Impaired adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases who relapse upon tapering of low glucocorticoid dose

Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study

“…11 Notably, the reduced adrenal response was independent of age and disease duration or the duration of prior treatment with glucocorticoids, pointing to the presence of a relative adrenal insufficiency in these patients. 11 Although current evidence on underlying mechanisms of adrenocortical dysfunction in some patients with RA, coined as the 'disproportion principle', 12 13 remains inconclusive, contributing factors may include chronic stress and chronic inflammation. 13 14 Diurnal cortisol production displays a circadian rhythm in healthy individuals, with the highest levels in the morning and a gradual decline throughout the day, reaching the lowest levels around midnight.…”

“…In these particular patients, we found that both baseline cortisol levels and time-integrated cortisol responses to tetracosactide stimulation (Synacthen test) were lower compared with healthy controls, despite the absence of established adrenal insufficiency. 11 Notably, the reduced adrenal response was independent of age and disease duration or the duration of prior treatment with glucocorticoids, pointing to the presence of a relative adrenal insufficiency in these patients. 11 Although current evidence on underlying mechanisms of adrenocortical dysfunction in some patients with RA, coined as the ‘disproportion principle’, 12 13 remains inconclusive, contributing factors may include chronic stress and chronic inflammation.…”

“…Taken together, the documented efficacy of complementary low-dose prednisone may be related to our findings of an impaired adrenal reserve in patients with RA described here and supports the addition of glucocorticoids in RA treatment regimens, as a potential ‘replacement’ therapy. 11 58 …”

Protracted stress-induced hypocortisolemia may account for the clinical and immune manifestations of Long COVID

“…We suggest that Long COVID, as well as other post-viral infection sickness syndromes or sickness syndromes associated with chronic inflammatory diseases in predisposed individuals [ 25 , 26 ], are characterized by suppressed responsiveness of the HPA axis. The protracted subsequent lack of axis recovery due to a post-illness state of hypocortisolism in these individuals may be the underlying pathophysiologic mechanism responsible for, at least, some of sickness syndrome manifestations and the immune perturbations seen in Long COVID ( Fig.…”

“…Why some people are more prone to develop Long COVID, and whether HPA axis stimulants or exogenously administered glucocorticoids could have a role in the management of some of these individuals, warrant further investigation. Predisposed individuals may be those with an intrinsically compromised adrenal reserve that fails to compensate for intense or long standing increased stress [ 26 ], as seen in patients with immune-mediated and inflammatory diseases, such as rheumatoid arthritis [ 25 , 26 ].…”