Adrenal Tissue Research Articles

Clinical indications, safety, and effectiveness of percutaneous image-guided adrenal mass biopsy: an 8-year retrospective analysis in 160 patients.

To assess indications, safety, and effectiveness of percutaneous adrenal mass biopsy in contemporary practice. This institutional review board-approved, retrospective study included all patients undergoing percutaneous image-guided adrenal mass biopsies at an academic health system from January 6, 2015, to January 6, 2023. Patient demographics, biopsy indications, mass size, laboratory data, pathology results, and complications were recorded. Final diagnoses were based on pathology or ≥ 1 year of imaging follow-up when biopsy specimens did not yield malignant tissue. Test performance calculations excluded repeat biopsies. Continuous variables were compared with Student's t test, dichotomous variables with chi-squared test. A total of 160 patients underwent 186 biopsies. Biopsies were indicated to diagnose metastatic disease (139/186; 74.7%), for oncologic research only (27/186; 14.5%), diagnose metastatic disease and oncologic research (15/186; 8%), and diagnose an incidental adrenal mass (5/186; 2.7%). Biopsy specimens were diagnostic in 154 patients (96.3%) and non-diagnostic in 6 (3.8%). Diagnostic biopsies yielded malignant tissue (n = 136), benign adrenal tissue (n = 12), and benign adrenal neoplasms (n = 6) with sensitivity = 98.6% (136/138), specificity = 100% (16/16), positive predictive value = 100% (136/136), and negative predictive value = 88.9% (16/18). Adverse events followed 11/186 procedures (5.9%) and most minor (7/11, 63.6%). The adverse event rate was similar whether tissue was obtained for clinical or research purposes (10/144; 6.9% vs. 1/42; 2.4%, p = 0.27), despite more specimens obtained for research (5.8 vs. 3.7, p < 0.001). Percutaneous adrenal mass biopsy is safe, accurate, and utilized almost exclusively to diagnose metastatic disease or for oncologic research. The negative predictive value is high when diagnostic tissue samples are obtained. Obtaining specimens for research does not increase adverse event risk.

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment.

Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan-Meier method with the log-rank test. Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P<0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS. IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.

The importance of novel histopathological classification and its association with outcomes of primary aldosteronism: What you need to know from a urologist’s perspective

Primary aldosteronism (PA), the most important cause of secondary endocrine hypertension, is hallmarked by excessive aldosterone secretion. There were 2 subtypes of PA—unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia, which are now outdated. Since conventional adrenal pathological reports only examined hematoxylin and eosin staining, the secretory function of the structural adenoma(s) could not be determined. Several enzymes produce aldosterone-related steroids, and 2 isoforms of 11β-hydroxylase, namely CYP11B1 and CYP11B2 (aldosterone synthase), are responsible for producing cortisol and aldosterone, respectively. Since the availability of specifically selective antibodies for targeting CYP11B1 and CYP11B2, the diagnosis/nomenclature of PA-related adrenal pathology has been revolutionized by using immunohistochemistry staining for CYP11B2 to identify the aldosterone production site in the human adrenal cortex. The significance of immunohistochemical staining of formalin-fixed paraffin-embedded adrenal tissue sections has become “mandatory” for precisely detecting the lesions responsible for PA. Recently, the histopathology of PA consensus, based on immunochemical findings, was established to define the nomenclature and adrenal histopathological features in unilateral PA. In this study, we further investigate the association between the pathological subtypes and the surgical outcomes of PA as per the criteria of the Primary Aldosteronism Surgery Outcome consensus. Unfortunately, a significant lag is seen in the adaptation of Taiwan’s pathologists to the histopathology of PA consensus. Furthermore, a strong push from all urologists across Taiwan and the governmental health care authorities is required to elevate the care level provided to all patients with PA in Taiwan to exceptional.

Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice

Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.

Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia.

Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis. We aimed to evaluate the role of the immune system and hormones that accumulate in poorly controlled CAH in the development of AML. When compared to normal adrenal tissue, CAH-affected adrenal tissue and myelolipomas showed an increased expression of inflammatory cells (CD68, IL2Rbeta), stem cells (CD117) B cells (IRF4), and adipogenic markers (aP2/FABP4, AdipoQ, PPARγ, Leptin, CideA), and immunostaining showed nodular lymphocytic accumulation. Immunohistochemistry staining revealed a higher density of inflammatory cells (CD20, CD3, CD68) in CAH compared to non-CAH myelolipomas. In vitro RNA-sequencing studies using NCI-H295R adrenocortical cells with exogenous exposure to ACTH, testosterone, and 17-hydroxyprogesterone hormones, showed the differential expression of genes involved in cell cycle progression, phosphorylation, and tumorigenesis. Migration of B-lymphocytes was initiated after the hormonal treatment of adrenocortical cells using the Boyden chamber chemotaxis assay, indicating a possible hormonal influence on triggering inflammation and the development of myelolipomas. These findings demonstrate the important role of inflammation and the hormonal milieu in the development of AML in CAH.

