Adrenal Tissue Research Articles

Fine construction of gene coexpression network analysis using GTOM and RECODE detected a critical module of neuroblastoma stages 4 and 4S.

Stage 4 neuroblastoma (NBL), a solid tumor of childhood, has a poor prognosis. Despite intensive molecular genetic studies, no targetable gene abnormalities have been identified. Stage 4S NBL has a characteristic of spontaneous regression, and elucidation of the mechanistic differences between stages 4 and 4S may improve treatment. Conventional NBL studies have mainly focused on the detection of abnormalities in individual genes and have rarely examined abnormalities in gene networks. While the gene coexpression network is expected to contribute to the detection of network abnormalities, the fragility of the network due to data noise and the extraction of arbitrary topological structures for the high-dimensional network are issues. The present paper concerns the classification method of stages 4 and 4S NBL patients using highly accurate gene coexpression network analysis based on RNA-sequencing data of transcription factors (TFs). In particular, after applying a noise reduction method RECODE, generalized topological overlapping measure (GTOM), which weighs the connections of nodes in the network structure, succeeded in extracting a cluster of TFs that showed high classification performance for stages 4 and 4S. In addition, we investigated how these clusters correspond to clinical information and to TFs which control the normal adrenal tissue and NBL characters. A clustering method is presented for finding intermediate-scale clusters of TFs that give considerable separation performance for distinguishing between stages 4 and 4S. It is suggested that this method is useful as a way to extract factors that contribute to the separation of groups from multiple pieces of information such as gene expression levels.

Unveiling three accessory spleens in one patient: a rare case report and literature review.

During embryogenesis, the spleen undergoes intricate developmental processes, originating from mesenchymal cells in the dorsal mesentery. An accessory spleen, a common anomaly found in autopsies and abdominal CT scans, can often be mistaken for different types of tumors. To the best of our knowledge, this is the first case in Syria documenting the occurrence of 3 accessory spleens in a patient who had previously undergone splenectomy. A 33-year-old male presented with right hypochondrium pain, sharp and radiating to the right flank, exacerbated by movement and large meals. Past medical history included mild Irritable Bowel Syndrome (IBS) and splenectomy due to a traumatic accident in childhood. On admission, vital signs were stable, with abdominal tenderness in the right upper quadrant. Laboratory investigations showed normal values. Ultrasound revealed a lobulated mass at the right adrenal gland (4.5 × 5cm) with an isoechoic to hypoechoic texture. Multi-slice computed tomography (MSCT) Scan showed multiple nodules in the right adrenal gland, regular in shape, exerting a compressive mass effect, and significant lymphadenopathy around the abdominal aorta. Elevated metanephrine levels raised suspicion of an extra-adrenal pheochromocytoma. Laparoscopic surgery was performed, revealing accessory spleens and normal adrenal tissue with no malignancy. Healthcare providers should consider accessory spleens as a differential diagnosis for masses near the adrenal glands. Multiple accessory spleens in the adrenal region can complicate cases. Accessory spleens in uncommon locations like the adrenal glands can be challenging to diagnose and manage.

Preoperative Epidural Infusion for Blood Pressure Control in Phaeochromocytoma

The 2004 World Health Organization (WHO) classification of endocrine tumours defines phaeochromocytoma as a catecholamine-producing intra-adrenal tumour arising from the chromaffin cells. The most important functional characteristics of the adrenal and extra-adrenal sympathetic tissue derived tumours is the production of various types of catecholamines and the related clinical attributes [1]. Preoperative blood pressure control in phaeochromocytoma is an uphill task using multiple medications leading to post operative hypotension. It is well known that complete prevention of perioperative hypertension and tachycardia cannot be achieved by any dose or combination of drugs. Epidural anesthesia is often used for pain control in open resection of these tumours; one of its side effects is hypotension [2]. We describe here a case of phaeochromocytoma in whom perioperative blood pressure control was achieved with the help of epidural drugs instead of systemic antihypertensive medications.

Somatic GNAQ, CTNNB1, and CACNA1C Mutations in Cat Aldosterone-Secreting Tumors.

