Preliminary investigation reveals novel pathological consequences of bluetongue virus-1 infection in the endocrine glands of pregnant Indian sheep.

Bluetongue virus (BTV), a major peril to the sheep industry, infects a wide range of the cells in the infected animals including mononuclear, dendritic and epithelial cells. However, little is known about its tropism for the secretory epithelial cells of endocrine glands and the pathogenesis it induces. The aim of the study was to assess the BTV load, antigen distribution in the tissue of the pituitary, thyroid as well as adrenal glands and associated histopathological consequences. BTV antigens were localized using immunohistochemistry in the thyroid's epithelial cells, zona fasciculata and zona reticularis cells and the anterior pituitary epithelial cells. The real-time PCR portrayed the high viral load in adrenals at 7th days postinoculation (DPI) and in thyroid and pituitary glands at 15th DPI. Serum examination revealed variation in the T-3 and T-4 of infected animals in comparison to the control group. Caspase-3 immunolocalization revealed BTV-1 induces apoptosis in the affected cells of endocrine gland of infected animals. Further, this study signifies the tropism of BTV in the novel sites (endocrine glands) of the host that might be one of the reasons for the poor performance of infected animals.

The neuroendocrine and endocrine systems in insect - Historical perspective and overview.

A complex cascade of events leads to the initiation and maintenance of a behavioral act in response to both internally and externally derived stimuli. These events are part of a transition of the animal into a new behavioral state, coordinated by chemicals that bias tissues and organs towards a new functional state of the animal. This form of integration is defined by the neuroendocrine (or neurosecretory) system and the endocrine system that release neurohormones or hormones, respectively. Here we describe the classical neuroendocrine and endocrine systems in insects to provide an historic perspective and overview of how neurohormones and hormones support plasticity in behavioral expression. Additionally, we describe peripheral tissues such as the midgut, epitracheal glands, and ovaries, which, whilst not necessarily being endocrine glands in the pure sense of the term, do produce and release hormones, thereby providing even more flexibility for inter-organ communication and regulation.

Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease.

Aquaporins (AQPs), transmembrane proteins permeable to water, are involved in gastrointestinal secretion. The secretory products of the glands are delivered either to some organ cavities for exocrine glands or to the bloodstream for endocrine glands. The main secretory glands being part of the gastrointestinal system are salivary glands, gastric glands, duodenal Brunner's gland, liver, bile ducts, gallbladder, intestinal goblet cells, exocrine and endocrine pancreas. Due to their expression in gastrointestinal exocrine and endocrine glands, AQPs fulfill important roles in the secretion of various fluids involved in food handling. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to gastrointestinal secretion.

Inflammatory and Infectious Disorders in Endocrine Pathology.

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.

The Comprehensive Steroidome in Complete TSPO/PBR Knockout Mice under Basal Conditions.

The 18 kDa translocator protein (TSPO/PBR) is a multifunctional evolutionary highly conserved outer mitochondrial membrane protein. Decades of research has reported an obligatory role of TSPO/PBR in both mitochondrial cholesterol transport and, thus, steroid production. However, the strict dependency of steroidogenesis on TSPO/PBR has remained controversial. The aim of this study was to provide insight into the steroid profile in complete C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout male mice (TSPO-KO) under basal conditions. The steroidome in the brain, adrenal glands, testes and plasma was measured by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). We found that steroids present in wild-type (WT) mice were also detected in TSPO-KO mice, including pregnenolone (PREG), progestogens, mineralo-glucocorticosteroids and androgens. The concentrations of PREG and most metabolites were similar between genotypes, except a significant decrease in the levels of the 5α-reduced metabolites of progesterone (PROG) in adrenal glands and plasma and of the 5α-reduced metabolites of corticosterone (B) in plasma in TSPO-KO compared to WT animals, suggesting other regulatory functions for the TSPO/PBR. The expression levels of the voltage-dependent anion-selective channel (VDAC-1), CYP11A1 and 5α-reductase were not significantly different between both groups. Thus, the complete deletion of the tspo gene in male mice does not impair de novo steroidogenesis in vivo.

Aquaporins in Glandular Secretion.

