{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:20:01Z","timestamp":1793035201632,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["#P3-0298"],"award-info":[{"award-number":["#P3-0298"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P1-0170"],"award-info":[{"award-number":["P1-0170"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic\u2013pituitary\u2013adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.<\/jats:p>","DOI":"10.3390\/ijms23137326","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:21:50Z","timestamp":1656634910000},"page":"7326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["The Relationship between COVID-19 and Hypothalamic\u2013Pituitary\u2013Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess\u2014The CAPISCO International Expert Panel"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-8803","authenticated-orcid":false,"given":"Mojca","family":"Jensterle","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6053-5686","authenticated-orcid":false,"given":"Rok","family":"Herman","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-5254","authenticated-orcid":false,"given":"Andrej","family":"Jane\u017e","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-9910","authenticated-orcid":false,"given":"Wael Al","family":"Mahmeed","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute, Cleveland Clinic, Abu Dhabi P.O. Box 112412, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-1236","authenticated-orcid":false,"given":"Khalid","family":"Al-Rasadi","sequence":"additional","affiliation":[{"name":"Medical Research Center, Sultan Qaboos University, Muscat 113, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Al-Alawi","sequence":"additional","affiliation":[{"name":"Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat 113, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), 90-419 Lodz, Poland"},{"name":"Polish Mother\u2019s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland"},{"name":"Cardiovascular Research Centre, University of Zielona Gora, 65-417 Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-8893","authenticated-orcid":false,"given":"Yajnavalka","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Mohamed Bin Rashid University, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ceriello","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, 20099 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1029-2604","authenticated-orcid":false,"given":"Mustafa","family":"Cesur","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Ankara G\u00fcven Hospital, 06540 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Unit of Cardiology, Karolinska Institute and Karolinska University Hospital, University of Stockholm, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Galia","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bind), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Yen","family":"Goh","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Bharti Hospital & BRIDE, Karnal 132001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kempler","sequence":"additional","affiliation":[{"name":"Department of Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-0961","authenticated-orcid":false,"given":"Nader","family":"Lessan","sequence":"additional","affiliation":[{"name":"The Research Institute, Imperial College London Diabetes Centre, Abu Dhabi P.O. Box 48338, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Lotufo","sequence":"additional","affiliation":[{"name":"Center for Clinical and Epidemiological Research, University Hospital, University of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7320-785X","authenticated-orcid":false,"given":"Nikolaos","family":"Papanas","sequence":"additional","affiliation":[{"name":"Diabetes Center, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupoli, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3714-0790","authenticated-orcid":false,"given":"Ali A.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul D.","family":"Santos","sequence":"additional","affiliation":[{"name":"The Heart Institute (InCor), University of Sao Paulo Medical School Hospital, S\u00e3o Paulo 05403-000, Brazil"},{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0555-526X","authenticated-orcid":false,"given":"Anca P.","family":"Stoian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Diabetes, Nutrition and Metabolic Diseases, Carol Davila University, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5810-5460","authenticated-orcid":false,"given":"Peter P.","family":"Toth","sequence":"additional","affiliation":[{"name":"Cicarrone Center for the Prevention of Cardiovascular Disease, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Chennai 600013, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s12020-021-02734-w","article-title":"COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology","volume":"72","author":"Marazuela","year":"2021","journal-title":"Endocrine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"bqab203","DOI":"10.1210\/endocr\/bqab203","article-title":"Impact of COVID-19 on the Endocrine System: A Mini-review","volume":"163","author":"Clarke","year":"2021","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e499","DOI":"10.7861\/clinmed.2021-0200","article-title":"Interplay between endocrinology, metabolism and COVID-19 infection","volume":"21","author":"Mung","year":"2021","journal-title":"Clin. