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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.

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Advances in the diagnosis and treatment of adrenocortical carcinoma (ACC), along with the development of new therapeutic and diagnostic methods, have prompted a team of experts to formulate the first Polish guidelines for managing ACC. This article presents the diagnostic and therapeutic recommendations resulting from the discussion of specialists from various medical specialities, who participated in a series of online meetings aimed at developing consistent and effective recommendations under the National Oncology Strategy. These guidelines aim to optimise ACC treatment in Poland through coordinated efforts of multidisciplinary specialist teams, ensuring an effective and modern approach.

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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.

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Background: Adrenocortical tumours (ACT) in children are part of the Li-Fraumeni cancer spectrum and are frequently associated with a germline TP53 pathogenic variant. TP53 p.R337H is highly prevalent in the south and southeast of Brazil and predisposes to ACT with low penetrance. Thus, we aimed to investigate whether genetic variants exist which are associated with an increased risk of developing ACT in TP53 p.R337H carrier children. Methods: A genetic association study was conducted in trios of children (14 girls, 7 boys) from southern Brazil carriers of TP53 p.R337H with (n = 18) or without (n = 3) ACT and their parents, one of whom also carries this pathogenic variant (discovery cohort). Results were confirmed in a validation cohort of TP53 p.R337H carriers with (n = 90; 68 girls, 22 boys) or without ACT (n = 302; 165 women, 137 men). Findings: We analysed genomic data from whole exome sequencing of blood DNA from the trios. Using deep learning algorithms, according to a model where the affected child inherits from the non-carrier parent variant(s) increasing the risk of developing ACT, we found a significantly enriched representation of non-coding variants in genes involved in the cyclic AMP (cAMP) pathway known to be involved in adrenocortical tumorigenesis. One among those variants (rs2278986 in the SCARB1 gene) was confirmed to be significantly enriched in the validation cohort of TP53 p.R337H carriers with ACT compared to carriers without ACT (OR 1.858; 95% CI 1.146, 3.042, p = 0.01). Interpretation: Profiling of the variant rs2278986 is a candidate for future confirmation and possible use as a tool for ACT risk stratification in TP53 p.R337H carriers. Funding: Centre National de la Recherche Scientifique (CNRS), Behring Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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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.

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Background: Uteroplacental insufficiency in fetuses with growth restriction (FGR) leads to chronic hypoxia and stress, predominantly affecting the adrenal glands. However, the mechanisms of impact remain unclear. Objectives: This study is aimed at comparing the Doppler indices of the adrenal artery and the adrenal gland sizes between FGR and those with normal growth. Materials and Methods: A multicenter, cross-sectional study was conducted from February to December 2023. We compared 34 FGR to 34 with normal growth in terms of inferior adrenal artery (IAA) Doppler indices and adrenal gland volumes. Results: The IAA peak systolic velocity (PSV) in the FGR group was 14.9 ± 2.9 cm/s compared to 13.5 ± 2.0 cm/s in the normal group, with a mean difference of 1.4 cm/s (95% confidence interval [CI]: 0.27-2.65; p value = 0.017). There were no significant differences between groups in terms of IAA pulsatility index (PI), resistance index (RI), or systolic/diastolic (S/D), with p values of 0.438, 0.441, and 0.658, respectively. The volumes of the corrected whole adrenal gland and the corrected neocortex were significantly larger in the FGR group, with p values of 0.031 and 0.020, respectively. Conclusion: Both increased IAA PSV and enlarged volumes of the corrected whole adrenal gland and neocortex were found in fetuses with FGR, suggesting significant adrenal gland adaptation in response to chronic intrauterine stress.

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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 adrenocorticotropic hormone (ACTH) levels. Stress-induced total plasma corticosterone levels were increased, while 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 (AR) knock-out animals, compared to wild-type litter mates. 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 AR activation affects CBG levels, in conjunction with effects on gene expression and HPA-axis reactivity.

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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.

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In humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/- rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active polyunsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregulated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.

