Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3ß-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.

Ultrasonographic and pathological features of primary adrenal lymphoma.

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Acute spontaneous non-hemorrhagic adrenal infarction with systemic lupus erythematosus and antiphospholipid antibody syndrome: A case report.

RATIONALE: Adrenal infarction (AI) is a rare type of adrenal damage, which is relatively common in systemic lupus erythematosus, antiphospholipid antibody syndrome (APS) and pregnancy. The diagnosis of AI is mainly by computed tomography (CT) and magnetic resonance imaging, but is easily confused with other adrenal disease. Hence, this report details a condition of AI with systemic lupus erythematosus, APS and made a differential diagnosis from imaging. PATIENT CONCERNS: We report a case of a 55-year-old woman with pain in her fossa axillaries and inguinal regions. Then CT scan disclosed bilateral adrenal diseases, and the patient was diagnosed with systemic lupus erythematosus, APS and AI after additional autoimmune examinations. DIAGNOSES: The patient was diagnosed as systemic lupus erythematosus with lupus nephritis, hematological damage and oromeningitis, APS, AI and secondary blood coagulation disorders. INTERVENTIONS: The patient was treated with methylprednisolone, hydroxychloroquine and low molecular heparin. OUTCOMES: The patient relieves and remains well 1 year after treatment. LESSONS SUBSECTIONS: AI can be divided hemorrhagic and non-hemorrhagic, with bilateral lesions more common. In our case, the AI was bilateral, partially involved and non-hemorrhagic, and the "cutoff sign" was first put forward in CT, which might assist the diagnosis.

Gastroprotective Effect of GABA in Metabolic Stress.

We studied the effect of enteral administration of GABA on the gastric mucosa in male Wistar rats (n=47) with modeled metabolic stress (food deprivation for 9 days with free access to water). The relative weights of the adrenal glands and thymus were determined, and histological examination of the stomach was performed. In control rats, modeling the metabolic stress was accompanied by the development of erosive damage to the gastric mucosa related to blood supply disturbances. Administration of GABA prevented erosions and exhibited a pronounced gastroprotective effect. Thus, administration of GABA can be a promising method for the prevention and treatment of erosive gastric lesions associated with metabolic stress.

Dielectric characterisation of human adrenal glands and adrenal tumours for the development of microwave ablation technologies for hypertension treatment.

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

Adrenal gland injury in trauma patients and its impact on clinical outcomes.

BACKGROUND: Adrenal gland injury (AGI) associated with trauma is an uncommon and often overlooked condition. This study aimed to evaluate the frequency of AGI in individuals with severe trauma injuries and investigate the outcomes of patients with AGI. METHODS: All patients admitted to a tertiary trauma referral center under the trauma protocol who had a computed tomography (CT) scan between January 2012 and January 2023 were analyzed retrospectively. Patients who were dead on arrival and patients with incomplete data were excluded. They were classified into two main groups, adult and pediatric, and further subcategorized by the presence or absence of radiologically evident AGI. Demographic data, mechanism of injury, injury severity scores (ISS), presence of concurrent abdominal injury, and 30-day mortality rates were compared. A separate analysis was performed for factors affecting mortality rates. RESULTS: A total of 1,253 patients were included: 950 adults and 303 pediatric patients. In the adult group, AGI was detected in 45 (4.7%) patients and was more commonly associated with the following mechanisms of injury: motor vehicle accidents (26.7% vs. 14.3%) and pedestrian accidents (37.8% vs. 15.5%). Injury to the right side was more common (55.6%). Patients with AGI had higher rates of concurrent liver (17.8% vs. 3.9%), spleen (11.1% vs. 3.6%), and kidney injuries (15.6% vs. 1.3%). In the pediatric population, AGI was detected in 30 patients (14.8%), a significantly higher rate compared to the adult group. Similar to the adult group, AGI was more commonly associated with concurrent abdominal injuries and had a right-sided dominance (60%), but the rate of concurrent abdominal injuries was higher in the pediatric group (80% vs. 46%). The 30-day mortality was significantly higher in both adult and pediatric AGI groups compared to patients without AGI (adult: 15.6% vs. 2.9%, pediatric: 10% vs. 1.8%). In patients with AGI, major head and neck injuries and chest injuries were associated with mortality. CONCLUSION: Adrenal gland injuries due to trauma are not uncommon. They are usually associated with blunt trauma and other concurrent abdominal organ injuries. The major contributors to mortality in patients with AGI were major head and neck injuries and chest injuries.

Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess and KDM1A inactivation.

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.

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

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 3ß-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.

