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Background Hypothesis/Objectives Animals Methods Results Conclusions and Clinical Importance Functionality of human adrenal tumors is inferred by CYP11B1 (cortisol synthase) expression, CYP11B2 (aldosterone synthase) expression, or both.Nonfunctional canine adrenal tumors have low expression of steroidogenic enzymes, whereas aldosterone‐producing tumors express CYP11B, and cortisol‐producing tumors express both CYP11B and CYP17.Twenty‐two client‐owned dogs with adrenocortical tumors (ACT) (8 nonfunctional, 7‐cortisol producing, 2 aldosterone‐producing and 5 functional noncortisol producing) and 2 dogs with normal adrenal glands.Retrospective case series. Adrenal functionality was determined from clinical signs and endocrine testing. CYP11A1, CYP11B, CYP17, and HSD3B2 expression was detected by immunohistochemistry on formalin‐fixed paraffin‐embedded adrenal tissue. Protein expression was semiquantified by 2 blinded observers using H‐scoring (results reported as median [range]) and compared in nonfunctional and cortisol‐producing adrenal tumors by Mann‐Whitney U tests.CYP11A1, CYP11B, and HSD3B2 were present within all cortical layers of normal adrenal glands, and CYP17 was expressed within the zona fasciculata and zona reticularis. Expression of CYP11A1 (191.25 [97.5‐270] vs. 175 [102.5‐295] P = .69), CYP11B (190 [130‐265] vs. 147.5 [95‐202.5]; P = .07), CYP17 (177.5 [87.5‐240] vs. 247.5 [55‐292.5]; P = .40), and HSD3B2 (230 [47.5‐295] vs. 277.5 [67.5‐295]; P = .34) were not significantly different between cortisol‐producing and nonfunctional ACT.Our findings suggest it is not possible to determine functionality of canine ACT by immunohistochemistry for steroidogenic enzymes. Tumor size cannot be used to infer functionality of adrenal tumors. [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 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]

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]

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]

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]

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]

Primary breast Burkitt lymphoma (PB-BL) is an exceedingly rare form of primary breast lymphoma. Ultrasonography is the preferred modality for diagnosing breast diseases; however, the ultrasonic features of Burkitt lymphoma have rarely been reported. Herein, we report a case of ultrasonically diagnosed bilateral PB-BL in a lactating patient and present a literature review. A 28-year-old female patient experienced bilateral breast engorgement starting more than a month after childbirth. At three months postpartum, the patient experienced extreme bilateral breast engorgement, with the skin appearing dark purple and jaundiced. Based on the imaging diagnosis, pathological, immunohistochemical, and molecular biological findings, she was diagnosed with Burkitt lymphoma involves bilateral breasts, right adrenal glands, uterus, and multiple bones. After 4 cycles of combination chemotherapy, the tumor basically disappeared, and then after autologous stem cell transplantation and one cycle of combination chemotherapy, the patient is generally in good condition and is under follow-up. We found that the ultrasonic characteristics of PB-BL are different from those of common breast cancer or lactation mastitis. PB-BL lesions are often multiple, large masses, and even involve the whole breast. The characteristic reticular structures are common in lesions, and irregular hyperechoic masses can be seen around it. The mass has abundant peripheral and internal blood flow signals, but internal calcification and attenuated posterior echoes of masses are rarely observed. Thus, the ultrasonic features of breast Burkitt lymphoma are somewhat specific and understanding these features is conducive to its early identification. [ABSTRACT FROM AUTHOR]

Cushing's syndrome is a rare, multisystemic disease caused by chronic exposure to supraphysiologic levels of cortisol. Prolonged hypercortisolism is associated with significant multisystem morbidity and mortality and decreased quality of life. Diagnosis of Cushing's syndrome is often delayed by several years due to its insidiously progressive course, diverse clinical presentation, overlap of symptoms with many common conditions, and testing complexity. Exogenous glucocorticoid use must be excluded as the primary etiology. Excessive endogenous cortisol production can be caused by an overproduction of adrenocorticotropic hormone (ACTH) through pituitary tumors or ectopic sources (ACTH-dependent cases), or it can be caused by autonomous cortisol overproduction by the adrenal glands (ACTH-independent cases). The recommended diagnostic approach includes appropriate screening, confirmation of hypercortisolism, and determination of etiology. First-line treatment is surgical removal of the source of cortisol overproduction. Lifelong posttherapy monitoring is required to treat comorbidities and detect recurrence. [ABSTRACT FROM AUTHOR]

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]