The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues and extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can provide essential knowledge for the development of better therapeutic and tumor management strategies, especially for those with advanced and metastatic PPGLs. The first part of this review outlines the fundamental principles of the immune system and tumor microenvironment, and their role in cancer immunoediting, particularly emphasizing PPGLs. We focus on how the unique pathophysiology of PPGLs, such as their high molecular, biochemical, and imaging heterogeneity and production of several oncometabolites, creates a tumor-specific microenvironment and immunologically "cold" tumors. Thereafter, we discuss recently published studies related to the reclustering of PPGLs based on their immune signature. The second part of this review discusses future perspectives in PPGL management, including immunodiagnostic and promising immunotherapeutic approaches for converting "cold" tumors into immunologically active or "hot" tumors known for their better immunotherapy response and patient outcomes. Special emphasis is placed on potent immune-related imaging strategies and immune signatures that could be used for the reclassification, prognostication, and management of these tumors to improve patient care and prognosis. Furthermore, we introduce currently available immunotherapies and their possible combinations with other available therapies as an emerging treatment for PPGLs that targets hostile tumor environments.

Ectopic adrenal tissue in a cat that underwent an ovariohysterectomy.

To describe the use of ultrasound and adrenal function testing to confirm that excised periovarian tissue is normal ectopic adrenal tissue (EAT). A 6-month-old female domestic shorthair cat. The cat underwent an ovariohysterectomy procedure, during which abnormal tissue was discovered adjacent to both ovaries. The tissue was removed during the ovariohysterectomy and submitted for histopathology, which was consistent with adrenal gland tissue, initially raising concern for an inadvertent adrenalectomy. Abdominal ultrasound and an adrenal function test were performed that confirmed normal adrenal structure and function; thus, the removed structure was diagnosed as EAT. The patient continued to recover from the procedure uneventfully at home. Parovarian nodules are an uncommon finding but when observed and biopsied, may be mistaken for physiologic adrenal tissue on the basis of histopathologic features alone without awareness of their existence and clinical context. The use of abdominal ultrasound and ACTH stimulation test offers an affirmative method of differentiating adrenal gland tissue from EAT.

Bilateral adrenal histoplasmosis in a Malaysian tertiary hospital: Report of four cases

Rationale: Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency. Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues. Patients concerns: We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses. Diagnoses: Bilateral adrenal histoplasmosis. Interventions: Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment. Outcomes: Two patients’ adrenal function recovered not requiring any steroid replacement, while 1 patient still requires long-term steroid replacement. Lessons: Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency. Usually patients have an exposure to bird droppings, bat guano or soil contaminated with histoplasmosis fungi. Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

Intra-adrenal Paraganglioma and Paraaortic Paraganglioma in 15 Years Old Boys

Intra-adrenal paraganglioma (also called pheochromocytoma) is a chromaffin cell tumor that arises in the adrenal medulla and produces excess catecholamines. Paraganglioma can also be located in the extra-adrenal area. The incidence rate of intra-adrenal and extra-adrenal paraganglioma is about 1 case per 2.500-6.500 population, highest incidence at 40-50 years old, and distribution is the same in males and females. Intra-adrenal paraganglioma in pediatrics is more familial, bilateral, multifocal, and malignant. In children, the incidence rate of these tumors was 8.86%, the ratio of boys to girls was 2:1, and the average age of 11. This article reports a case, of a 15 years old boy with severe headaches, recurrent seizures, and a hypertension crisis (143/103-220/110 mmHg). MSCT scan of abdominal showed solid mass heterogeneous with central necrotic multiple in the supero-anterior of the left and right kidneys and on the right anterolateral aorta as high as CV L2, impressive adrenal gland mass and extra-adrenal, suspect pheochromocytoma. Performed surgery, routine histopathological examination, and Immunohistochemistry. Macroscopic examination showed an oval round shape mass of left and right adrenal tumors as well as the paraaortic, a smooth outer surface of the capsular, with yellowish brown color mass tumor at cut surface, supple consistency. Microscopic examination showing adrenal gland and paraaortic tissue with fibrous capsule contains proliferation of neoplastic cells forming a nested alveolar (Zellballen) pattern with a round oval to polygonal cells, granular eosinophilic cytoplasm, round oval nuclei, surrounded by sustentacular cells. Chromogranin A and S-100 are positive. The case was concluded by clinical findings, histopathological, and immunohistochemistry as intra-adrenal paraganglioma and paraganglioma of paraaortic.