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SUMMARY: Aging is an inevitable biological process that affects the function of all organs, including the adrenal gland, which is essential for producing steroid hormones that regulate metabolism, stress response, and immune activation. Understanding how aging affects the morphology of this gland is crucial to developing interventions to mitigate its adverse effects. Thus, this study aimed to describe the morphoquantitative alterations of the adrenal gland in senescent Sprague Dawley rats compared to adult rats. Twelve male rats were divided into 6 adult rats aged 6 months (group A) and 6 senescent rats aged 36 months (group S). Histopathological studies, quantification of collagen fibers types I and III, and stereological analysis were performed to determine the volume density (Vv), surface area (Sv), and number (Nv) of the nuclei of the zona fasciculata cells. Adrenal gland tissue from group S presented dysplasia, metaplasia, intracellular fat accumulation, fibrosis, blood vessel dilation, and increased presence of apoptotic cells. Capsule thickening and increased collagen type I were also observed. There was a significant decrease in Vv, Sv, and Nv of zona fasciculata nuclei in group S compared to group A. The results indicate that aging induces significant morphoquantitative changes in the adrenal gland, which could contribute to the decrease in glucocorticoid production and alterations in aldosterone and cortisol secretion observed in senescence. Understanding these alterations is crucial to developing interventions that mitigate the adverse effects of aging on the endocrine system.

El envejecimiento es un proceso biológico inevitable que afecta la función de todos los órganos, incluida la glándula suprarrenal, fundamental para la producción de hormonas esteroides que regulan el metabolismo, la respuesta al estrés y la activación inmunológica. Comprender cómo el envejecimiento afecta la morfología de esta glándula es crucial para desarrollar intervenciones que mitiguen sus efectos adversos. Así, el objetivo de este estudio fue describir las alteraciones morfocuantitativas de la glándula suprarrenal en ratas Sprague Dawley senescentes comparadas con ratas adultas. Se utilizaron 12 ratas macho, divididas en dos grupos: 6 ratas adultas de 6 meses de edad (grupo A) y 6 ratas senescentes de 36 meses de edad (grupo S). Se realizaron estudios histopatológicos, cuantificación de fibras de colágeno tipos I y III y análisis estereológicos para determinar la densidad de volumen (Vv), de superficie (Sv) y de número (Nv) de los núcleos de las células de la zona fasciculada. El tejido de la glándula suprarrenal del grupo S presentó displasia, metaplasia, acumulación de grasa intracelular, fibrosis, dilatación de vasos sanguíneos y mayor presencia de células apoptósicas. También se observó un engrosamiento de la cápsula y un incremento del colágeno tipo I. Hubo una disminución significativa en Vv, Sv y Nv de los núcleos de la zona fasciculada en el grupo S en comparación con el grupo A. Los resultados indican que el envejecimiento induce cambios morfocuantitativos significativos en la glándula suprarrenal, lo que podría contribuir a la disminución en la producción de glucocorticoides y alteraciones en la secreción de aldosterona y cortisol observadas en la senescencia. Comprender estas alteraciones es crucial para desarrollar intervenciones que mitiguen los efectos adversos del envejecimiento en el sistema endocrino.

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Small-cell melanoma masquerading as an adrenal non-Hodgkin lymphoma. The index report illustrates the deceptive cytomorphologic features of a small cell type malignant melanoma metastatic to the adrenal gland. The diagnosis was confirmed by performing immunocytochemistry on the cell block sections. The key cytomorphologic mimics and their distinctive features have also been highlighted.

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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.

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Background: Functional adrenal tumors may contribute to poor hypertension control and electrolyte abnormalities, thus increasing the risk of cardiovascular mortality. Currently, laparoscopic adrenalectomy is an effective surgical option that contributes to improved treatment outcomes as compared to open surgery. The purpose of this study was to evaluate the outcomes of laparoscopic adrenalectomy performed by a general surgeon at a low-volume center and to identify clinicopathological risk factors for postoperative persistent hypertension. Methods: A retrospective study of patients with functional adrenal tumors who underwent laparoscopic adrenalectomy at Srinakharinwirot University, Thailand, between 2014 and 2022. Clinicopathologic and postoperative data were examined. Results: This study included twenty-five patients; the indications for laparoscopic adrenalectomy included primary aldosteronism in 19 (76%), pheochromocytoma in 4 (16%), and Cushing's syndrome in 2 (8%). The average time of surgery was 103.5 ± 19.7 min, and intraoperative complications occurred in three patients (12%), with one patient requiring conversion to open surgery (4%). The postoperative systolic (125 ± 15 vs. 158 ± 18 mmHg; p < 0.001) and diastolic (78.5 ± 6.7 vs. 95.3 ± 10 mmHg; p = 0.013) blood pressure significantly decreased compared to prior surgery, but only 19 patients (76%) achieved a cure for hypertension. Multivariate analysis revealed that the patient's physical status, as classified by the American Society of Anesthesiologists (odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.43-1.32, p = 0.001), and the need for at least three antihypertensive medicines (OR = 0.7, 95% CI 0.36-1.2, p = 0.002), were independent predictive factors of persistent hypertension after surgery. Conclusion: Laparoscopic adrenalectomy is a safe and effective surgical treatment for functional adrenal tumors, even when performed in a low-volume center. According to the American Society of Anesthesiologists' physical categorization, the patient's physical condition and the necessity for at least three antihypertensive medications are predictors of postoperative hypertension. Trial registration: The study was registered with the Thai Clinical Registry Trials: TCTR20230707007.