Primary aldosteronism (PA) is a common cause of human hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 are found in at least 80% of aldosterone-producing adenomas, which cause unilateral PA in humans. Somatic mutations have been identified infrequently in 7 other genes; few of these were known to play a role in aldosterone secretion before the discovery of their mutations. Interrogating somatic mutations in the domestic cat, in which spontaneous PA is also known to occur, might improve the understanding of normal adrenal gland physiology and the pathophysiology of PA. DNA and RNA extracted from tissue from 13 cats with unilateral aldosterone-secreting tumors, including 8 carcinomas and 5 adenomas, underwent whole genome sequencing, targeted Sanger sequencing, and RNA sequencing. Single-nucleotide substitution variants were filtered to select those with a predicted deleterious effect on protein function and a suspected role in aldosterone secretion. Probable functional somatic single-nucleotide polymorphisms (n=8) were found in 3 adenomas and 2 carcinomas. Mutations with predicted significant effects were identified in 2 genes also mutated in human PA; GNAQ and CTNNB1, and in a residue of CACNA1C analogous to a common CACNA1D mutation. In contrast to humans, CACNA1C expression was much greater than CACNA1D in both feline tumor and nontumor adrenal tissue. No mutations were identified in KCNJ5, CACNA1D, ATP1A1, or ATP2B3. Similar mutations were identified in cats to those found in humans. It is, therefore, likely that both species have shared underlying selection pressures for mutations that increase aldosterone secretion.

A Frozen Tale of Two Tumors in the Pancreas: An Intraoperative Diagnostic Challenge of Clear Cell Pancreatic Neuroendocrine Tumor Mimicking Metastatic Clear Cell Renal Cell Carcinoma

Abstract Introduction/Objective Clear cell pancreatic neuroendocrine tumor (PanNET) is rare, with very few cases reported in the literature, and is often found in patients with von Hippel-Lindau (VHL) disease. The differential for this entity includes ectopic adrenal tissue and metastatic clear cell neoplasms. These challenges during intraoperative consultation add to the complexity of diagnosing this condition. Distinguishing it from other pancreatic lesions requires careful examination and further ancillary testing. Methods/Case Report We report a case of clear cell PanNET mimicking metastatic clear cell renal cell carcinoma (RCC) in a 56-year-old woman with recently diagnosed VHL. She presented with renal masses and a pancreatic lesion with previous biopsy showing conventional NET. Intraoperative consultation during her pancreaticoduodenectomy identified a 1.3 cm well-circumscribed, golden-yellow solid mass. Further characterization was deferred to permanent sections given the diagnostic challenge of distinguishing between a PanNET and metastatic clear cell RCC. Permanent sections showed nests of clear cells with prominent nucleoli. The neoplastic cells were immunohistochemically positive for neuroendocrine markers synaptophysin, chromogranin and insulinoma- associated protein 1(INSM1), as well as pankeratin and PAX8, with a Ki-67% proliferation index <1%, consistent with low-grade clear cell PanNET. Clear cell RCC marker, CA-IX, as well as adrenocortical marker SF1, were negative. The combination of immunohistochemical stains is key for making the diagnosis. The previously biopsied conventional PanNET was also identified, which was positive for neuroendocrine markers and had a Ki-67 proliferation index <1%. Results (if a Case Study enter NA) NA Conclusion Given the rarity of this entity and its strong association with VHL, clear cell PanNET should be considered in the intraoperative consultation to inform clinical management. Furthermore, literature review indicates that metastatic RCC in the pancreas is exceptionally rare in VHL patients and typically of low nuclear grade, suggesting low metastatic potential. Thus, this case emphasizes the diagnostic challenges and the necessity of deferring to permanent sections with immunohistochemical work-up during intraoperative consultation or when assessing small biopsies.

Immunohistochemical expression of CYP11A1, CYP11B, CYP17, and HSD3B2 in functional and nonfunctional canine adrenocortical tumors.

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.

