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

Mojca Jensterle, Rok Herman, Andrej Janež*, Wael Al Mahmeed, Khalid Al-Rasadi, Kamila Al-Alawi, Maciej Banach, Yajnavalka Banerjee, Antonio Ceriello, Mustafa Cesur, Francesco Cosentino, Massimo Galia, Su Yen Goh, Sanjay Kalra, Peter Kempler, Nader Lessan, Paulo Lotufo, Nikolaos Papanas, Ali A. Rizvi, Raul D. SantosAnca P. Stoian, Peter P. Toth, Vijay Viswanathan, Manfredi Rizzo

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding sever-ity, 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.

Original languageEnglish
Article number7326
JournalInternational Journal of Molecular Sciences
Volume23
Issue number13
DOIs
Publication statusPublished - Jul 1 2022

Keywords

  • adrenal insufficiency
  • glucocorticoids
  • hypercortisolism
  • hypothalamic–pituitary–adrenal axis
  • SARS-CoV-2

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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