Impaired Expression of Humanin during Adrenocortical Carcinoma.

The discovery of mitochondria-derived peptides (MDPs) has provided a new perspective on mitochondrial function. MDPs encoded by mitochondrial DNA (mtDNA) can act as hormone-like peptides, influencing cell survival and proliferation. Among these peptides, humanin has been identified as a crucial factor for maintaining cell survival and preventing cell death under various conditions. Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy that results from adrenal hormone dysfunction. This study aimed to investigate humanin expression in the adrenal tissue and serum of patients with ACC. For the first time, our study revealed significant reduction in the mRNA expression of humanin in patients with ACC compared to healthy controls. However, no significant changes were observed in the serum humanin levels. Interestingly, we identified a positive correlation between patient age and serum humanin levels and a negative correlation between tumor size and LDL levels. While the impaired expression of humanin in patients with ACC may be attributed to mitochondrial dysfunction, an alternative explanation could be related to diminished mitochondrial copy number. Further investigations are warranted to elucidate the intricate relationship among humanin, mitochondrial function, and ACC pathology.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Vascular endothelial growth factor and endocan expression in adrenal cortical tumors and their relationship with histopathological prognostic parameters.

The aim of this study was to determine the tissue expressions of vascular endothelial growth factor (VEGF) and endocan in adrenal cortical tumors and the factors associated with them. The study included 6 subjects with adrenocortical adenoma (ACA), 7 subjects with adrenocortical carcinoma (ACC), and 13 control subjects with a normal adrenal cortex. The status of VEGF and endocan expression was determined by the proportions of cells staining on a scale ranging from negative (not staining at all) to strongly positive. VEGF expression was detected in 1 (16.7%) of 6 subjects in the ACA group and in 6 (85.7%) of 7 subjects in the ACC group. VEGF expression was not detected in any of the subjects in the control group. Endocan expression was detected in 6 (100%) of 6 subjects in the ACA group and in 7 (100%) of 7 subjects in the ACC group, while it was detected in only 4 (30.7%) of 13 subjects in the control group. VEGF was expressed with a high frequency in subjects with ACC and with a low frequency in subjects with ACA, but it was not expressed in subjects with normal adrenal cortex tissue. Although endocan was expressed with a higher frequency in subjects with ACC and ACA, it was also expressed in subjects with normal adrenal cortex tissue. The percentage of cells expressed endocan in subjects with ACC was also significantly higher than in subjects with both ACA and normal adrenal cortex.

Adaptive remodeling of the stimulus-secretion coupling: Lessons from the 'stressed' adrenal medulla.

Stress is part of our daily lives and good health in the modern world is offset by unhealthy lifestyle factors, including the deleterious consequences of stress and associated pathologies. Repeated and/or prolonged stress may disrupt the body homeostasis and thus threatens our lives. Adaptive processes that allow the organism to adapt to new environmental conditions and maintain its homeostasis are therefore crucial. The adrenal glands are major endocrine/neuroendocrine organs involved in the adaptive response of the body facing stressful situations. Upon stress episodes and in response to activation of the sympathetic nervous system, the first adrenal cells to be activated are the neuroendocrine chromaffin cells located in the medullary tissue of the adrenal gland. By releasing catecholamines (mainly epinephrine and to a lesser extent norepinephrine), adrenal chromaffin cells actively contribute to the development of adaptive mechanisms, in particular targeting the cardiovascular system and leading to appropriate adjustments of blood pressure and heart rate, as well as energy metabolism. Specifically, this chapter covers the current knowledge as to how the adrenal medullary tissue remodels in response to stress episodes, with special attention paid to chromaffin cell stimulus-secretion coupling. Adrenal stimulus-secretion coupling encompasses various elements taking place at both the molecular/cellular and tissular levels. Here, I focus on stress-driven changes in catecholamine biosynthesis, chromaffin cell excitability, synaptic neurotransmission and gap junctional communication. These signaling pathways undergo a collective and finely-tuned remodeling, contributing to appropriate catecholamine secretion and maintenance of body homeostasis in response to stress.

Effects of transcription factor SOX11 on the biological behavior of neuroblastoma cell and potential regulatory mechanism.

This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.