6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma

Abstract Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None. Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (<0.02 miu/ml), low FSH (<0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and <5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or >7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management. Presentation: 6/3/2024

Prenatal and Pregnancy Management of Congenital Adrenal Hyperplasia.

Management of patients with congenital adrenal hyperplasia (CAH) poses challenges during pregnancy and prenatal stages, impacting fertility differently in men and women. Women with CAH experience menstrual irregularities due to androgen and glucocorticoid precursor interference with endometrial development and ovulation. Genital surgeries for virilization and urogenital anomalies further impact fertility and sexual function, leading to reduced heterosexual relationships among affected women. Fertility rates vary, with a lower prevalence of motherhood, primarily among those with classic CAH, necessitating optimized hormonal therapy for conception. Monitoring optimal disease control during pregnancy poses challenges due to hormonal fluctuations. Men with CAH often experience hypogonadotrophic hypogonadism and complications like testicular adrenal rest tissue, impacting fertility. Regular monitoring and intensified glucocorticoid therapy may restore spermatogenesis. Genetic counselling is vital to comprehend transmission risks and prenatal implications. Prenatal dexamethasone treatment in affected female fetuses prevents virilization but raises ethical and safety concerns, necessitating careful consideration and further research. The international "PREDICT" study aims to establish safer and more effective prenatal therapy in CAH, evaluating dosage, safety, and long-term effects.

ЭНДОТЕЛИН-1 В КОРТИКОЦИТАХ НАДПОЧЕЧНИКОВ ПРИ СОЧЕТАНИИ ЧЕРЕПНО-МОЗГОВОЙ ТРАВМЫ И ЭНДОТОКСЕМИИ

Neuroinflammation in traumatic brain injury (TBI) and endotoxemia caused by bacterial lipopolysaccharide have an indirect effect through blood vessels on paracrine and autocrine processes regulating steroidogenesis of adrenal corticocytes. The vasoconstrictor peptide endothelin-1 plays a key role in blood vessel homeostasis. This protein, as a regulator, may be involved in the integration of the listed mechanisms of action on the adrenal glands during endotoxemia and inflammation. Purpose of the study: immunohistochemical characterization of the localization sites and content of endothelin-1 in adrenal corticocytes during a combination of TBI and endotoxemia in the experiment. Materials and methods. Moderate TBI was reproduced in mature rats using a falling weight model weighing 200 g, endotoxemia was induced by intraperitoneal administration of pyrogenal at a total dose of 100 μg/kg body weight. Endothelin-1 was detected in adrenal tissues using the immunohistochemical method and morphometric analysis of the images was performed. Results. In all experimental groups, the stability of the morphometric characteristics of the ratio of the calving cortex and the adrenal medulla was found. With the combination of TBI and endotoxemia, there is a decrease in the area of the nucleus and cytoplasm of adrenal corticocytes and, as a consequence, the nuclear-cytoplasmic ratio. A morphological study revealed an increase in the content of endothelin-1 in the cells of the adrenal cortex, while in the adrenocytes of the medulla, a significant positive reaction to the presence of the peptide was not detected. Conclusion. The results obtained demonstrate that the combination of TBI and endotoxemia causes dysfunction of adrenal cortex cells with an increase in the synthesis of endothelin-1 in them.

Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia - a longitudinal analysis over 10 years

Abstract Background Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function. Methods Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue (TART)); median observation period 12 years; testosterone (T), 11-oxygenated androgens, gonadotropins and inhibin B measurement at each timepoint. Results T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for BMI, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/l) than those without (11.9 ± 0.71 nmol/l). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/l vs. 10.3 ± 1.0 to 12.8± 1.9 nmol/l); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1± 3.2 to 35.1 ± 1.8 mg/d; vs. no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable. Conclusion T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.

