In a recent study published in Microorganisms, researchers briefly outlined how viral infections trigger endocrinopathies in humans.
Viruses can transiently or permanently damage endocrine organs by directly attacking endocrine cells or via indirect mechanisms. It activates the antiviral immune response in the host organism, leading to local or systemic inflammation or organ-specific autoimmunity resulting in certain endocrinopathies.
Aggregating more data on viruses-induced endocrinopathies could open new avenues for the control of endocrine diseases. The researchers curated data on the effects of six different viruses on the human endocrine system.
First and foremost, they compiled data on how human coronaviruses (hCoVs), mainly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV damage the endocrine system. These two viruses share 80% identity and enter host cells by binding their spike (S) protein to angiotensin-converting enzyme 2 (ACE2), highly expressed in several endocrine glands, such as the hypothalamus, the pituitary, the thyroid, and the adrenal glands.
These viruses, especially SARS-CoV-2, disturb the main hypothalamic-pituitary-adrenal (HPA) axis, the human neuroendocrine system, that regulates homeostasis by stimulating the hypothalamus to secrete corticotropin-releasing hormone (CRH). It also stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH), which, in turn, triggers cortisol secretion from the adrenal glands.
Similarly, SARS-CoV-2 infections disturb prolactin, growth hormone (GH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) levels. Studies have also associated SARS-CoV-2 infection-induced increased serum levels of interleukin-6 (IL-6) with hyponatremia, an electrolyte disorder. The increased Il-6 levels might also be causing thyrotoxicosis and low serum TSH in coronavirus disease 2019 (COVID-19) patients.
Studies have not excluded the possibility that, like SARS-CoV, SARS-CoV-2 mimics the amino acid sequences of host ACTH to trigger the production of antiviral antibodies similar to anti-ACTH autoantibodies. Studies examining deceased COVID-19 patients using immunohistochemistry found SARS-CoV-2 in the pancreas, in both exocrine and endocrine cells.
Intriguingly, recent ex vivo studies have shown that SARS-CoV-2 can replicate in human pancreatic islets, damaging β-cell function, including glucose-stimulated insulin secretion. COVID-19 decrease sex hormone levels in men, including testosterone, suggesting defective Leydig cell function. Similarly, COVID-19 in women could result in irregular menstruation, abnormally heavy periods, and even postmenopausal bleeding in long COVID cases. It might be due to transient changes in sex hormones during the disease.
Doctors used steroids and low-molecular-weight heparin (LMWH) to manage severe COVID-19, which triggered hyperglycemia and insulin resistance in many patients. In the long term, glucocorticosteroid therapy inhibits LH and FSH secretion, leading to secondary osteoporosis in women. Similarly, LMWH, which prevents hypercoagulability during severe COVID-19, interferes with serum-free thyroid hormones. It is, thus, crucial to follow up with COVID-19 patients for endocrinopathies.
Over 38 million people worldwide were human immunodeficiency virus (HIV) infected in 2021. HIV has been shown to cause aberrant cortisol response to ACTH, testosterone deficits, and euthyroid sick syndrome. HIV-caused opportunistic infections adversely affect the pituitary gland or hypothalamus, causing hypogonadism in men. Other contributing factors are weight loss, poor nutrition, and cytokine effects.
Another endocrine disorder observed in HIV patients is an increased risk of type 2 diabetes (T2D). Drugs used to treat HIV infection, e.g., protease inhibitors, also cause insulin resistance and diabetes. Some other drugs, e.g., ketaconazole, used to treat HIV-associated fungal infections, increase steroid clearance and induce menstrual cycle disturbances in women and hypogonadism in men.
Studies have also associated chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections with endocrine disorders, such as autoimmune thyroiditis, T2D, and erectile dysfunction (ED). In addition, chronic HCV infection increases the likelihood of hypothyroidism. The HCV-induced inflammatory process may lead to the destruction of thyroid follicular cells and the appearance of autoimmune thyroiditis or thyroid cancer. Likewise, chronic HBV infections trigger increased serum TSH levels while lowering free triiodothyronine (FT3) and free thyroxine (FT4) levels.
Patients with chronic HCV infection also have low serum levels of total testosterone and aberrant sperm parameters, including low sperm volume, count, and motility, suggesting the negative influence of HCV on spermatogenesis. Drugs for treating HCV infection use interferon-α (IFN-α), known for its deleterious effects on the thyroid gland.
Lastly, the researchers described the effects of orthohantaviruses on the endocrine system. These viruses [e.g., Puumala virus (PUUV)] are known to cause severe human diseases, such as hemorrhagic fever with renal syndrome (HFRS). In 58 to 72% of HFRS patients, radiographic imaging has revealed necrotic and hemorrhagic damage of the pituitary gland and hypopituitarism during the infection cycle.
The ubiquitous human parvovirus B19 (PVB19) mainly transmits through the respiratory tract and blood transfusion causing many endocrine disorders in children, e.g., erythema infectiosum. Studies have also associated acute PVB19 infection with the appearance of Hashimoto’s thyroiditis (HT). Its genome persists in the thyroid of patients with autoimmune thyroid diseases (AITD), likely initiating the intrathyroidal inflammatory process.
Several studies have suggested that coxsackievirus B (CVB), an enterovirus (EV) species, is likely involved in T1D pathogenesis. CVB initiates autoimmunity against pancreatic β cells through molecular mimicry, activation of pre-existing autoreactive T cells, and altering tolerance to β-cell antigens resulting from thymus infection.
Furthermore, studies have suggested that EV infection leads to thyroid diseases. Maternal EV infection has been linked to the development of thyroiditis or AITD in neonates. Also, studies have documented hypothyroidism in 60% of children with antibodies against EV.
To conclude, more clinical data is needed to determine how to manage post-viral endocrinopathies. Future studies should also aim at clarifying the pathophysiological mechanisms by which viruses trigger endocrine disorders to develop new strategies for their prevention and treatment.
- Nekoua, M. et al. (2023) "Viruses and Endocrine Diseases", Microorganisms, 11(2), p. 361. doi: 10.3390/microorganisms11020361. https://www.mdpi.com/2076-2607/11/2/361
Posted in: Medical Science News | Medical Research News | Disease/Infection News
Tags: ACE2, Amino Acid, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Autoantibodies, Autoimmunity, Bleeding, Blood, Blood Transfusion, Cancer, Cell, Children, Chronic, Coronavirus, Coronavirus Disease COVID-19, Cortisol, covid-19, Cytokine, Diabetes, Drugs, Electrolyte, Endocrine, Enterovirus, Enzyme, Erectile Dysfunction, Erythema, Ex Vivo, Fever, Genome, Glucose, Growth Hormone, HBV, Hemorrhagic Fever, Heparin, Hepatitis, Hepatitis B, Hepatitis B Virus, Hepatitis C, HIV, Hormone, Hyperglycemia, Hypogonadism, Hyponatremia, Hypopituitarism, Hypothalamus, Hypothyroidism, Imaging, Immune Response, Immunodeficiency, Immunohistochemistry, Inflammation, Insulin, Insulin Resistance, Interferon, Interleukin, Interleukin-6, Menstruation, Nutrition, Osteoporosis, Pancreas, Parvovirus, Pituitary Gland, Prolactin, Protein, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Sperm, Steroid, Syndrome, Testosterone, Thymus, Thyroid, Thyroid Cancer, Thyroiditis, Type 2 Diabetes, Virus, Weight Loss
Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.
Source: Read Full Article