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106080","DOI":"10.1016\/j.ijantimicag.2020.106080","article-title":"COVID-19 treatment: Close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2)","volume":"56","author":"Song","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30009","DOI":"10.1073\/pnas.2021128117","article-title":"In fatal COVID-19, the immune response can control the virus but kill the patient","volume":"117","author":"Casadevall","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s40618-020-01384-5","article-title":"What we have to know about corticosteroids use during Sars-Cov-2 infection","volume":"44","author":"Ceccato","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/a-1300-2550","article-title":"The Role of Glucocorticoids in the Management of COVID-19","volume":"53","author":"Alexaki","year":"2021","journal-title":"Horm. Metab. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.21037\/atm-21-1783","article-title":"Tailoring glucocorticoids in patients with severe COVID-19: A narrative review","volume":"9","author":"Luo","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/phar.2637","article-title":"Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review","volume":"42","author":"Landolf","year":"2022","journal-title":"Pharmacotherapy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_11","unstructured":"World Health Organization (2020). Clinical Management of Severe Acute Respiratory Infection when Novel Coronavirus (2019-nCoV) Infection is Suspected: Interim Guidance, 28 January 2020, World Health Organization. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/330893."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Recovery Collaborative Group, Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., and Ustianowski, A. (2021). Dexamethasone in Hospitalized Patients with COVID-19. N. Engl. J. Med., 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"},{"key":"ref_13","first-page":"m3379","article-title":"A living WHO guideline on drugs for covid-19","volume":"370","author":"Rochwerg","year":"2020","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1001\/jama.2020.17023","article-title":"Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis","volume":"324","author":"Sterne","year":"2020","journal-title":"JAMA"},{"key":"ref_15","unstructured":"National Institutes of Health (2022, April 02). COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fmed.2020.00170","article-title":"Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature","volume":"7","author":"Veronese","year":"2020","journal-title":"Front. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"593179","DOI":"10.3389\/fendo.2020.593179","article-title":"The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection","volume":"11","author":"Mao","year":"2020","journal-title":"Front. Endocrinol"},{"key":"ref_18","first-page":"83","article-title":"The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis","volume":"27","author":"Alzahrani","year":"2021","journal-title":"Endocr Pr. Off. J. Am. Coll Endocrinol Am. Assoc. Clin. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1210\/clinem\/dgaa874","article-title":"New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?","volume":"106","author":"Edwards","year":"2021","journal-title":"J. Clin. Endocrinol Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11154-021-09670-0","article-title":"Endocrine risk factors for COVID-19: Endogenous and exogenous glucocorticoid excess","volume":"23","author":"Vogel","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pinz\u00f3n, M.A., Ortiz, S., Holgu\u00edn, H., Betancur, J.F., Cardona Arango, D., Laniado, H., Arias, C.A., Mu\u00f1oz, B., Quiceno, J., and Jaramillo, D. (2021). Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252057"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ranjbar, K., Moghadami, M., Mirahmadizadeh, A., Fallahi, M.J., Khaloo, V., Shahriarirad, R., Erfani, A., Khodamoradi, Z., and Saadi, M. (2021). Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: A triple-blinded randomized controlled trial. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06045-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41591-021-01643-9","article-title":"A guide to immunotherapy for COVID-19","volume":"28","author":"Pickkers","year":"2022","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2100224","DOI":"10.1183\/13993003.00224-2021","article-title":"Corticosteroids in COVID-19: One size does not fit all","volume":"57","author":"Gogali","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.7150\/ijbs.58695","article-title":"Glucocorticoids are double-edged sword in the treatment of COVID-19 and cancers","volume":"17","author":"Yang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, J., Liao, X., Zhou, Y., Wang, L., Yang, H., Zhang, W., Zhang, Z., and Kang, Y. (2021). Association between glucocorticoids treatment and viral clearance delay in patients with COVID-19: A systematic review and meta-analysis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06548-z"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s40618-020-01325-2","article-title":"Systemic steroids in patients with COVID-19: Pros and contras, an endocrinological point of view","volume":"44","author":"Berton","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"n1380","DOI":"10.1136\/bmj.n1380","article-title":"Glucocorticoid induced adrenal