Hypothalamic-Pituitary-Adrenal Axis Activity in SARS-CoV-2 Infected Noncritically Ill Hospitalized Patients

Hurjahan Banu; Nusrat Sultana; Md Shahed-Morshed; M A Hasanat; Ahmed Abu Saleh; Shohael Mahmud Arafat

doi:10.15605/jafes.038.02.04

Authors

Hurjahan Banu Bangabandhu Sheikh Mujib Medical University, Bangladesh https://orcid.org/0000-0002-8115-1761
Nusrat Sultana Bangabandhu Sheikh Mujib Medical University, Bangladesh https://orcid.org/0000-0002-6858-2110
Md Shahed-Morshed Kurmitola General Hospital, Bangladesh https://orcid.org/0000-0001-6115-2655
M A Hasanat Bangabandhu Sheikh Mujib Medical University, Bangladesh https://orcid.org/0000-0001-8151-9792
Ahmed Abu Saleh Bangabandhu Sheikh Mujib Medical University, Bangladesh https://orcid.org/0000-0001-7552-0674
Shohael Mahmud Arafat Bangabandhu Sheikh Mujib Medical University, Bangladesh

DOI:

https://doi.org/10.15605/jafes.038.02.04

Keywords:

Hypothalamic-Pituitary-Adrenal Axis, Cortisol, ACTH, SARS-CoV-2, Coronavirus disease 2019

Abstract

Objectives. This study determined the baseline hormonal levels of the hypothalamic-pituitary-adrenal axis and their associated factors in noncritically ill hospitalized patients with coronavirus disease 2019 (COVID-19).

Methodology. This cross-sectional observational study was carried out in 91 noncritical RT-PCR-confirmed COVID-19 patients (18-65 years) recruited consecutively from the COVID unit, of two tertiary care hospitals over a period of six months. After screening for exclusion criteria relevant history and physical examinations were done, and blood was drawn between 07:00 am to 09:00 am in a fasting state to measure serum cortisol and plasma adrenocorticotropic hormone (ACTH) by chemiluminescent microparticle immunoassay.

Result. Of 91 patients, 54, 26, and 11 had mild, moderate, and severe disease respectively. Median values of serum cortisol (p=0.057) and plasma ACTH (p=0.910) were statistically similar among the severity groups. Considering cortisol cut-off of 276 nmol/L (<10 μg/dL), the highest percent of adrenal insufficiency was present in severe (27.3%), followed by mild (25.9%) and least in moderate (3.8%) COVID-19 cases. Using the cortisol/ACTH ratio >15, only 6.6% had enough reserve.

Conclusions. The adrenocortical response was compromised in a significant percentage of noncritically ill hospitalized patients with COVID-19, which is unrelated to infection severity, with greater percentages present in severely infected cases.

Downloads

Download data is not yet available.

Author Biographies

Hurjahan Banu, Bangabandhu Sheikh Mujib Medical University, Bangladesh

Medical Officer, Department of Endocrinology

Nusrat Sultana, Bangabandhu Sheikh Mujib Medical University, Bangladesh

Assistant Professor, Department of Endocrinology

Md Shahed-Morshed, Kurmitola General Hospital, Bangladesh

Emergency Medical Officer

M A Hasanat, Bangabandhu Sheikh Mujib Medical University, Bangladesh

Professor, Department of Endocrinology

Ahmed Abu Saleh, Bangabandhu Sheikh Mujib Medical University, Bangladesh

Professor, Department of Microbiology & Immunology

Shohael Mahmud Arafat, Bangabandhu Sheikh Mujib Medical University, Bangladesh

Professor, Department of Internal Medicine

References

Téblick A, Peeters B, Langouche L, Van den Berghe G. Adrenal function and dysfunction in critically ill patients. Nat Rev Endocrinol. 2019;15(7):417–27. https://pubmed.ncbi.nlm.nih.gov/30850749. https://doi.org/10.1038/s41574-019-0185-7.

Khoo B, Boshier PR, Freethy A, et al. Redefining the stress cortisol response to surgery. Clin Endocrinol (Oxf). 2017;87(5):451–8. https://pubmed.ncbi.nlm.nih.gov/28758231. https://doi.org/10.1111/cen.13439.

Mongioì LM, Barbagallo F, Condorelli RA, et al. Possible long-term endocrine-metabolic complications in COVID-19: Lesson from the SARS model. Endocrine. 2020;68(3):467-70. https://pubmed.ncbi.nlm.nih.gov/32488837. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266418. https://doi.org/10.1007/s12020-020-02349-7.

Agarwal S, Agarwal SK. Endocrine changes in SARS-CoV-2 patients and lessons from SARS CoV. Postgrad Med J. 2020;96(1137):412-6. https://pubmed.ncbi.nlm.nih.gov/32527756. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306278. https://doi.org/10.1136/postgradmedj-2020-137934.