Remodeling of the structural components of the capsule and glomerular zone of the adrenal glands cortex of white rats under the influence of a complex of food additives at the late terms of the experimental study

With food additives, we can add flavour to food, extend its shelf life, and make it look good. However, even small amounts of these additives can lead to diseases of various organs and systems. The aim of our work is to establish metrics and morphological changes in the structure of the capsule and the glomerular zone of the cortex of the adrenal glands of rats at the later stages of the experimental study under the conditions of consumption of a complex of food additives: monosodium glutamate, sodium nitrite and Ponceau 4R. The control group of rats consumed oral drinking water and saline. The rats of the experimental groups were orally administered once a day with a 10 % solution of sodium nitrite (E250), sodium glutamate (E621) or Ponceau 4R. The dosages of food additives were two times lower than the permissible norm in food. The rats were withdrawn from the experiment after 8, 12 and 16 weeks. The adrenal glands were removed for the study. Paraffin sections were stained with hematoxylin and eosin, and semi-thin sections with toluidine blue, and examined using a light microscope Biorex with a digital microphoto attachment DSM 900. Ultrathin sections were examined in a TEM-125 K electron microscope. For morphometric analysis, the structure of the capsule and the glomerular zone of the cortex of the adrenal glands of rats at the later stages of the experimental study was studied. The study results were analysed using the software package “InStat”. At the late stages of the experimental study, the adrenal capsule underwent irreversible changes. The average thickness of the adrenal connective tissue capsule decreased by the end of the 16th week of the experimental research. Similarly, the average thickness of the cortex decreased with each subsequent week relative to the control values, indicating significant structural and functional disorders. The average thickness of the glomerular zone of the adrenal cortex periodically changed as a compensatory reaction in response to the administration of a complex of food additives to rats. The phenomena of nucleus pyknosis and sludge syndrome were detected, which indicated compensatory and adaptive processes at the microscopic level. The analysis of electron micrographs revealed destroyed granular endoplasmic reticulum cisternae and mitochondrial remnants. Thus, it has been established that using a complex of food additives (monosodium glutamate, sodium nitrite and Ponceau 4R) directly affects the adrenal glands of rats. This effect causes structural changes in the cortex and medulla, causing alteration and hypertrophy of cells in these areas. Additionally, hyperhydration of the connective tissue stroma and compensatory-restorative reactions aimed at transcription factors and internal mechanisms of nitric oxide formation were recorded.

131I]6ß-Iodomethyl-19-norcholesterol SPECT/CT for the Lateralization of Mineralocorticoid Overproduction in Primary Aldosteronism.

In 42 consecutive patients with confirmed primary aldosteronism, molecular imaging has been performed. After dexamethasone suppression of the non-affected adrenal tissue, 37 MBq [131I]6ß-iodomethyl-19-norcholesterol was injected i.v., and SPECT/CT images were taken 7 days later. Based on the visual evaluation of the images by two nuclear medicine specialists, patients with one-sided tracer accumulation underwent adrenalectomy. To identify a SPECT/CT parameter that best characterizes the side difference, the maximum counts and the mean counts of spherical VOIs were analyzed. Of the 42 patients, 24 had one-sided aldosterone overproduction by SPECT/CT. After surgical removal of the involved adrenal, all 24 patients with SPECT/CT-identified unilateral aldosteronism achieved biochemical cure, defined as a normalized potassium level combined with an aldosterone-to-renin ratio ≤ 30. To identify the best measurable parameter of SPECT/CT side difference, the mean counts and maximum counts of a series of spherical VOIs of different diameters were analyzed. The ratio of the mean counts of 3 cm spherical VOIs of the right and left adrenal regions (lateralization index) was the best discriminator; a ratio of ≥1.29 was characteristic of one-sided disease, without overlap between the one-sided and two-sided patient groups. [131I]6ß-iodomethyl-19-norcholesterol SPECT/CT with a count-based image interpretation and side-ratio calculation may be an equipollent non-invasive substitute for adrenal venous sampling in the lateralization of mineralocorticoid overproduction. It reliably identifies unilateral disease and facilitates patients' selection for surgical intervention. If confirmed by others, this functional imaging may replace AVS when lateralization is required for management decisions in primary aldosteronism.