We present the case of a 32-year-old pregnant woman in the 32 + 3 weeks of pregnancy who presented to the hospital with an exacerbation of pain in the right flank. The diagnostic evaluation revealed the presence of severe anemia and a spontaneous adrenal hemorrhage (SAH) in the right adrenal gland. The patient was transferred to the Perinatology, Obstetrics and Gynecology Clinic with the intention of undergoing preterm childbirth. However, the doctors made a risky decision to wait until week 37 and to terminate the pregnancy at that point. The decision was right, as a cesarean section was performed without complications, and the patient gave birth to a healthy child. Spontaneous adrenal hemorrhage (SAH) is a rare condition, defined as spontaneous hemorrhage without trauma or anticoagulant therapy. Due to bleeding and damage to the adrenal cortex, SAH can lead to adrenal insufficiency. Because of its non-specific symptoms and potentially fatal outcomes for the patient and fetus, it should be considered during diagnostics. [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]

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Purpose: This study aimed to clarify surgical complications associated with open surgery for congenital diaphragmatic hernia (CDH). Methods: We performed an exploratory data analysis of the clinical characteristics of surgical complications of neonates with CDH who underwent laparotomy or thoracotomy between 2006 and 2021. Data of these patients were obtained from the database of the Japanese CDH Study Group. Results: Among 1,111 neonates with left or right CDH, 852 underwent open surgery (laparotomy or thoracotomy). Of these 852 neonates, 51 had the following surgical complications: organ injury (n = 48; 6% of open surgeries); circulatory failure caused by changes in the organ location (n = 2); and skin burns (n = 1). Injured organs included the spleen (n = 30; 62% of organ injuries), liver (n = 7), lungs (n = 4), intestine (n = 4), adrenal gland (n = 2), and thoracic wall (n = 2). Fourteen of the patients who experienced organ injury required a blood transfusion (2% of open surgeries). The adjusted odds ratio of splenic injury for patients with non-direct closure of the diaphragm was 2.2 (95% confidence interval, 1.1–4.9). Conclusion: Of the patients who underwent open surgery for CDH, 2% experienced organ injury that required a blood transfusion. Non-direct closure of the diaphragmatic defect was a risk factor for splenic injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Cushing syndrome (CS) is the result of chronic exposure to glucocorticoid excess. CS in children is most often caused by the administration of exogenous steroids. Endogenous CS is rare in the paediatric population and is caused mainly by tumours of the pituitary and adrenal glands, with ectopic sources being extraordinarily rare before the age of 18 years. In addition, children and young adults with CS present with different epidemiology, management issues, prognosis and outcomes than older adult patients. This complex disorder needs early diagnosis and management to avoid the significant morbidity and even mortality that can result from chronic untreated CS.In this review, we present the complex case of a 7‐year‐old boy with CS that highlights the diagnostic and management challenges of paediatric CS patients, including the considerations for genetic predisposition and life‐long consequences of CS in children and young adults.The diagnostic protocols for the evaluation of CS have been devised for adults and tested predominantly on adults. In this review, we discuss necessary modifications so that the testing can be adjusted for use in children. Additionally, pituitary adenomas in children are generally smaller and thus more difficult to recognize on pituitary imaging.The management of the case and its complexities underline the need for children with CS to be managed in a centre with experienced paediatric endocrinologists and skilled neurosurgeons both for their initial diagnosis and treatment as well as for their long‐term follow‐up and management. [ABSTRACT FROM AUTHOR]

Background: Myelolipoma is an uncommon benign tumor composed of mature adipose tissue and hematopoietic elements. These tumors generally affect the adrenal glands, with anomalous presentations being rare and with few cases described in the literature. Most myelolipomas are asymptomatic and discovered incidentally, either through imaging tests or at autopsies. However, depending on the location and size of the lesion, myelolipomas can cause symptoms of mass effect. This article aims to report a very rare presentation of a symptomatic primary myelolipoma affecting the ribs. Case presentation: A 21-year-old white female patient presented with a complaint of burning chest pain over 3 months, with gradual worsening in intensity, accompanied by a progressively growing bulge in the right thoracic wall. The patient underwent thoracotomy of the fifth and sixth ribs with complete excision of the lesion with a safety margin. Thoracic wall reconstruction was performed using a polypropylene mesh. The patient had a good postoperative course and was discharged on postoperative day 3. Histopathological examination revealed a histological image consistent with myelolipoma. Conclusions: This report underscores the importance of considering a myelolipoma diagnosis for tumor masses in the ribs. [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]