Exocrine and endocrine glands deliver their secretory product, respectively, at the surface of the target organs or within the bloodstream. The release of their products has been shown to rely on secretory mechanisms often involving aquaporins (AQPs). This chapter will provide insight into the role of AQPs in secretory glands located within the gastrointestinal tract, including salivary glands, gastric glands, duodenal Brunner's glands, liver, gallbladder, intestinal goblets cells, and pancreas, as well and in other parts of the body, including airway submucosal glands, lacrimal glands, mammary glands, and eccrine sweat glands. The involvement of AQPs in both physiological and pathophysiological conditions will also be highlighted.

Node-by-node diagnosis for multiple ipsilateral nodules by segmental adrenal venous sampling in primary aldosteronism.

OBJECTIVES: In patients with primary aldosteronism (PA), multiple adrenocortical nodules may be present on the surgical side. The aim of this study was to clarify the pathological diagnosis and the node-by-node diagnostic capability of segmental adrenal venous sampling (sAVS). DESIGN: Retrospective study. PATIENTS: A total of 162 patients who underwent adrenalectomy following sAVS were studied. MEASUREMENTS: Multiple nodules on the surgical side were extracted while referring to contrast-enhanced computed tomography images. We also performed a detailed histopathological analysis of the resected specimens from patients undergoing sAVS, which included immunohistochemistry for CYP11B2. RESULTS: In 11 (6.8%) patients, two to three nodules were detected on the surgical side. All patients were diagnosed by sAVS with at least one aldosterone-producing adenoma (APA) for localized aldosterone elevation in tributaries. Seven patients showed a lateralization index value of ≥4 after ACTH stimulation. Histopathologically and clinically, two patients had two or three CYP11B2-positive APAs, and the other nine patients both APAs and non-APAs. The positive predictive value of the most suspected APA, that is, the drainer that showed the highest aldosterone level by sAVS, was 11/11 (100%, 95% confidence interval [CI]: 71.5%-100%), while that for the second and third suspected APA was 3/7 (42.9%, 95% CI: 9.9%-81.6%), and they were significantly different (p = .01). Further, the positive predictive value of non-APA was 4/4 (100%, 95% CI: 39.8%-100%). CONCLUSIONS: The sAVS could correctly diagnose the aldosterone production in multiple ipsilateral adrenal nodules.

Autoimmunity in sarcoidosis: the tip of the Iceberg.

Sarcoidosis is a mysterious condition with an etiology that has to date eluded explanation. Innumerable clinical and serological organ- and non-organ-specific autoimmune associations have been reported. Many of the associated conditions are life-threatening but easily manageable if diagnosed early. Due to the long latency that precedes the clinical onset of autoimmune diseases, it is prudent to ensure a long follow-up and a broad viewing perspective while maintaining a high index of suspicion when viewing the autoimmunity iceberg in sarcoidosis.

Insights into the possible impact of COVID-19 on the endocrine system.

The novel 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible and pathogenic coronavirus. Because of the novelty of the COVID-19 pandemic, few data are available on the impact of the SARS-CoV-2 on the different endocrine glands. Previous studies of severe acute respiratory syndrome (SARS) have shown a harmful effect on endocrine function. Notably, the angiotensin-converting enzyme-2 receptor, which is the entry route of coronaviruses to the host cell, is widely expressed in the endocrine organs including testis, endocrine pancreas, thyroid, and adrenal, and pituitary glands. Clinical and biochemical manifestations have been recorded in COVID-19 patients resulting in changes in endocrine activities, which were also recorded during the SARS outbreak in 2003. This review aims to explore the impact of SARS-CoV-2 infection on the function of endocrine glands, based on the latest research in the field.

COVID-19 induced hypoparathyroidism: A case report.

Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.

Safe provision of elective endocrine surgery operations amid the COVID-19 crisis.

INTRODUCTION: The aim of this study was to determine the impact of the COVID-19 pandemic on the provision of clinical services (perioperative clinical outcomes and productivity) of the department of endocrine and general surgery at a teaching hospital in the UK. METHODS: A retrospective chart review was conducted of all patients who were operated in our department during two periods: 1 April to 31 October 2019 (pre-COVID-19 period) and 1 April to 31 October 2020 (COVID-19 period). The perioperative clinical outcomes and productivity of our department for the two time periods were compared. RESULTS: In the pre-COVID-19 period, 130 operations were carried out, whereas in the COVID-19 group, this reduced to 89. The baseline characteristics between the two groups did not significantly differ. Parathyroid operations decreased significantly by 68% between the two study periods. Overall, during the COVID-19 phase, the department maintained 68% of its operating workload compared with the respective 2019 time period. The clinical outcomes for the patients who had a thyroid/parathyroid/adrenal operation were not statistically different for the two study periods. There were no COVID-19 related perioperative complications for any of the operated patients and no patient tested positive for COVID-19 while an inpatient. For the COVID-19 group, the department maintained 67% of its outpatient appointments for endocrine surgery and 26% for general surgery pathologies. CONCLUSIONS: The COVID-19 pandemic significantly reduced the clinical activity of our department. However, it is possible to continue providing clinical services for urgent/cancer cases with the appropriate safety measures in place.