Chappell MC. Commentary for “Endocrine significance of SARS-CoV-2’s reliance on ACE2.” Endocrinology. 2021;162(4):bqaa222. https://pubmed.ncbi.nlm.nih.gov/33269375. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799108. https://doi.org/10.1210/endocr/bqaa222.

Garg MK, Gopalakrishnan M, Yadav P, Misra S. Endocrine involvement in COVID-19: Mechanisms, clinical features, and implications for care. Indian J Endocrinol Metab. 2020;24(5):381-6. https://pubmed.ncbi.nlm.nih.gov/33489841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810055. https://doi.org/10.4103/ijem.IJEM_440_20.

Frara S, Allora A, Castellino L, di Filippo P, Loli P, Giustina A. COVID-19 and the pituitary. Pituitary. 2021;24(3):465-81. https://pubmed.ncbi.nlm.nih.gov/33939057. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089131. https://doi.org/10.1007/s11102-021-01148-1.

Somasundaram NP, Gunatilake SSC. Infections in endocrinology: Viruses. In: Feingold KR, Anawalt B, Boyce A, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. https://pubmed.ncbi.nlm.nih.gov/33734656. Bookshelf ID: NBK568565.

Grassi T, Varotto E, Galassi FM. COVID-19, a viral endocrinological disease? Eur J Intern Med. 2020;77:156-7. https://pubmed.ncbi.nlm.nih.gov/32571582. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274643. https://doi.org/10.1016/j.ejim.2020.06.003.

RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704. https://pubmed.ncbi.nlm.nih.gov/32678530. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383595. https://doi.org/10.1056/NEJMoa2021436.

Alzahrani AS, Mukhtar N, Aljomaiah A, al. The impact of COVID-19 viral infection on the hypothalamic-pituitary-adrenal axis. Endocr Pract. 2021;27(2):83-9. https://pubmed.ncbi.nlm.nih.gov/33554871. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837186. https://doi.org/10.1016/j.eprac.2020.10.014.

World Health Organization. Clinical management of COVID-19: Interim guidance, 27 May 2020. Accessed August 2, 2022. https://apps.who.int/iris/handle/10665/332196.

Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348(8):727-34. https://pubmed.ncbi.nlm.nih.gov/12594318. https://doi.org/10.1056/NEJMra020529.

Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-247. https://pubmed.ncbi.nlm.nih.gov/34599691. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486643. https://doi.org/10.1007/s00134-021-06506-y.

Santana MF, Borba MGS, Baía-da-Silva DC, et al. Case report: Adrenal pathology findings in severe COVID-19: an autopsy study. Am J Trop Med Hyg. 2020;103(4):1604–7. https://pubmed.ncbi.nlm.nih.gov/32876012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543860. https://doi.org/10.4269/ajtmh.20-0787.

Pal R. COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications. Endocrine. 2020;68(2):251–2. https://pubmed.ncbi.nlm.nih.gov/32346813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186765. https://doi.org/10.1007/s12020-020-02325-1.

Kumar B, Gopalakrishnan M, Garg MK, et al. Endocrine dysfunction among patients with COVID-19: A single-center experience from a tertiary hospital in India. Indian J Endocrinol Metab. 2021;25(1):14-9. https://pubmed.ncbi.nlm.nih.gov/34386388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323627. https://doi.org/10.4103/ijem.IJEM_577_20.

Etoga MCE, Inna AH, Fokeng MG, et al. Baseline serum total cortisol during the primary coronavirus infection in the beginning of the COVID-19 pandemic in Cameroon. Ann Endocrinol Metab. 2021;4(1):55-60. https://doi.org/10.36959/433/567.

Wheatland R. Molecular mimicry of ACTH in SARS – Implications for corticosteroid treatment and prophylaxis. Med Hypotheses. 2004;63(5):855–62. https://pubmed.ncbi.nlm.nih.gov/15488660. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126000. https://doi.org/10.1016/j.mehy.2004.04.009.

Gu WT, Zhou F, Xie WQ, Wang S, Yao H, Liu YT, et al. A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors. Endocrine. 2021;72(2):340–8. https://pubmed.ncbi.nlm.nih.gov/33786714. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009460. https://doi.org/10.1007/s12020-021-02697-y.

Lee MK, Vasikaran S, Doery JC, Wijeratne N, Prentice D. Cortisol: ACTH ratio to test for primary hypoadrenalism: A pilot study. Postgrad Med J. 2013;89(1057):617-20. https://pubmed.ncbi.nlm.nih.gov/23729816. https://doi.org/10.1136/postgradmedj-2012-131723.

Karaca Z, Lale A, Tanriverdi F, Kula M, Unluhizarci K, Kelestimur F. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary. 2011;14(2):134-40. https://pubmed.ncbi.nlm.nih.gov/21061072. https://doi.org/10.1007/s11102-010-0270-3.