This article discusses a case of small-cell melanoma with isolated adrenal metastasis. The patient experienced symptoms such as pain, weight loss, and loss of appetite. Imaging tests revealed lesions in the adrenal gland and inguinal region. The article explores the diagnosis, immunocytochemical profile, metastasis rates, and genetic abnormalities associated with this type of tumor. It also emphasizes the challenges in diagnosing small-cell melanoma and the importance of immunocytochemistry in confirming the diagnosis. The text highlights the deceptive features of small-cell melanoma and identifies key mimics. [Extracted from the article]

A comparative analysis of morphological and functional changes in the adrenal glands after embolization of supplying arteries with Lifepearl microspheres (100±25 μm; Terumo) and with a solution of polidocanol (Aethoxysklerol, Kreussler Pharma) was performed in male Vietnamese Lop-Bellied pigs (n=20). The introduction of the microspheres into the arterial bed did not affect the adrenal parenchyma. However, the injection of the liquid sclerosing agent caused foci of productive inflammation leading to the formation of sclerotic tissue and reduction of the volume of glandular tissue. Administration of the sclerosant was accompanied by arterial hypotension, an indirect indication of a decrease in vasoactive hormone production by the adrenal cortex. These findings suggest that polidocanol can be used as an embolization agent for hyperplastic diseases of the adrenal cortex. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic–pituitary–adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE. [ABSTRACT FROM AUTHOR]

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation endproducts (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is a bisphenol A derivative that is widely used in the manufacturing of industrial and consumer products. The presented study was conducted to explore the adverse effects of BPF on the adrenal glands of rats. Toward this aim, twenty-eight male albino Wistar rats were randomly divided into four groups, each containing seven individuals. The animals were administered a vehicle (control) or BPF at 3 different doses comprising 20, 100, and 500 mg/kg of body weight (bw) via oral gavage for 28 days. Next, the effects of BPF on the gland were evaluated in terms of histopathological alterations, serum adrenocorticotropic hormone (ACTH) and cortisol levels, and the contents of reduced glutathione (GSH) and malondialdehyde (MDA). The zona fasciculata of the adrenal cortex showed prominent histopathological lesions such as vacuolar degeneration and necrotic degeneration in the experimental groups. BPF caused noticeable elevations in the serum ACTH and cortisol levels. Moreover, decreases in levels of GSH and increments in the contents of MDA were determined, indicating oxidative stress. In conclusion, BPF showed toxic effects on the adrenal gland that may result in disruptions in its vital functions in the body. The results herein suggest that attention should be paid to the utilization of BPF in manufacturing processes due to its harmful effects and risks to the health of organisms. [ABSTRACT FROM AUTHOR]