Alterations in Serum miR-126-3p Levels over Time: A Marker of Pituitary Insufficiency following Head Trauma

Introduction: Traumatic brain injuries (TBIs) pose a high risk of pituitary insufficiency development in patients. We have previously reported alterations in miR-126-3p levels in sera from patients with TBI-induced pituitary deficiency. Methods: To investigate why TBI-induced pituitary deficiency develops only in some patients and to reveal the relationship between miR-126-3p with hormone axes, we used mice that were epigenetically modified with miR-126-3p at the embryonic stage. These modified mice were subjected to mild TBI (mTBI) according to the Marmarou’s weight-drop model at 2 months of age. The levels of miR-126-3p were assessed at 1 and 30 days in serum after mTBI. Changes in miR-126-3p levels after mTBI of wild-type and miR-126-3p* modified mouse lines validated our human results. Additionally, hypothalamus, pituitary, and adrenal tissues were analyzed for transcripts and associated serum hormone levels. Results: We report that miR-126-3p directly affects hypothalamus-pituitary-adrenal (HPA) axis upregulation and ACTH secretion in the acute phase after mTBI. We also demonstrated that miR-126-3p suppresses Gnrh transcripts in the hypothalamus and pituitary, but this is not reflected in serum FSH/LH levels. The increase in ACTH levels in the acute phase may indicate that upregulation of miR-126-3p at the embryonic stage has a protective effect on the HPA axis after TBI. Notably, the most prominent transcriptional response is found in the adrenals, highlighting their role in the pathophysiology of TBI. Conclusion: Our study revealed the role of miR-126-3p in TBI and pituitary deficiency developing after TBI, and the obtained data will significantly contribute to elucidating the mechanism of pituitary deficiency development after TBI and development of new diagnostic and treatment strategies.

Retroperitoneoscopic enucleation adrenalectomy: a viable surgical option for small nonsecreting adrenal tumors with low potential of malignancy.

Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.

The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 catalyzes the activation of testosterone

Testosterone biosynthesis from its precursor androstenedione is thought to be exclusively catalysed by the 17β-hydroxysteroid dehydrogenases—HSD17B3 in testes, and AKR1C3 in the ovary, adrenal and peripheral tissues. Here we show for the first time that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) can also catalyse the 17β-reduction of androstenedione to testosterone, using a combination of in vitro enzyme kinetic assays, mathematical modelling, and molecular docking analysis. Furthermore, we show that co-expression of HSD11B1 and AKR1C3 increases testosterone production several-fold compared to the rate observed with AKR1C3 only, and that HSD11B1 is likely to contribute significantly to testosterone production in peripheral tissues.

Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System.

Knowledge of circadian rhythm clock gene expression outside the suprachiasmatic nucleus is increasing. The purpose of this study was to determine whether expression of circadian clock genes differed within or among the bovine stress axis tissues (e.g., amygdala, hypothalamus, pituitary, adrenal cortex, and adrenal medulla). Tissues were obtained at an abattoir from eight mature nonpregnant Brahman cows that had been maintained in the same pasture and nutritional conditions. Sample tissues were stored in RNase-free sterile cryovials at -80 °C until the total RNA was extracted, quantified, assessed, and sequenced (NovaSeq 6000 system; paired-end 150 bp cycles). The trimmed reads were then mapped to a Bos taurus (B. taurus) reference genome (Umd3.1). Further analysis used the edgeR package. Raw gene count tables were read into RStudio, and low-expression genes were filtered out using the criteria of three minimum reads per gene in at least five samples. Normalization factors were then calculated using the trimmed mean of M values method to produce normalized gene counts within each sample tissue. The normalized gene counts important for a circadian rhythm were analyzed within and between each tissue of the stress axis using the GLM and CORR procedures of the Statistical Analysis System (SAS). The relative expression profiles of circadian clock genes differed (p < 0.01) within each tissue, with neuronal PAS domain protein 2 (NPAS2) having greater expression in the amygdala (p < 0.01) and period circadian regulator (PER1) having greater expression in all other tissues (p < 0.01). The expression among tissues also differed (p < 0.01) for individual circadian clock genes, with circadian locomotor output cycles protein kaput (CLOCK) expression being greater within the adrenal tissues and nuclear receptor subfamily 1 group D member 1 (NR1D1) expression being greater within the other tissues (p < 0.01). Overall, the results indicate that within each tissue, the various circadian clock genes were differentially expressed, in addition to being differentially expressed among the stress tissues of mature Brahman cows. Future use of these findings may assist in improving livestock husbandry and welfare by understanding interactions of the environment, stress responsiveness, and peripheral circadian rhythms.

Unilateral adrenalectomy for a drug-resistant bilateral primary aldosteronism with heart failure: pathophysiology and surgical indication

BackgroundPatients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy.Case presentationA 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient’s heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient’s heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment.ConclusionsUnilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.