A review of systemic infiltrative diseases and associated endocrine diseases.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.

A narrative review of multiple endocrine neoplasia syndromes: genetics, clinical features, imaging findings, and diagnosis.

OBJECTIVE: We aimed to provide ideas for clinicians, especially radiologists, for the diagnosis of multiple endocrine neoplasia (MEN) syndromes. BACKGROUND: MEN syndromes include MEN1, MEN2, and MEN4 and usually involve 2 or more endocrine tumors. The MEN syndromes are a group of euchromatic dominant genetic diseases, and the main genes involved include MEN1 (MEN1), RET (MEN2), and CDKN1B (MEN4). METHODS: In this article, involving 8 cases (4 cases of MEN1, 2 cases of MEN2A, 1 case of MEN2B, 1 case of MEN4) from our center, we introduced the disease spectrum, clinical manifestations (especially imaging findings), and related genes involved in each type of MEN syndromes. We also discussed the differential diagnosis between MEN and sporadic tumors and emphasized that MEN should be screened and the relevant required examinations. CONCLUSIONS: Considering that MEN syndromes involve multiple endocrine gland tumors and nonendocrine organ diseases, it is very important to identify potential patients early and perform multiple examinations on them, including biochemical and multitype, and multisite imaging examinations according to the disease spectrum of each type. Considering that this is a group of genetic diseases, both interviewing patients about their family history and genetic testing are also very important. Only in this way can a comprehensive and accurate diagnosis be made, enabling patients to receive appropriate treatment and improve their prognosis.

A review of systemic infiltrative diseases and associated endocrine diseases. / Revisión sobre enfermedades infiltrativas sistémicas y patología endocrinológica asociada.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.

New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications.

The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a functional role by acting as an endogenous coagonist at N-methyl-D-aspartate receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, free D-Asp is abundant during prenatal life and decreases greatly after birth in concomitance with the postnatal onset of D-Asp oxidase expression, which is the only enzyme known to control endogenous levels of this molecule. Conversely, in the endocrine system, D-Asp concentrations enhance after birth during its functional development, thereby suggesting an involvement of the amino acid in the regulation of hormone biosynthesis. The substantial binding affinity for the NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp on NMDAR-mediated responses. Herein we review the physiological function of free D-Asp and of its metabolizing enzyme in regulating the functions of the brain and of the neuroendocrine system based on recent genetic and pharmacological human and animal studies.

D-Amino acids in mammalian endocrine tissues.

D-Aspartate, D-serine and D-alanine are a regular occurrence in mammalian endocrine tissues, though in amounts varying with the type of gland. The pituitary gland, pineal gland, thyroid, adrenal glands and testis contain relatively large amounts of D-aspartate in all species examined. D-alanine is relatively abundant in the pituitary gland and pancreas. High levels of D-serine characterize the hypothalamus. D-leucine, D-proline and D-glutamate are generally low. The current knowledge of physiological roles of D-amino acids in endocrine tissues is far from exhaustive, yet the topic is attracting increasing interest because of its potential in pharmacological application. D-aspartate is known to act at all levels of the hypothalamus-pituitary-testis axis, playing a key role in reproductive biology in several vertebrate classes. An involvement of D-amino acids in the endocrine function of the pancreas is emerging. D-Aspartate has been immunolocalized in insulin-containing secretory granules in INS-1 E clonal ß cells and is co-secreted with insulin by exocytosis. Specific immunolocalization of D-alanine in pituitary ACTH-secreting cells and pancreatic ß-cells suggests that this amino acid participates in blood glucose regulation in mammals. By modulating insulin secretion, D-serine probably participates in the control of systemic glucose metabolism by modulating insulin secretion. We anticipate that future investigation will significantly increase the functional repertoire of D-amino acids in homeostatic control.

