Pituitary–Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19

Vassiliadi, Dimitra Argyro; Vassiliou, Alice G.; Ilias, Ιoannis; Tsagarakis, Stylianos; Κοτανίδου, Αναστασία; Dimopoulou, Ioanna

doi:10.3390/ijms222111473

Cited by 10 publications

(13 citation statements)

References 87 publications

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“…DHEAS has an immunostimulatory effect. DHEA is more sensitive to HPA axis stimulation than cortisol [ 20 , 21 ]. However, its relationship with the severity of COVID-19 has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity

et al. 2022

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Purpose This study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group. Methods Morning serum Aldosterone, 11-deoxycortisol, Androstenedione, 17-hydroxyprogesterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), Corticosterone, Dehydroepiandrosterone sulfate (DHEAS), Estrone, Estradiol, Progesterone, 11-deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17-hydroxypregnenolone and 21-deoxycortisol levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS). Results In our study, nearly all steroids were statistically significantly higher in the patients’ group than in the control group ( p < 0.001). Also, DHEA was an independent indicator of the disease severity with COVID-19 Conclusions Our study reveals that the alteration in steroid hormone levels was correlated with disease severity. Also, steroid hormone levels should be followed up during COVID-19 disease management.

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Section: Discussionmentioning

confidence: 99%

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity

et al. 2022

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“…DHEAS has immunostimulatory effect. DHEA has been found to be more sensitive to HPA axis stimulation than cortisol [20,21]. However, its relationship with the severity of COVID-19 has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Patients With Altered Steroid Hormone Levels Are More Likely To Have Higher Disease Severity

Sezer¹,

Bal²,

Kalem³

et al. 2022

Preprint

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Purpose: This study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group.Methods: Morning plasma Aldosterone, 11-deoxycortisol, Androstenedione, 17- hydroxyprogesterone, Dihydrotestosterone (DHT), Dihydroepiandrostenedion (DHEA), Corticosterone, Dihydroepiandrostenedion sulfate (DHEAS), Estrone, 11- deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17- hydroxypregnenolone levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS). Results: In our study, all of the steroids except DHT and DHEAS were statistically significantly higher in the patients’ group than in the control group (p>0.001). Also, DHEA was an independent predictor of the disease severity with COVID-19Conclusions: Our study reveals that altered steroid hormone levels have a negative impact on COVID-19 prognosis by simultaneous measurement of steroid hormones levels with LC-MS/MS. Also, adrenal insufficiency due to COVID-19 is an endocrinological pathology that should be followed up.

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“…The immunological, metabolic, and hemodynamic actions of glucocorticoids are mediated by a ubiquitous intracellular receptor, the GR [62]. The GR-cortisol complex translocates from the cytosol to the nucleus, where it exerts transcriptional activity, resulting in the inhibition of the inflammatory response.…”

Section: Resistance To Cortisol Action At the Level Of Glucocorticoid...mentioning

confidence: 99%

“…The GR-cortisol complex translocates from the cytosol to the nucleus, where it exerts transcriptional activity, resulting in the inhibition of the inflammatory response. Preclinical septic models have reported glucocorticoid resistance in critical illness [62]. Glucocorticoid resistance may be a consequence of decreased GR mRNA and protein expression, reduced GR affinity for the ligand and nuclear translocation, and/or impaired DNA binding.…”

Section: Resistance To Cortisol Action At the Level Of Glucocorticoid...mentioning

confidence: 99%

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

Jensterle

Herman

Almahmeed³

et al. 2022

IJMS

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Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (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.

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Pituitary–Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19

Cited by 10 publications

References 87 publications

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity

COVID-19 Patients With Altered Steroid Hormone Levels Are More Likely To Have Higher Disease Severity

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

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