Calcineurin, protein phosphatase 2B (PP2B) or protein phosphatase 3 (PP3), is a calcium‐dependent serine/threonine protein phosphatase. Calcineurin is widely expressed in the kidney and regulates renal Na+ and K+ transport. In the thick ascending limb, calcineurin plays a role in inhibiting NKCC2 function by promoting the dephosphorylation of the cotransporter and an intracellular sorting receptor, called sorting‐related‐receptor‐with‐A‐type repeats (SORLA), is involved in modulating the effect of calcineurin on NKCC2. Calcineurin also participates in regulating thiazide‐sensitive NaCl‐cotransporter (NCC) in the distal convoluted tubule. The mechanisms by which calcineurin regulates NCC include directly dephosphorylation of NCC, regulating Kelch‐like‐3/CUL3 E3 ubiquitin–ligase complex, which is responsible for WNK (with‐no‐lysin‐kinases) ubiquitination, and inhibiting Kir4.1/Kir5.1, which determines NCC expression/activity. Finally, calcineurin is also involved in regulating ROMK (Kir1.1) channels in the cortical collecting duct and Cyp11 2 expression in adrenal zona glomerulosa. In summary, calcineurin is involved in the regulation of NKCC2, NCC, and inwardly rectifying K+ channels in the kidney, and it also plays a role in modulating aldosterone synthesis in adrenal gland, which regulates epithelial‐Na+‐channel expression/activity. Thus, application of calcineurin inhibitors (CNIs) is expected to abrupt calcineurin‐mediated regulation of transepithelial Na+ and K+ transport in the kidney. Consequently, CNIs cause hypertension, compromise renal K+ excretion, and induce hyperkalemia. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Maternal heat stress during late pregnancy can lead to intrauterine hyperthermia and affect fetal hypothalamic-pituitary-adrenal axis development and function. Herein, we investigated the effects of chronic environmental heat stress exposure of Holstein cows in the last 2 mo of gestation on their offspring's adrenal gland histomorphology and transcriptome. Cows in their last 54 ± 5 d of gestation were either heat stressed (housed under the shade of a freestall barn) or provided heat stress abatement via active cooling (via water soakers and fans) during a subtropical summer (temperature-humidity index >68). Respiration rate (RR) and skin temperature (ST) were elevated in heat-stressed dams relative to the cows with access to heat abatement (23 breaths/min and 2°C higher for RR and ST, respectively). Heifers born to heat-stressed cows experienced heat stress in utero (HS), whereas heifers born to actively cooled cows did not (CL). The adrenal gland was harvested from 6 heifers per group that were euthanized at birth (d 0; n = 12) or 1 wk after weaning (d 63; n = 12). Circulating cortisol was measured from blood samples collected weekly throughout the preweaning period. At d 63, heifers that experienced HS while developing in utero had heavier adrenal glands, with a greater total tissue surface area and thickness of the zona glomerulosa (ZG), fasciculata (ZF), and reticularis (ZR), compared with CL heifers. In addition, the adrenal gland of HS heifers had fewer cells in the ZG, more and larger cells in the ZF, and larger cells in the ZR, relative to CL heifers. Although no changes in circulating cortisol were observed through the preweaning period, the transcriptomic profile of the adrenal tissue was altered by fetal exposure to hyperthermia. Both at birth and on d 63, approximately 30 pathways were differentially expressed in the adrenal glands of HS heifers relative to CL. These pathways were associated with immune function, inflammation, prolactin signaling, cell function, and calcium transport. Upstream regulators significantly activated or inhibited in the adrenal glands of heifers exposed to intrauterine hyperthermia were identified. Maternal exposure to heat stress during late gestation caused an enlargement of their offspring's adrenal glands by inducing ZG and ZF cell hypertrophy, and caused gene expression changes. These phenotypic, histological, and molecular changes in the adrenal gland might lead to alterations in stress, immune, and metabolic responses later in life. [ABSTRACT FROM AUTHOR]

An innovative photonic crystal fiber (PCF) biosensor using surface plasmon resonance (SPR) to diagnose six distinct kinds of cancers (skin cancer, cervical cancer, adrenal gland cancer, blood cancer, and breast cancer types 1 and 2) in cells is demonstrated here and incorporates with two microchannels and a bimetallic configuration. The numerical analysis utilizes the finite element method (FEM) combined with perfectly matched layers (PML). The plasmonic material employed in the biosensor is gold (Au), and a supportive material, titanium dioxide (TiO2), is combined with Au. By combining these two materials, the sensor's performance is improved. The numerical calculations indicate that breast cancer type 2 has the highest wavelength sensitivity (24,285.71 nm/RIU) and amplitude sensitivity (3959 RIU−1). The rest of the cancer cells' wavelength sensitivities are 11,000.00 nm/RIU (skin cancer), 13,333.33 nm/RIU (cervical cancer), 15,000.00 nm/RIU (blood cancer), 17,142.85 nm/RIU (adrenal gland cancer), and 21,428.57 nm/RIU (breast cancer type 1). This advanced biosensor has several uses in biological sensing and medical technology, and it has the potential to revolutionize cancer identification and medical diagnosis. [ABSTRACT FROM AUTHOR]

The thymus, where T lymphocytes develop and mature, is sensitive to insults such as tissue ischemia or injury. The insults can cause thymic atrophy and compromise T-cell development, potentially impairing adaptive immunity. The objective of this study was to investigate whether myocardial infarction (MI) induces thymic injury to impair T lymphopoiesis and to uncover the underlying mechanisms. When compared with sham controls, MI mice at day 7 post-MI exhibited smaller thymus, lower cellularity, as well as less thymocytes at different developmental stages, indicative of T-lymphopoiesis impairment following MI. Accordingly, the spleen of MI mice has less T cells and recent thymic emigrants (RTEs), implying that the thymus of MI mice releases fewer mature thymocytes than sham controls. Interestingly, the secretory function of splenic T cells was not affected by MI. Further experiments showed that the reduction of thymocytes in MI mice was due to increased thymocyte apoptosis. Removal of adrenal glands by adrenalectomy (ADX) prevented MI-induced thymic injury and dysfunction, whereas corticosterone supplementation in ADX + MI mice reinduced thymic injury and dysfunction, indicating that glucocorticoids mediate thymic damage triggered by MI. Eosinophils play essential roles in thymic regeneration postirradiation, and eosinophil-deficient mice exhibit impaired thymic recovery after sublethal irradiation. Interestingly, the thymus was fully regenerated in both wild-type and eosinophil-deficient mice at day 14 post-MI, suggesting that eosinophils are not critical for thymus regeneration post-MI. In conclusion, our study demonstrates that MI-induced glucocorticoids trigger thymocyte apoptosis and impair T lymphopoiesis, resulting in less mature thymocyte release to the spleen. NEW & NOTEWORTHY: The thymus is essential for maintaining whole body T-cell output. Thymic injury can adversely affect T lymphopoiesis and T-cell immune response. This study demonstrates that MI induces thymocyte apoptosis and compromises T lymphopoiesis, resulting in fewer releases of mature thymocytes to the spleen. This process is mediated by glucocorticoids secreted by adrenal glands. Therefore, targeting glucocorticoids represents a novel approach to attenuate post-MI thymic injury. [ABSTRACT FROM AUTHOR]