insufficiency","volume":"374","author":"Prete","year":"2021","journal-title":"BMJ"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1210\/jc.2015-1218","article-title":"Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis","volume":"100","author":"Broersen","year":"2015","journal-title":"J. Clin. Endocrinol Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R111","DOI":"10.1530\/EJE-20-1199","article-title":"Management of endocrine disease: Glucocorticoid-induced adrenal insufficiency: Replace while we wait for evidence?","volume":"184","author":"Laugesen","year":"2021","journal-title":"Eur J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1001\/jama.283.8.1038","article-title":"A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin","volume":"283","author":"Annane","year":"2000","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1007\/s00134-017-4914-x","article-title":"Critical illness-related corticosteroid insufficiency (CIRCI): A narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)","volume":"43","author":"Annane","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1007\/s00134-017-4919-5","article-title":"Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017","volume":"43","author":"Annane","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1210\/clinem\/dgac201","article-title":"Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be","volume":"107","author":"Gunst","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wong, D.W.L., Klinkhammer, B.M., Djudjaj, S., Villwock, S., Timm, M.C., Buhl, E.M., Wucherpfennig, S., Cacchi, C., Braunschweig, T., and Knuchel-Clarke, R. (2021). Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19. Patients Cells, 10.","DOI":"10.1101\/2021.06.03.21258241"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.4269\/ajtmh.20-0787","article-title":"Case Report: Adrenal Pathology Findings in Severe COVID-19: An Autopsy Study","volume":"103","author":"Santana","year":"2020","journal-title":"Am. J. Trop Med. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1016\/S2666-5247(20)30115-4","article-title":"Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: A post-mortem study","volume":"1","author":"Hanley","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.5858\/arpa.2020-0248-LE","article-title":"Adrenal Vascular Changes in COVID-19 Autopsies","volume":"144","author":"Iuga","year":"2020","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Salzano, C., Saracino, G., and Cardillo, G. (2021). Possible Adrenal Involvement in Long COVID Syndrome. Medicina, 57.","DOI":"10.3390\/medicina57101087"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s40618-020-01486-0","article-title":"Relationship between betacoronaviruses and the endocrine system: A new key to understand the COVID-19 pandemic\u2014A comprehensive review","volume":"44","author":"Piticchio","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s40618-020-01311-8","article-title":"Endocrine complications of COVID-19: What happens to the thyroid and adrenal glands?","volume":"43","author":"Bellastella","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s00330-020-07226-5","article-title":"Acute adrenal infarction as an incidental CT finding and a potential prognosis factor in severe SARS-CoV-2 infection: A retrospective cohort analysis on 219 patients","volume":"31","author":"Leyendecker","year":"2021","journal-title":"Eur. Radiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Machado, I.F.R., Menezes, I.Q., Figueiredo, S.R., Coelho, F.M.A., Terrabuio, D.R.B., Ramos, D.V., Fagundes, G., Maciel, A., Latronico, A., and Fragoso, M. (2021). Primary adrenal insufficiency due to bilateral adrenal infarction in COVID-19: A case report. J. Clin. Endocrinol. Metab., dgab557.","DOI":"10.1210\/clinem\/dgab557"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/00005792-200303000-00005","article-title":"Adrenal involvement in the antiphospholipid syndrome: Clinical and immunologic characteristics of 86 patients","volume":"82","author":"Espinosa","year":"2003","journal-title":"Medicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1530\/eje.1.02002","article-title":"Acute adrenal failure as the heralding symptom of primary antiphospholipid syndrome: Report of a case and review of the literature","volume":"153","author":"Presotto","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1210\/jc.2012-4300","article-title":"Primary Adrenal Insufficiency Due to Bilateral Adrenal Hemorrhage-Adrenal Infarction in the Antiphospholipid Syndrome: Long-Term Outcome of 16 Patients","volume":"98","author":"Ramon","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2271514","DOI":"10.1155\/2021\/2271514","article-title":"Adrenal Insufficiency in Coronavirus Disease 2019 (COVID-19)-Infected Patients without Preexisting Adrenal Diseases: A Systematic Literature Review","volume":"2021","author":"Vakhshoori","year":"2021","journal-title":"Int. J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/BF03347786","article-title":"Bilateral massive adrenal hemorrhage due to sepsis: Report of two cases","volume":"17","author":"Piccioli","year":"1994","journal-title":"J. Endocrinol. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1097\/01.CCM.0000171183.79525.6B","article-title":"Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis","volume":"33","author":"Chien","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s40618-020-01276-8","article-title":"COVID-19 and the endocrine system: Exploring the unexplored","volume":"43","author":"Pal","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/s41379-021-00793-y","article-title":"Pathophysiology of SARS-CoV-2: The Mount Sinai COVID-19 autopsy experience","volume":"34","author":"Bryce","year":"2021","journal-title":"Mod. Pathol Off. J. United States Can. Acad Pathol Inc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12020-020-02325-1","article-title":"COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications","volume":"68","author":"Pal","year":"2020","journal-title":"Endocrine"},{"key":"ref_53","first-page":"E784","article-title":"Adrenal insufficiency in the COVID-19 era","volume":"320","author":"Siejka","year":"2021","journal-title":"Am. J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1365-2265.2005.02325.x","article-title":"Hypocortisolism in survivors of severe acute respiratory syndrome (SARS)","volume":"63","author":"Leow","year":"2005","journal-title":"Clin. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41593-020-00771-8","article-title":"The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice","volume":"24","author":"Rhea","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1139\/O10-022","article-title":"Endocrine cells of the adenohypophysis in severe acute respiratory syndrome (SARS)","volume":"88","author":"Wei","year":"2010","journal-title":"Biochem. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.mehy.2004.04.009","article-title":"Molecular mimicry of ACTH in SARS\u2014Implications for corticosteroid treatment and prophylaxis","volume":"63","author":"Wheatland","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1210\/edrv-10-1-92","article-title":"The immune-hypothalamic-pituitary-adrenal axis","volume":"10","author":"Bateman","year":"1989","journal-title":"Endocr. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0002-9343(99)80373-8","article-title":"Adrenal insufficiency occurring during septic shock: Incidence, outcome, and relationship to peripheral cytokine levels","volume":"98","author":"Soni","year":"1995","journal-title":"Am. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1210\/endo-125-6-3084","article-title":"Tumor necrosis factor and interleukin-1 are potent inhibitors of angiotensin-II-induced aldosterone synthesis","volume":"125","author":"Natarajan","year":"1989","journal-title":"Endocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/modpathol.2008.98","article-title":"Adrenal gland hemorrhage in patients with fatal bacterial infections","volume":"21","author":"Guarner","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Vassiliadi, D.A., Vassiliou, A.G., Ilias, I., Tsagarakis, S., Kotanidou, A., and Dimopoulou, I. (2021). Pituitary\u2014Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111473"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41420-021-00429-9","article-title":"Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients","volume":"7","author":"Awasthi","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_64","first-page":"481","article-title":"Reduced cortisol metabolism during critical illness","volume":"369","author":"Boonen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.tem.2008.01.009","article-title":"Dissociation of ACTH and glucocorticoids","volume":"19","author":"Bornstein","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4280691","DOI":"10.1155\/2022\/4280691","article-title":"Changes in Physiological Levels of Cortisol and Adrenocorticotropic Hormone upon Hospitalization Can Predict SARS-CoV-2 Mortality: A Cohort Study","volume":"2022","author":"Ahmadi","year":"2022","journal-title":"Int. J. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S2213-8587(20)30216-3","article-title":"Association between high serum total cortisol concentrations and mortality from COVID-19","volume":"8","author":"Tan","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1590\/1516-3180.2020.0722.r1.2302021","article-title":"Could serum total cortisol level at admission predict mortality due to coronavirus disease 2019 in the intensive care unit? A prospective study","volume":"139","year":"2021","journal-title":"Sao Paulo Med. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"645787","DOI":"10.3389\/fendo.2021.645787","article-title":"Spectrum of Endocrine Dysfunction and Association with Disease Severity in Patients with COVID-19: Insights From a Cross-Sectional, Observational Study","volume":"12","author":"Das","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1210\/clinem\/dgab349","article-title":"Normal Adrenal and Thyroid Function in Patients Who Survive COVID-19 Infection","volume":"106","author":"Clarke","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/jmv.27296","article-title":"Corticosteroids for COVID-19 symptoms and quality of life at 1 year from admission","volume":"94","author":"Gimeno","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"705214","DOI":"10.3389\/fendo.2021.705214","article-title":"Management of Patients with Glucocorticoid-Related Diseases and COVID-19","volume":"12","author":"Chifu","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5507\/bp.2021.011","article-title":"COVID-19, adrenal gland, glucocorticoids, and adrenal insufficiency","volume":"165","author":"Akbas","year":"2021","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czechoslov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3803\/EnM.2020.35.2.197","article-title":"Encountering