Impact of Aging on the Morphology of the Adrenal Gland in Rats / Impacto del Envejecimiento en la Morfología de la Glándula Suprarrenal en Ratas

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.

Super Mario sign at somatostatin receptor PET/CT.

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We present the case of a 59-year-old male with well differentiated gastric neuroendocrine tumour (grade II) treated with surgery. 68Ga-DOTA NOC PET/CT was performed to rule out metastasis. 68Ga-DOTA NOC showed physiological uptake in the bilateral adrenal and horseshoe kidney appearing as the famous character Super Mario. There is no evidence of any abnormal somatostatin avid lesion.

Metastatic diseases to the adrenal gland: A comprehensive study from an academic institution with emphasis on clinical occult cases.

The adrenal gland is one of the common sites of metastasis and distinguishing metastatic diseases from adrenal primary neoplasms is essential for accurate clinical management of patients. Our study aimed to elucidate the spectrum and clinicopathologic features of metastatic solid tumors to the adrenal gland at an academic institution, with special focus patients presented with solitary adrenal masses without previously known malignancies. Our departmental database (2013-2022) was retrospectively searched and 129 patients with metastatic solid tumors involving the adrenal gland were identified. The median age at the initial diagnosis of metastatic diseases was 64 years old (range, 54-70 years). The majority of the diseases were presented as unilateral (n=118) or unifocal (n=119) involvement. Most patients had known prior or concurrent malignancies (n=125), whereas adrenal gland involvement was the initial clinical presentation in 4 patients. The most common primary carcinomas included renal cell carcinoma (n=84), lung adenocarcinoma (n=21), urothelial carcinoma (n=3) and hepatocellular carcinoma (n=3). In 104 (80 %) patients with available follow up (median of 39 months, ranging 0-81 months), 43 patients died of disease. Metastatic diseases are usually exercised in the differential diagnosis when there is clinically known malignant primary. In patients without clinical known malignancies, close clinical and radiologic correlation and thorough relevant clinical work up are critical, because clinical occult malignancy may metastasize to the adrenal gland as a solitary mass at the initial presentation, although it is rare.

Robotic Left Pancreatectomy with Perirenal Tissue Excision and Left Adrenalectomy (Posterior Ramps) for Pancreatic Ductal Adenocarcinoma Abutting the Adrenal Gland.

BACKGROUND: Radical antegrade modular pancreato-splenectomy (RAMPS) has been largely described in left-sided pancreatic cancers.1.J Hepato-Biliary-Pancreat Sci 29:1156-1165 Its prognostic advantage is not clear, although a theoretical improvement in R0 resection rate has been shown.2.J Am Coll Surg 204:244-249 Furthermore, RAMPS is usually carried out without adrenal gland removal, the so-called anterior RAMPS, while extending the resection to the adrenal plane could impair perioperative outcomes.3.HPB 25:311-319 METHODS: A 40 mm pancreatic ductal adenocarcinoma (PDAC) was found in a 70-year-old patient. Tumor infiltrates the adrenal gland and a robotic posterior RAMPS was indicated. RESULTS: After sectioning the splenic vessels and the pancreatic neck, the dissection was directed vertically in a sagittal plane along the left border of the superior mesenteric artery to identify the left renal vein. Our dissection plane was then directed on a caudo-cranial axis, after identification of the left renal artery and below the adrenal gland. The resection was also delimitated medially by the left borders of the superior mesenteric artery and the aorta, and posteriorly by the renal parenchyma. Postoperative course was marked by a biochemical leak. The patient was discharged on postoperative day (POD) 5 and the drain removed at POD 18. Pathological examination confirmed a pT2N2 PDAC with negative margins, with 4/18 positive nodes. CONCLUSIONS: The robotic platform is routinely employed in pancreatic surgery. Thanks to its increased degree of movement, its dexterity, and the magnification, this approach can help surgeons with vascular identification and control, in performing extended lymphadenectomies, and finding the correct planes of dissection. All these elements are crucial in a well-performed posterior RAMPS.

MRI-based adrenal gland volume is associated with cardiovascular alterations in individuals without prior cardiovascular disease.

Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic-pituitary-adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI. Manual segmentation of adrenal glands was performed on VIBE-Dixon gradient-echo sequence. MRI based evaluation of cardiac parameters was achieved semi-automatically. Cardiometabolic risk factors were obtained through standardized interviews and medical examination. Univariate and multivariate associations were derived. Bi-directional causal mediation analysis was performed. 351 participants were eligible for analysis (56 ± 9.1 years, male 58.7%). In multivariate analysis, significant associations were observed between adrenal gland volume and hypertension (outcome hypertension: Odds Ratio = 1.11, 95% CI [1.01, 1.21], p = 0.028), left ventricular remodelling index (LVRI) (outcome LVRI: ß = 0.01, 95% CI [0.00, 0.02], p = 0.011), and left ventricular (LV) wall thickness (outcome LV wall thickness: ß = 0.06, 95% CI [0.02, 0.09], p = 0.005). In bi-directional causal mediation analysis adrenal gland volume had a borderline significant mediating effect on the association between hypertension and LVRI (p = 0.052) as well as wall thickness (p = 0.054). MRI-based assessment of adrenal gland enlargement is associated with hypertension and LV remodelling. Adrenal gland volume may serve as an indirect cardiovascular imaging biomarker.

Beyond symptomatology: A comparative analysis of unilateral and bilateral macronodular mild autonomous cortisol secretion.

OBJECTIVE: To investigate the clinical, laboratory findings and signal intensity index (SII) on magnetic resonance imaging (MRI) of patients with bilateral and unilateral macronodular mild autonomous cortisol secretion (MACS). PATIENTS AND MEASUREMENTS: Clinical and laboratory findings of 81 patients with MACS were examined from retrospective records. SII of adenomas and internodular areas were evaluated by MRI. The unilateral group included patients with an adrenal macronodule (≥1 cm) in a single adrenal gland, while the bilateral group included patients with at least one macronodule in both adrenal glands. RESULTS: In total, 46 patients were in the unilateral (57%), while 35 (43%) patients were in the bilateral groups. The dehydroepiandrosterone sulphate (DHEA-S) level was lower in the unilateral than in the bilateral group (p < .001). The presence of type 2 diabetes mellitus (T2DM), glycosylated haemoglobin (HbA1c) and low-density lipoprotein (LDL) concentrations were higher in the bilateral group (p < .05). However, no significant difference was detected in terms of adrenocorticotropic hormone (ACTH) and overnight 1 mg dexamethasone suppression test (DST) between the two groups (p > .05). There was no difference in SII between adenomas within the same patient, as well as between the unilateral and bilateral groups (p > .05). Logistic regression analysis based on the differentiation between unilateral and bilateral macronodular MACS demonstrated that DHEA-S, HbA1c and LDL concentrations were associated factors. CONCLUSION: DHEA-S levels may not be as suppressed in patients with bilateral macronodular MACS as compared to those with unilateral adenoma. T2DM and hypercholesterolaemia have a higher frequency in bilateral patients. However, ACTH, overnight 1 mg DST and SII may not provide additional information for differentiation of bilaterality and unilaterality.

Primary diffuse large B-cell lymphoma of adrenal gland: A case report.

INTRODUCTION: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis. CASE REPORT: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma. CONCLUSION: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.

Evaluation of adrenal vein anatomy by adrenal venous sampling in patients with primary aldosteronism in Chinese.

Accurate cannulation of the adrenal vein is challenging during adrenal venous sampling (AVS) because of the variations in adrenal vein anatomy. This study aimed to investigate the adrenal venous morphology in Chinese and improve the success rate of AVS. A total of 221 participants with primary aldosteronism (PA) who underwent AVS were enrolled. Compare the morphology among subgroups divided according to sex, body mass index (BMI), and with or without adenoma. The success rate of right, left, and bilateral AVS was 98.60%, 97.20%, and 96.85%, respectively. The triangular pattern was the most common (39.37%) on the right side, while the glandlike pattern (70.14%) on the left. The proportion of adrenal venous morphology varies among patients with different sexes (χ2 = 21.335, P < .001), BMI (χ2 = 10.642 P = .031), and with or without adenoma (χ2 = 10.637, P = .031) on the right side, and the male, obese and adenoma group showed a higher proportion of glandlike pattern than triangular pattern. If only dependent on computed tomography, 9.05% of patients incorrectly diagnose the dominant side, 14.48% of patients would have inappropriate surgery meanwhile 25.34% of patients would miss the surgical opportunity. In conclusion, the most common types of right and left adrenal venous morphology were triangular pattern and glandlike pattern, respectively. Sex, BMI, and the presence of adenoma affected right adrenal venous morphology. Adequate knowledge of the adrenal venous morphology is critical for improving the success rate of AVS and making an appropriate treatment for PA.

Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.

Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.

The Role of the Gap Junction Protein Connexin in Adrenal Gland Tumorigenesis.

Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.

A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia-CYP21A2-R484Q Mutant Mouse.

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2, causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.