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single‐nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular‐endothelial cells and cortical‐neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β‐catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single‐nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma‐specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal‐related pathologies. [ABSTRACT FROM AUTHOR]

This case report presents a 10-year-old patient diagnosed with pheochromocytoma/paraganglioma syndrome type 1 (PPGL1), underlined by a novel heterozygous pathogenic variant (c.154_161del, p.ser52Profster14) in the SDHD gene. Initially, the patient manifested symptoms unusual for pheochromocytoma, including polyuria and polydipsia; however, further diagnostic investigations revealed a pheochromocytoma (PCC) tumor in the adrenal gland. Subsequently, whole exome sequencing (WES) test identified a pathogenic frameshift variant in the SDHD gene, strongly suggestive of PPGL1. This study highlights the importance of considering atypical symptoms in diagnosing rare pediatric pheochromocytoma/paraganglioma tumors and underscores the value of genetic testing in identifying underlying genetic causes, thereby facilitating personalized management of the condition. [ABSTRACT FROM AUTHOR]

Bilateral adrenal masses, increasingly encountered in clinical practice, manifest across diverse contexts, including incidental discovery, malignancy staging, and targeted imaging after hormonal diagnosis of adrenal disorders. The spectrum encompasses various pathologies, such as cortical adenomas, macronodular adrenal disease, pheochromocytomas, myelolipomas, infiltrative disorders, and primary and secondary malignancies. Notably, not all masses in both adrenal glands necessarily share the same etiology, often exhibiting diverse causes. Recently, the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors updated guidelines, introduced a 4-option schema based on imaging, aiding in targeted hormonal testing and management. This "Approach to the Patient" review delves into the latest advancements in imaging, biochemical, and genetic approaches for the diagnostic and management nuances of bilateral adrenal masses. It provides insights and a contemporary framework for navigating the complexities associated with this clinical entity. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Carbimazole has disadvantages on different body organs, especially the thyroid gland and, rarely, the adrenal glands. Most studies have not suggested any solution or medication for ameliorating the noxious effects of drugs on the glands. Our study focused on the production of xylooligosaccharide (XOS), which, when coadministered with carbimazole, relieves the toxic effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity. This XOS produced by Aspergillus terreus xylanase was covalently immobilized using microbial Scleroglucan gel beads, which improved the immobilization yield, efficiency, and operational stability. Over a wide pH range (6–7.5), the covalent immobilization of xylanase on scleroglucan increased xylanase activity compared to that of its free form. Additionally, the reaction temperature was increased to 65 °C. However, the immobilized enzyme demonstrated superior thermal stability, sustaining 80.22% of its original activity at 60 °C for 120 min. Additionally, the full activity of the immobilized enzyme was sustained after 12 consecutive cycles, and the activity reached 78.33% after 18 cycles. After 41 days of storage at 4 °C, the immobilized enzyme was still active at approximately 98%. The immobilized enzyme has the capability to produce xylo-oligosaccharides (XOSs). Subsequently, these XOSs can be coadministered alongside carbimazole to mitigate the adverse effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity.

