian rhythm in young mice, whereas it oversecreted throughout the day in aged mice >18 months old, resulting in the disappearance of diurnal variation. Furthermore, senescent cells progressively accumulated in the zF of the adrenal gland as mice aged beyond 18 months. This accumulation was accompanied by an increase in the number of Ad4BP/SF1 (SF1), a key transcription factor, strongly expressing cells (SF1‐high positive: HP). Removal of senescent cells with senolytics, dasatinib, and quercetin resulted in the reduction of the number of SF1‐HP cells and recovery of CORT diurnal oscillation in 24‐month‐old mice. Similarly, administration of a neutralizing antibody against IL1β, which was found to be strongly expressed in the adrenocortical cells of the zF, resulted in a marked decrease in SF1‐HP cells and restoration of the CORT circadian rhythm. Our findings suggest that the disappearance of CORT diurnal oscillation is a characteristic of aging individuals and is caused by the secretion of IL1β, one of the SASPs, from senescent cells that accumulate in the zF of the adrenal cortex. These findings provide a novel insight into aging. Age‐related hypersecretory GCs could be a potential therapeutic target for aging‐related diseases. [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]

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]

Schwannomas are benign, generally indolent tumors of neural crest origin and comprise the most common histologic tumor of peripheral nerves. Schwannomas are a rare histology for retroperitoneal tumors and very rare histologic findings for tumors of the adrenal gland with fewer than 50 cases in the reported literature. Here we present a case report of a non-hormonally functional but metabolically active adrenal tumor with indeterminate imaging characteristics with final pathology showing a 6.1 cm adrenal schwannoma as well as historical institutional pathology review revealing two additional cases.

ABSTRACT Introduction: Advances in imaging methods have led to an increasingly frequent diagnosis of adrenal gland lesions as incidental findings. Despite progress in this field, there is still limited information regarding the epidemiology of the clinical and metabolic profile of patients with adrenal incidentaloma (AI). The objective is analyze the epidemiology of adrenal tumors at Gaffrée e Guinle University Hospital (HUGG) and compare it with data from the literature. Method: This is a cross-sectional study that included patients of any gender and age who was treated at HUGG for adrenal tumors. Results: The following variables were evaluated: age, gender, functionality, benignity, and size. We also analyzed the metabolic profile of patients with AI, specifically those with mild autonomy cortisol secretion. Out of 31 patients with adrenal tumors, 68% were female. The mean age was 55 years with a standard deviation of ±16.2. 54% of the sample had adrenal incidentalomas. 93.6% of the sample had benign cases. Among the adrenal incidentalomas, 53% were non-functioning. In patients with adrenal tumors, only 10% had metabolic syndrome, while in patients with mild autonomous cortisol secretion, this number rose to 17%. Conclusion: The sample of patients with adrenal tumors and incidentaloma at HUGG presented a prevalence of metabolic complications similar to that found in the literature.

Abstract Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn’s syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach. The former presents very significant side effects whereas the latter can be ineffective in cases where the adrenal disorder reoccurs in the remaining contralateral adrenal gland. Due to the limitations of existing treatment methods, minimally invasive treatment options like microwave ablation (MWA) have received significant attention for treating adrenal gland disorders. A precise comprehension of the dielectric properties of human adrenal glands will help to tailor energy delivery for MWA therapy, thus offering the potential to optimise treatments and minimise damage to surrounding tissues. This study reports the ex vivo dielectric properties of human adrenal glands, including the cortex, medulla, capsule, and tumours, based on the data obtained from four patients (diagnosed with Conn’s syndrome, Cushing's syndrome, and Pheochromocytoma) who underwent unilateral adrenalectomy at the University Hospital Galway, Ireland. An open-ended coaxial probe measurement technique was used to measure the dielectric properties for a frequency range of 0.5–8.5 GHz. The dielectric properties were fitted using a two-pole Debye model, and a weighted least squares method was employed to optimise the model parameters. Moreover, the dielectric properties of adrenal tissues and tumours were compared across frequencies commonly used in MWA, including 915 MHz, 2.45 GHz, and 5.8 GHz. The study found that the dielectric properties of adrenal tumours were influenced by the presence of lipid-rich adenomas, and the dielectric properties of Cushing's syndrome tumour were lowest in comparison to the tumours in patients diagnosed with Conn's syndrome and Pheochromocytoma. Furthermore, a notable difference was observed in the dielectric properties of the medulla and cortex among patients diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These findings have significant implications for the diagnosis and treatment of adrenal tumours, including the optimisation of MWA therapy for precise ablation of adrenal masses.

Adrenal leiomyomas are rare and often reported as Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) in association with EBV infection in immunocompromised patients. We experienced a case of right adrenal leiomyoma that was incidentally found in a man in his 70s. Computed Tomography (CT) showed a well-circumscribed mass of 3.1 cm in diameter in the right adrenal gland, which increased to 4.9 cm in diameter over 1 year. Preoperative diagnosis was difficult due to the lack of specific imaging findings. He had a history of diffuse large B-cell lymphoma (DLBCL) 8 years ago, and EBV had been detected in his blood. EBV-encoded small RNA(EBER) in situ hybridization (EBER-ISH) of the right adrenal leiomyoma was positive, and the final diagnosis was EBV-associated leiomyoma.

Abstract The study of adrenal disorders is a key component of scientific research, driven by the complex innervation, unique structure, and essential functions of the adrenal glands. This review explores the use of non-traditional animal models for studying congenital adrenal hyperplasia. It highlights the advantages, limitations, and relevance of these models, including domestic ferrets, dogs, guinea pigs, golden hamsters, pigs, and spiny mice. We provide a detailed analysis of the histological structure, steroidogenesis pathways, and genetic characteristics of these animal models. The morphological and functional similarities between the adrenal glands of spiny mice and humans highlight their potential as an important avenue for future research.