Abstract P147: Inappropriate Activation of the Leptin-Aldosterone-Endothelial Mineralocorticoid Receptor Axis Promotes Salt Sensitivity of Blood Pressure in Young Female Mice

While compelling clinical evidence indicates that women are more salt-sensitive than men, the mechanisms of the onset of women’s salt-sensitive blood pressure (SSBP) remain largely elusive. Herein, we employed salt-sensitive (SS)-Balb/C and salt-resistant (SR)-C57Bl/6 mice to investigate the etiopathology of SSBP in females. We hypothesized that a high-salt diet alters the leptin-aldosterone-endothelial mineralocorticoid receptor axis (ECMR), leading to SSBP and vascular dysfunction in young SS-female mice. Eleven-week-old female mice were fed a normal (0.4%, NSD) or a high salt diet (4%, HSD) for 7-days. We implanted radiotelemeters for BP monitoring at baseline, HSD, and in response to the leptin receptor (LepR) blockade combined with HSD. Following euthanasia, mesenteric arteries are isolated to measure vascular function via wire myography. HSD elevated mean arterial pressure in Balb/C (NSD: 98.4±2.3 vs. HSD: 105.1±0.9 mmHg) but not in C57 mice (NSD: 99.3±0.9 vs. HSD: 101.3±0.5 mmHg). However, SS-Balb/C mice showed superior natriuretic function in response to salt loading experiments (NSD: 13.3% vs. HSD: 42.3%) as opposed to C57 mice (NSD: 25.8% vs. HSD: 35.1%) (N=3). HSD feeding notably blunted endothelial relaxation to acetylcholine in Balb/c (NSD: 96.5% vs. HSD: 75.4%, N=7), an effect not seen in C57. SS-Balb/C mice failed to suppress aldosterone and adrenal aldosterone synthase (CYP11B2) levels (protein and transcript) compared to C57 mice. This concomitated a 1.8-fold increase in adrenal steroidogenic acute regulatory (StAR) mRNA in SS-Balb/C mice. HSD raised CYP11B2 protein levels in the visceral adipose tissue (VAT) of Balb/C mice. Leptin regulating CYP11B2 expression; we measured fat mass, leptin, and LepR expression. HSD enhanced fat accumulation (C57: +0.7% vs. Balb/c: +26.5%, N=12), leptin levels, and LepR transcript in the adrenal and VAT only in Balb/C mice. LepR blockade reduced BP in Balb/C mice fed a HSD (HSD: 105.1±0.9 vs. HSD+Allo-aca: 100.3±1.9 mmHg). HSD elevated ECMR expression only in Balb/C mice (N=6). To test the potential role of aldosterone-mediated ECMR activation in SSBP, we employed mice with selective overexpression of MR in endothelial cells (ECMR-OE). ECMR-OE young female mice exhibited impaired endothelial function (N=7), reproducing the effects of HSD. In conclusion, SSBP involves an over-activation of the leptin-aldosterone axis in both adrenal and adipose tissue, along with an escalated ECMR expression in females.

Abstract P208: Chromophobe Renal Cell Carcinoma Presenting as Hypertension in a Young Adult: A Case Report

Introduction: Renal cell carcinoma (RCC) is a recognized but rare cause of secondary hypertension. Hypertension in RCC can arise through several mechanisms, including direct renin secretion by the tumor (renin-secreting RCC), the tumor creating a mass effect on renal blood supply, decreasing it and activating the RAAS, or the presence of adrenal tissue within the tumor. Given these mechanisms, it is essential to consider renal tumors in the differential diagnosis of secondary hypertension. This case reports uncontrolled hypertension as the presenting complaint in a young female with a chromophobe RCC. Case Presentation: A 32-year-old female presented with intermittent headache, fatigue, and uncontrolled hypertension despite adherence to standard antihypertensive treatment. Laboratory tests revealed serum aldosterone at 37.9 ng/dL and markedly elevated plasma renin activity at 11.7 ng/mL/hr, suggesting hyperreninemic aldosteronism as the cause of her hypertension. A CT scan revealed a large, mildly enhancing mass in the upper pole of the left kidney, measuring 93 x 92 x 96 mm (Figure 1). Nephrectomy was discussed with the patient as part of her treatment plan and as a potential means of treating her hypertension. The patient consented, and the surgery was performed. Microscopic examination confirmed a chromophobe RCC extending into the renal sinus. Conclusion: This case underscores the importance of considering RCC in the differential diagnosis of secondary hypertension, even in young adults. Early recognition and surgical intervention, such as nephrectomy, are crucial, as they may alleviate hypertension and potentially serve as an early indicator for tumor detection before further progression.