Tumors originating from soft tissues are uncommon, among these tumors, liposarcomas are the most frequent. These tumors remain asymptomatic for a long time, and only revealing themselves when they reach an important size. In such cases, treatment is difficult, requiring extensive surgery procedures that can excise several adjacent structures, potentially completed by adjuvant radiotherapy. Despite successful treatment, the recurrence rate remains very high. We report the case of a giant liposarcoma requiring a monobloc extensive resection involving the removal of the tumor, left kidney, left adrenal gland, and a portion of the posterior abdominal wall. [ABSTRACT FROM AUTHOR]

Objective: Carney complex is a rare autosomal dominant syndrome that has been shown to be associated with inactivation due to PRKAR1A mutations. We revealed a novel PRKAR1A gene mutation in Chinese patient with Carney complex and review the literature to enhance understanding of Carney complex. Case presentation: A 23-year-old Chinese male patient with a family history cardiac myxoma was admitted to our Department of Endocrinology because of central obesity and hyperpigmentation. Physical examination revealed a maximum blood pressure of 150/93mmHg, awaist circumference of 102cm, aweight of 70kg, a height of 170cm, and a BMI of 24.22kg/m2. Additionally, there was spotty skin pigmentation on the lip mucosa, purple striae on the abdomen, thin skin on both legs, and visible veins. Blood examination revealed hypercortisolemia, decreased adrenocorticotropic hormone (ACTH) levels and failure to suppress cortisol with lowand high-dose dexamethasone suppression tests.Magnetic resonance imaging (MRI) scan revealedmultiple small adrenal nodules and Retroperitoneal neurogenic tumor. Genetic testing showed a novel heterozygous mutation in exon 5 of PRKAR1A (c.500_;502 + 8delAAGGTAAGGGC). The patient underwent resection of the right adrenal gland and retroperitoneal neoplasms in 2020. Postoperative pathology following the right adrenal gland resection showed nodular hyperplasia of the adrenal cortex. The pathology from the retroperitoneal tumor resection revealed spindle cell tumors rich in pigment and cells. The patient was diagnosed as Carney complex according to Stratakis CA in 2001 guidelines. After long-term follow-up, the patient's condition was stable, with weight loss, waist circumference reduction, significantly lower cortisol levels, and normal blood lipids. Conclusion: This case reported a Carney complex in a Chinese patient, characterized clinically by non-ACTH-dependent Cushing's syndrome, familial recurrent cardiac myxomas, psammomatous melanotic schwannoma (PMS) and skin and mucosal pigmentation. A novel subtype of PRKAR1A mutation was discovered, which may affect the characteristics of the PRKAR1A protein and contribute to the development of Carney complex. [ABSTRACT FROM AUTHOR]

Background: Some observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear. Methods: This study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran's Q statistic was used to test for heterogeneity of instrumental variables. Results: The IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism. Conclusions: This two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota. [ABSTRACT FROM AUTHOR]

Introduction: While the influence of various factors on classical androgen synthesis in children and adolescents and its impact on puberty has been widely investigated, there appear to be gaps and contradictory findings regarding the association of overweight and obesity with the synthesis of adrenal-derived 11-oxygenated androgen (11-OA) serum levels. With this study, we aimed to examine how overweight and obesity affect 11-OA serum levels during puberty in a large cohort of children and adolescents. Methods: Our cohort comprised 1,054 healthy children aged 6–19 years providing serum samples at a total of 1,734 visits. Liquid chromatography-tandem mass spectrometry was used to quantify 11-ketotestosterone (11-KT), 11-ketoandrostendione (11-KA4), 11-β-hydroxytestosterone (11-OHT), 11-β-hydroxyandrostendione (11-OHA4), testosterone, androstenedione, and DHEAS. In addition, we assessed BMI-SDSs, skinfold thicknesses, and Tanner stages. The significance level α was set to α = 0.05. Results: Increases in 11-KT, 11-KA4, 11-OHT, and 11-OHA4 levels were observed in boys and girls during puberty. 11-KT (β = 0.2, p < 0.001), 11-KA4 (β = 0.16, p < 0.001), and 11-OHA4 (β = 0.12, p = 0.003) were positively correlated with BMI in boys aged 13 years and under. 11-KT (β = 0.1, p = 0.047) was positively correlated with BMI in girls aged 11 years and under. 11-OHT was positively correlated with BMI independent of age (boys 13 years and under: β = 0.17, p < 0.001; over 13 years: β = 0.14, p = 0.001; girls 11 years and under: β = 0.17, p < 0.001; over 11 years: β = 0.18, p < 0.001). Conclusion: We found increasing 11-OA serum levels throughout all Tanner stages. 11-OAs were observed to be associated with BMI and skinfold thickness, suggesting that overweight and obesity may be associated with pubertal alterations in 11-OA serum levels. [ABSTRACT FROM AUTHOR]