COVID-19 as Endocrinologists","volume":"35","author":"Rhee","year":"2020","journal-title":"Endocrinol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s11154-020-09569-2","article-title":"Endocrine and metabolic aspects of the COVID-19 pandemic","volume":"21","author":"Marazuela","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.dsx.2020.05.050","article-title":"Managing common endocrine disorders amid COVID-19 pandemic","volume":"14","author":"Pal","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1210\/clinem\/dgz006","article-title":"Increased Infection Risk in Addison\u2019s Disease and Congenital Adrenal Hyperplasia","volume":"105","author":"Tresoldi","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1530\/EJE-12-0879","article-title":"Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: A cohort study","volume":"168","author":"Smans","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2042018819848218","DOI":"10.1177\/2042018819848218","article-title":"Adrenal crisis: Prevention and management in adult patients","volume":"10","author":"Dineen","year":"2019","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S2213-8587(17)30398-4","article-title":"Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): A single-blind, randomised controlled trial","volume":"6","author":"Isidori","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"805647","DOI":"10.3389\/fendo.2021.805647","article-title":"Frequently Asked Questions in Patients with Adrenal Insufficiency in the Time of COVID-19","volume":"12","author":"Sabbadin","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e1354","DOI":"10.1210\/clinem\/dgaa793","article-title":"Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center","volume":"106","author":"Carosi","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s40618-020-01422-2","article-title":"Impact of COVID-19 pandemic on psychophysical stress in patients with adrenal insufficiency: The CORTI-COVID study","volume":"44","author":"Martino","year":"2021","journal-title":"J. Endocrinol Invest."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11102-020-01106-3","article-title":"The direct and indirect impact of the COVID-19 pandemic on the care of patients with pituitary disease: A cross sectional study","volume":"24","author":"Graf","year":"2021","journal-title":"Pituitary"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e2469","DOI":"10.1210\/clinem\/dgab334","article-title":"The Impact of the COVID-19 Pandemic on Self-Reported Outcomes in Patients with Adrenal Insufficiency","volume":"106","author":"Li","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1210\/clinem\/dgaa148","article-title":"Our Response to COVID-19 as Endocrinologists and Diabetologists","volume":"105","author":"Kaiser","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11102-021-01130-x","article-title":"Glucocorticoid use in patients with adrenal insufficiency following administration of the COVID-19 vaccine: A pituitary society statement","volume":"24","author":"Katznelson","year":"2021","journal-title":"Pituitary"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s11154-020-09598-x","article-title":"Glucocorticoid excess and COVID-19 disease","volume":"22","author":"Guarnotta","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"711612","DOI":"10.3389\/fendo.2021.711612","article-title":"Old Problem, New Concerns: Hypercortisolemia in the Time of COVID-19","volume":"12","author":"Sworczak","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S2213-8587(20)30215-1","article-title":"COVID-19 and Cushing\u2019s syndrome: Recommendations for a special population with endogenous glucocorticoid excess","volume":"8","author":"Pivonello","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s40618-020-01419-x","article-title":"COVID-19 in Cushing disease: Experience of a single tertiary centre in Lombardy","volume":"44","author":"Serban","year":"2021","journal-title":"J. Endocrinol. Invest."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3389\/fendo.2020.00554","article-title":"Practical Considerations for the Management of Cushing\u2019s Disease and COVID-19: A Case Report","volume":"11","author":"Beretta","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1507\/endocrj.EJ20-0613","article-title":"Successful management of a patient with active Cushing\u2019s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia","volume":"68","author":"Yuno","year":"2021","journal-title":"Endocr. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12020-021-02674-5","article-title":"Clinical course and outcome of patients with ACTH-dependent Cushing\u2019s syndrome infected with novel coronavirus disease-19 (COVID-19): Case presentations","volume":"72","author":"Belaya","year":"2021","journal-title":"Endocrine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e2022","DOI":"10.6061\/clinics\/2020\/e2022","article-title":"Adrenal Insufficiency and Glucocorticoid Use During the COVID-19 Pandemic","volume":"75","author":"Almeida","year":"2020","journal-title":"Clinics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:28Z","timestamp":1760139688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":95,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137326"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137326","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}