Management of Patients With Glucocorticoid-Related Diseases and COVID-19

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health crisis affecting millions of people worldwide. SARS-CoV-2 enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2) after being cleaved by the transmembrane protease serine 2 (TMPRSS2). In addition to the lung, gastrointestinal tract and kidney, ACE2 is also extensively expressed in endocrine tissues, including the pituitary and adrenal glands. Although glucocorticoids could play a central role as immunosuppressants during the cytokine storm, they can have both stimulating and inhibitory effects on immune response, depending on the timing of their administration and their circulating levels. Patients with adrenal insufficiency (AI) or Cushing’s syndrome (CS) are therefore vulnerable groups in relation to COVID-19. Additionally, patients with adrenocortical carcinoma (ACC) could also be more vulnerable to COVID-19 due to the immunosuppressive state caused by the cancer itself, by secreted glucocorticoids, and by anticancer treatments. This review comprehensively summarizes the current literature on susceptibility to and outcome of COVID-19 in AI, CS and ACC patients and emphasizes potential pathophysiological mechanisms of susceptibility to COVID-19 as well as the management of these patients in case of SARS-CoV-2. Finally, by performing an in silico analysis, we describe the mRNA expression of ACE2, TMPRSS2 and the genes encoding their co-receptors CTSB, CTSL and FURIN in normal adrenal and adrenocortical tumors (both adenomas and carcinomas).

Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing’s Syndrome: A Case Report and Review of Literature

“…We ourselves have treated a severely obese female patient with active CD on pasireotide, who developed ARDS despite addition of high doses of methylprednisolone (unpublished data). Additional risk imposed by comorbidities cannot be underestimated ( 15 , 16 ). This is particularly relevant for obesity, that not only hampers immune system (leading to increased levels of IL-1, IL-6, and TNF-α), but adipocytes represent a reservoir of SARS-CoV-2 thanks to ACE2 receptor, crucial for virus attachment ( 15 ).…”

“…While some of these drugs demonstrate quick onset of action regarding normalization of cortisol level (and hence improve clinical comorbidities), rapid effects on immune system responses are not likely, which might be of great relevance in case of acute infection. Secondly, adrenolytic therapy increases a risk of AI, which can be even more perilous than CS in case of infection or other stress situations ( 8 , 12 , 15 , 16 ). A modified “block and replace” approach may be considered, where addition of hydrocortisone could diminish the risk of AI ( 7 ).…”

The Relationship between COVID-19 and Hypothalamic–Pituitary–Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess—The CAPISCO International Expert Panel

“…The high degree of endocrine system involvement in COVID-19 quickly indicated the clinical relevance of pre-existing endocrine disorders [1]. Both impaired cortisol secretion and excess, as observed with AI and Cushing's syndrome, may increase susceptibility to SARS-CoV-2 infection and the risk of severe forms of COVID-19 and therefore position those patients in potentially vulnerable groups [72]. As well as defined adrenal disorders, long-term glucocorticoid treatment should be considered the most common cause of adrenal dysfunction in the general population [73].…”

“…In order to accommodate for the insufficient serum cortisol increase during infection, AI patients are advised to follow the "sick day rules" immediately when the first symptoms might appear by a self-adjusted rise in hydrocortisone dose administration. They are encouraged to contact their referral endocrinologist and continue with doubled or tripled daily oral glucocorticoid doses in relation to the severity of COVID-19 symptoms until the symptoms resolve [1,72,74,81]. Hospital admission and treatment with parenteral glucocorticoids are recommended in the case of clinical deterioration or if the patients experience vomiting or diarrhea [74,86].…”

“…Hypercortisolemia induces persistent low-grade inflammation and immunosuppression with a hampered innate immune response and lowered activation of adaptive immune mechanisms. Indeed, patients with exogenous or endogenous glucocorticoid excess have increased susceptibility to infections and frequently experience a more severe and protracted clinical course of respiratory viral infections and other various fungal, bacterial, and viral infections [72,88]. In addition, multiple comorbidities known to increase COVID-19 severity such as impaired glucose metabolism, arterial hypertension, obesity, and hypercoagulability are overrepresented in these patients and commonly persist despite the remission of the primary disease [88,89].…”