CHEK2 Mutation in Patient with Multiple Endocrine Glands Tumors. Case Report.

BACKGROUND: Many studies show the occurrence of several multiple endocrine neoplasia syndromes caused by different mutations, for example, in MEN1 and RET genes. Nevertheless, there are less common mutations causing multiple endocrine glands tumors. Examples of such mutations are CHEK2 gene mutations, causing breast, kidney, gastric, colorectal, prostate, lung, ovarian, and thyroid cancers. CASE DESCRIPTION: In 2005, a 30-year-old woman was admitted to the hospital due to uncontrolled hypertension and obesity. Performed tests have shown ACTH (adrenocorticotropic hormone)-independent micronodular adrenal hyperplasia (AIMAH) as a cause. In 2010, the further diagnostic analysis revealed Cushing's disease caused by ACTH-secreting pituitary microadenoma. Additionally, in 2011, the patient underwent the strumectomy of multinodular struma. Papillary thyroid carcinoma was found in the excised tissue. In 2018, transvaginal ultrasonography revealed a tumor of the right ovary. After a performed hysterectomy with bilateral salpingo-oophorectomy, the histopathology result has shown female adnexal tumors of probable Wolffian origin (FATWO) located in the broad ligament of the uterus. Due to the history of multiglandular diseases, the patient was referred to genetic testing. We found a positive pathogenic mutation in CHEK2-suppressor gene involved in DNA repair, cell cycle arrest, and apoptosis in response to DNA damage. CONCLUSION: CHEK2 variants may predispose to a range of endocrine glands tumors, including those identified in our patient. Multiple endocrine glands tumors, as in the presented patient, are a serious problem of public health, due to numerous hospitalizations and necessary repeated surgical treatments. Moreover, the association between CHEK2 and ovarian cancer can be a serious problem with reproductive health.

Endocrine vigilance in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for a pandemic that emerged in December 2019. Heterogeneous clinical forms are described from asymptomatic to severe hypoxaemic acute respiratory syndrome with multisystem organ failure. The impact of this coronavirus disease 2019 on the endocrine glands remains unknown. However, the results of previous studies on viruses from the same family allow us to write proposals for patients followed for chronic endocrine diseases. Currently, if these subjects are infected with SARS-CoV-2, they must not stop their treatment. In some cases, hormone replacement doses have to be increased. In case of worsening clinical signs, hormonal biological monitoring must be done. This article will be helpful for improving the management of chronic endocrine diseases that could affect thyroid, adrenals, gonads and pituitary gland functions. Proposals could be applied in COVID-19 infected subjects or in those who have been in contact with COVID-19 infected people.

Our 2018 Cancer Cytopathology Young Investigator.

BACKGROUND: The Paris System for Urine Cytopathology (the Paris System) has succeeded in making the analysis of liquid-based urine preparations more reproducible. Any algorithm seeking to automate this system must accurately estimate the nuclear-to-cytoplasmic (N:C) ratio and produce a qualitative "atypia score." The authors propose a hybrid deep-learning and morphometric model that reliably automates the Paris System. METHODS: Whole-slide images (WSI) of liquid-based urine cytology specimens were extracted from 51 negative, 60 atypical, 52 suspicious, and 54 positive cases. Morphometric algorithms were applied to decompose images to their component parts; and statistics, including the NC ratio, were tabulated using segmentation algorithms to create organized data structures, dubbed rich information matrices (RIMs). These RIM objects were enhanced using deep-learning algorithms to include qualitative measures. The augmented RIM objects were then used to reconstruct WSIs with filtering criteria and to generate pancellular statistical information. RESULTS: The described system was used to calculate the N:C ratio for all cells, generate object classifications (atypical urothelial cell, squamous cell, crystal, etc), filter the original WSI to remove unwanted objects, rearrange the WSI to an efficient, condensed-grid format, and generate pancellular statistics containing quantitative/qualitative data for every cell in a WSI. In addition to developing novel techniques for managing WSIs, a system capable of automatically tabulating the Paris System criteria also was generated. CONCLUSIONS: A hybrid deep-learning and morphometric algorithm was developed for the analysis of urine cytology specimens that could reliably automate the Paris System and provide many avenues for increasing the efficiency of digital screening for urine WSIs and other cytology preparations.