Integrative genomic analyses identify neuroblastoma risk genes involved in neuronal differentiation

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

Vitamin D3 application and factors of its activity in the adrenal cortex of andropausal rats: A functionally-histological study

Introduction and aimVitamin D supplementation in aging subjects manifests a positive effect on various health-related parameters. We performed a functionally-histological analysis of the adrenal cortex regarding the factors of vitamin D activity and corticosterone output after vitamin D3 application in a rat model of the andropause. Material and methodsMiddle-aged Wistar rats were divided into sham operated (SO; n=8), orchidectomized (Orx; n=8) and vitamin D3-treated orchidectomized (Orx+vit. D; n=8) groups. Vitamin D3 (5 μg/kg b.m.) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using histochemistry/immunohistochemistry, stereology, ultrastructural and biochemical analyses. ResultsOrchidectomy (Orx) decreased the adrenal cortex-related volume densities of vascular (p<0,0001), vitamin D receptor (VDR; p<0,0166), cytochrome P450 oxidase 2R1 (CYP 2R1; p<0,0001) and cytochrome P450 oxidase 24 (CYP 24; p<0,0001) depots, but increased the volume density of cytochrome P450 27B1 (CYP 27B1; p<0,0001) depots. In Orx+vit. D rats, increase of the adrenal cortex-related volume densities of collagen (p<0,0001), VDR (p<0,0001) and CYP 2R1 (p<0,0001) depots as well as the lipid-droplet diameter (p<0,0001) in adrenocortical outer zona fasciculata cells was observed, while a decrease of volume densities of the vascular (p<0,0001), CYP 27B1 (p<0,0001) and CYP 24 (p<0,0001) depots was registered, all versus Orx group. Plasma level of ACTH was decreased (p=0,0155) and serum concentrations of 25-hydroxyvitamin D3 and corticosterone were increased (p<0,0001 and p=0,0187, respectively), all after the same treatment. ConclusionsIncreased corticosterone output after vitamin D3 application to andropausal rats appears not to be related to increased availability of 25-hydroxyvitamin D3 and decreased degradation of 1,25-dihydroxyvitamin D3 in adrenal tissue, but rather involves the central regulatory mechanisms.

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.

Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.

Role of Different Variants of Leptin Receptor in Human Adrenal Tumor Types.

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.

Disparate Effects of Stressors on Met-Enkephalin System Parameters and on Plasma Concentrations of Corticosterone in Young Female Chickens.

The effects of stressors were examined on Met-enkephalin-related parameters and plasma concentrations of corticosterone in 14-week-old female chickens. Water deprivation for 24 h was accompanied by a tendency for increased plasma concentration of Met-enkephalin while plasma concentrations of corticosterone were elevated in water-deprived birds. Concentrations of Met-enkephalin were reduced in the anterior pituitary gland and adrenal gland in water-deprived pullets while proenkephalin (PENK) expression was increased in both tissues. There were changes in the plasma concentrations of Met-enkephalin and corticosterone in pullets subjected to either feed withholding or crowding. Concentrations of Met-enkephalin were increased in the anterior pituitary gland but decreased in adrenal glands in pullets subjected to crowding stress. The increase in the plasma concentrations of Met-enkephalin was ablated when the chickens were pretreated with naltrexone. However, naltrexone did not influence either basal or crowding on plasma concentrations of corticosterone. In vitro release of Met-enkephalin from the anterior pituitary or adrenal tissues was depressed in the presence of naltrexone. It was concluded that Met-enkephalin was part of the neuroendocrine response to stress in female chickens. It was concluded that stress influenced the release of both Met-enkephalin and corticosterone, but there was not complete parallelism.