Adrenal Function in Relation to Cytokines and Outcome in Non-critically Ill Patients with COVID-19

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2023 Sep 13

PMID 37702927

Authors

N Athanasiou

A Diamantopoulos

C Keskinidou

P Katsaounou

A Angelousi

E Jahaj

P Mourelatos

C S Vrettou

E Botoula

A G Vassiliou

A Kotanidou

S Tsagarakis

I Dimopoulou

D A Vassiliadi

Affiliations

Soon will be listed here.

Abstract

Purpose: We aimed to identify whether hypothalamic-pituitary-adrenal (HPA) axis dysfunction is related to deterioration in a percentage of patients who progress to severe COVID-19.

Methods: In this cohort observational study, we evaluated HPA axis activation by measuring cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate (DHEA-S) levels, whole blood expression levels of the key glucocorticoid receptor, GCR-α, and the glucocorticoid-induced leucine zipper (GILZ), and cytokines, as markers of the inflammatory phase, in 149 patients with respiratory infection admitted in the ward, without known adrenal disease and/or confounding medications (glucocorticoids). One hundred and four (104) patients were SARS-CoV-2 positive (C +) and controls consisted of 45 SARS-CoV-2-negative patients (NC).

Results: No differences in cortisol levels were observed between the C + and the NC patients. Cortisol levels correlated with ACTH (r = 0.284, p = 0.001) and IL-6 (r = 0.289, p = 0.04). In C + patients, cortisol levels mainly correlated with IL-6 levels (r = 0.28; p = 0.017). GCR-α expression was significantly higher in C + patients compared to NC. Patients with higher cortisol levels were more likely to progress to respiratory function deterioration or die. Both GCR-α and GILZ expression were significantly higher in C + non-survivors.

Conclusion: Our findings indicate that cortisol serves as an indicator of disease severity. GILZ expression appears to be a more effective marker of mortality prediction in moderate COVID-19 cases. However, routine measurement of GILZ levels is currently unavailable. Elevated levels of cortisol may be indicative of patients with moderate COVID-19 who are at a higher risk of deterioration. This information can aid in identifying individuals who require early medical attention.

References

Wong C, Wong J, Tang E, Au C, Wai A . Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis. Sci Rep. 2020; 10(1):19765. PMC: 7666204. DOI: 10.1038/s41598-020-74988-9. View

Thakur M, Datusalia A, Kumar A . Use of steroids in COVID-19 patients: A meta-analysis. Eur J Pharmacol. 2021; 914:174579. PMC: 8525014. DOI: 10.1016/j.ejphar.2021.174579. View

Boonen E, Bornstein S, Van den Berghe G . New insights into the controversy of adrenal function during critical illness. Lancet Diabetes Endocrinol. 2015; 3(10):805-15. DOI: 10.1016/S2213-8587(15)00224-7. View

Kanczkowski W, Evert K, Stadtmuller M, Haberecker M, Laks L, Chen L . COVID-19 targets human adrenal glands. Lancet Diabetes Endocrinol. 2021; 10(1):13-16. PMC: 8601687. DOI: 10.1016/S2213-8587(21)00291-6. View

Quatrini L, Ugolini S . New insights into the cell- and tissue-specificity of glucocorticoid actions. Cell Mol Immunol. 2020; 18(2):269-278. PMC: 7456664. DOI: 10.1038/s41423-020-00526-2. View

Marik P, Pastores S, Annane D, Meduri G, Sprung C, Arlt W . Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008; 36(6):1937-49. DOI: 10.1097/CCM.0b013e31817603ba. View

Tan T, Khoo B, Mills E, Phylactou M, Patel B, Eng P . Association between high serum total cortisol concentrations and mortality from COVID-19. Lancet Diabetes Endocrinol. 2020; 8(8):659-660. PMC: 7302794. DOI: 10.1016/S2213-8587(20)30216-3. View

Guven M, Gultekin H . Could serum total cortisol level at admission predict mortality due to coronavirus disease 2019 in the intensive care unit? A prospective study. Sao Paulo Med J. 2021; 139(4):398-404. PMC: 9615598. DOI: 10.1590/1516-3180.2020.0722.R1.2302021. View

Bornstein S, Engeland W, Ehrhart-Bornstein M, Herman J . Dissociation of ACTH and glucocorticoids. Trends Endocrinol Metab. 2008; 19(5):175-80. DOI: 10.1016/j.tem.2008.01.009. View

10.

Alzahrani A, Mukhtar N, Aljomaiah A, Aljamei H, Bakhsh A, Alsudani N . The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis. Endocr Pract. 2021; 27(2):83-89. PMC: 7837186. DOI: 10.1016/j.eprac.2020.10.014. View