Adrenal Insufficiency in Coronavirus Disease 2019

A Case Report

Maryam Heidarpour; Mehrbod Vakhshoori; Saeed Abbasi; Davood Shafie; Nima Rezaei


J Med Case Reports. 2020;14(134) 

In This Article

Discussion and Conclusions

This current report presented an individual infected with COVID-19 with no prior history of adrenal diseases who experienced acute adrenal insufficiency during hospitalization. Due to the new emergence of this virulent pathogen, which mostly affects the respiratory system, other non-respiratory presentations of this infection must be considered, especially in terms of endocrine organs. Adrenal insufficiency seems to be a common problem observed among critically ill patients. It has been reported that patients suffering from severe cases of sepsis, burns, pancreatitis, head trauma, cardiac surgery, or liver disease might experience this disorder. Because of variable definitions and different study populations, the exact incidence of adrenal insufficiency remains unknown.[4] Several mechanisms have been suggested for the development of this disease, including cancer, hemorrhages, thrombosis, autoimmune issues, and drugs, as well as infections leading to sepsis. These aforementioned circumstances may increase cortisol demand, which can result in adrenal insufficiency occurrence.

Moreover, an imbalance between the endocrine system and the immune system might play a role in this regard.[4] The enormous production of inflammatory markers, including interleukin (IL) 1, IL-6, and tumor necrosis factor α (TNF-α), has been suggested to influence the hypothalamic–pituitary–adrenal (HPA) axis because of non-protection of the pituitary gland by the blood–brain barrier. Furthermore, TNF-α leads to decreased adrenocorticotropic hormone (ACTH) release induced by corticotrophin-releasing hormone (CRH) and impairs the function of ACTH and angiotensin 2 on adrenal cells.[7–9] The cytokine storm that resulted from systemic infection caused by COVID-19 might be responsible for the development of adrenal insufficiency. On the other hand, the essential substrate for cortisol production is cholesterol, which is mainly in the form of high-density lipoprotein (HDL). A decrease in HDL level, observed more frequently in severe illnesses, could be considered another possible etiology of adrenal insufficiency.[10] Also, a term named "critical illness-related corticosteroid insufficiency" (CIRCI) has been announced recently. This functional relative adrenal insufficiency is not strictly dependent on cortisol level for diagnosis, but mostly relies on the inadequacy of cortisol for inflammation control or supplying raised metabolic demand.[11] Decreased levels of cortisol carrier proteins, including cortisol-binding globulins (CBGs) or albumin, reduced cortisol-CBG complex cleavage, increased activity of an enzyme responsible for inactivation of cortisol (11-β hydroxysteroid dehydrogenase type 2), as well as decreased numbers of cortisol receptors and affinity have been postulated to be effective in the pathogenesis of this functional syndrome. Overall, because physiological concentrations of corticosteroids play a crucial role in maintaining an appropriate vascular response to vasoconstrictors, adrenal insufficiency was associated with severe resistant hypotension, which was entirely reversed with corticosteroids.[5] On the other hand, it has been suggested that an older member of the Coronaviridae family, named severe acute respiratory syndrome (SARS), produces certain amino acid sequences mimicking host ACTH. Consequently, antibody production against this peptide might be responsible for the occurrence of adrenal insufficiency.[12] Moreover, the hypothalamus and pituitary express angiotensin-converting enzyme 2 (ACE2) and SARS genome had been identified in autopsy samples. Therefore, this new coronavirus might also affect the HPA axis and cause acute adrenal insufficiency.[13,14]

In conclusion, adrenal insufficiency should be considered among critically ill patients infected with COVID-19, and high clinical suspicion is required in this regard, especially during hypotensive attacks unresponsive to vasopressor agents. However, the exact etiology for the pathogenesis of this disorder needs to be investigated further.