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To describe a rare case of left adrenal Castleman disease (CD), splenomegaly, and cirrhosis. An examination revealed a left adrenal mass for more than three months, the patient, 44, was well-prepared for surgery after her left adrenal tumor was removed laparoscopically using a retroperitoneal approach, her postoperative pathology suggested that she had Castleman disease of the adrenal glands, and there had been no metastasis or recurrence during the six-month follow-up period. We have evaluated linked literature reports in this article, reporting relevant clinical knowledge regarding the disease and synthesizing previous research, in an effort to increase our understanding of it.

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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.

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Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.

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Background: Epithelioid angiomyolipoma (EAML), a subtype of angiomyolipoma, is distinct. It has a biologic behavior of borderline tumor, a malignant tendency, and a risk of metastasis and recurrence. Adrenal EAML is very rare. It is true that only six cases of adrenal EAML have been documented in the English-language literature. Case Description: A 65-year-old man who underwent a laparoscopic left adrenalectomy in July 2022 has adrenal EAML and this is a case report about it. The mass was surrounded by abundant blood vessels and adherence with surround-tissue. Postoperative pathology of the tumor analysis revealed adrenal epithelioid vascular smooth muscle lipoma. The patient underwent left upper abdomen and lumbar pain in July 2022. The enhanced computed tomography (CT) scan of the abdomen showed markedly enhanced masses in and around the left adrenal gland. A second left laparoscopic adrenalectomy was performed under general anesthesia. Postoperative pathology showed two taupe nodules of left adrenal, maximum diameter 0.9 to 1.1 cm. The postoperative pathological diagnosis in combination with immunohistochemistry was EAML. The patient was discharged 10 days later with symptomatic treatment with low molecular heparin. Conclusions: Adrenal EAML has a biologic behavior of borderline tumor with malignant potential and a risk of distant metastasis and recurrence. Therefore, radical surgical resection should be considered as its necessary treatment. Long-term postoperative follow-up is an important part of the treatment.

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The extracellular matrix (ECM) comprises macromolecules that shape a complex three-dimensional network. Filling the intercellular space and playing a crucial role in the structure and function of tissues, ECM regulates essential cellular processes such as adhesion, differentiation, and cell signaling. In the human adrenal gland, composed of cortex and medulla surrounded by a capsule, the ECM has not yet been directly described, although its impact on the processes of proliferation and steroidogenesis of the adrenal cortex is recognized. This study analyzes the ECM of the adult human adrenal cortex, which was separated into outer fraction (OF) and inner fraction (IF), by comparing their proteomic profiles. The study discusses the composition, spatial distribution, and relevance of differentially expressed ECM signatures of the adrenal cortex matrisome on adrenal structure and function. The findings were validated through database analysis (cross-validation), histochemical, and immunohistochemical approaches. A total of 121 ECM proteins were identified and categorized into glycoproteins, collagens, ECM regulators, proteoglycans, ECM-affiliated proteins, and secreted factors. Thirty-one ECM proteins were identified only in OF, nine only in IF, and 81 were identified in common with both fractions. Additionally, 106 ECM proteins were reported in the Human matrisome DB 2.0, and the proteins differentially expressed in OF and IF, were identified. This study provides significant insights into the composition and regulation of the ECM in the human adrenal cortex, shedding light on the adrenal microenvironment and its role in the functioning, maintenance, and renewal of the adrenal gland.