AVP-eGFP was significantly upregulated by hypovolemia in the parvocellular division of the paraventricular nucleus in the transgenic rats.

Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.

Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure.

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.

Evaluating the impact of COVID-19 on male reproduction.

Invasion or damage of the male reproductive system is one of the reported outcomes of viral infection. Current studies have documented that SARS-CoV-2, which causes COVID-19, can damage the male reproductive system in large part by inflammatory damage caused by a cytokine storm. However, whether SARS-CoV-2 can infect the human testis directly and enter semen is controversial. Other adverse effects of SARS-CoV-2 on male reproduction are also of concern and require comprehensive evaluation. Here, we analyze the invasiveness of SARS-CoV-2 in the testis and examine reported mechanisms by which SARS-CoV-2 interferes with male reproduction. Long-term implications of SARS-CoV-2 infection on male reproduction are also discussed. It should be emphasized that although COVID-19 may induce testicular damage, a substantial decrease in male reproductive capacity awaits clinical evidence. We propose that there is an urgent need to track male COVID-19 patients during their recovery. The development of suitable experimental models, including human reproductive organoids, will be valuable to further investigate the viral impact on reproduction for current and future pandemics.

Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities.

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.

Cortisol level dysregulation and its prevalence-Is it nature's alarm clock?

This review examines the stress hormone cortisol which plays an important role in regulating and supporting different bodily functions. Disruption in cortisol production has an impact on health and this review looks at a wide range of papers where cortisol has been indicated as a factor in numerous chronic conditions-especially those which are classed as "noncommunicable diseases" (NCDs). Timely detection, screening, and treatment for NCDs are vital to address the growing problem of NCDs worldwide-this would have health and socioeconomic benefits. Interestingly, many of the papers highlight the pro-inflammatory consequences of cortisol dysregulation and its deleterious effects on the body. This is particularly relevant given the recent findings concerning COVID-19 where pro-inflammatory cytokines have been implicated in severe inflammation.

What we have to know about corticosteroids use during Sars-Cov-2 infection.

PURPOSE: Glucocorticoids (GCs), alone or associated to other drugs, were widely used in the management of patients affected by severe acute respiratory syndrome caused by SARS-CoV-2 infection, during the recent COVID-19 outbreak. This review summarizes the available data on HPA axis impairment in GC-treated SARS-CoV-2 patients, focusing on the risk of adrenal insufficiency and on potential drug interactions during concomitant treatments. METHODS: Literature on the impact of GCs therapy on HPA axis and on the consequences of coadministration of GCs and other drugs in SARS-CoV-2 patients has been reviewed. RESULTS: GC treatment can cause symptoms of hypercortisolism, especially in patients with individual hypersensibility, or hypoadrenalism after drug withdrawal, due to hypothalamic-pituitary-adrenal (HPA) axis suppression, with consequences in terms of increased morbidity and mortality risk. On the other hand, in SARS-CoV-2-infected patient's cortisol secretion could be insufficient also due to critical illness-related corticosteroid insufficiency (CIRCI). In addition, in this clinical context, the co-administration of antiretroviral drugs and corticosteroids may trigger drug-drug interaction and enhance the exposure to the latter ones, metabolized through the CYP450 CYP3A pathway, severely impacting on HPA axis. CONCLUSION: Physicians involved in the management of patients affected by COVID-19 should be aware of the need of an appropriate GC dose tapering, and of potential interaction of GCs with antiviral therapy and drugs used to treat associated co-morbidities.