Prolonged use of synthetic corticosteroid drugs increases adrenal gland inflammation

These effects are associated with decreased expression of steroidogenic proteins.

Synthetic glucocorticoids are broadly endorsed for the treatment of various provocative and autoimmune diseases, and they can likewise influence how the adrenal gland produces endogenous glucocorticoids. No doubt, patients undergoing synthetic glucocorticoid treatment can develop adrenal insufficiency, a condition characterized by diminished responsiveness of the adrenal to ACTH stimulation or stressors.

Past studies had focused on examining the prolonged effects of corticosteroid treatment on the hypothalamus and pituitary but have not looked at the direct impact that these steroids may have on the adrenal gland.

This new study tested the theory that synthetic corticosteroids cause prolong changes in the adrenal gland steroidogenic pathways that are responsible for adrenal suppression.

Scientists found that the rhythms of glucocorticoid secretions are disrupted following prolonged treatment with synthetic corticosteroid drugs and that the adrenal steroidogenic pathway is directly influenced. Significantly, these progressions continue long after the end of the procedure.

Scientists also showed a pro-inflammatory effect of synthetic glucocorticoid treatment in the adrenal gland. This is a significant finding with high clinical pertinence as intra-adrenal activation of the immune system can affect adrenal functionality by meddling with the steroidogenic pathway, harming adrenal endothelial microvascular cells, and by instigating apoptosis and decreasing cell viability.

Dr. Francesca Spiga, Honorary Research Fellow in the Bristol Medical School: Translational Health Sciences (THS) and corresponding author, said“Our study provides valuable insights on the regulation of the adrenal steroidogenic pathway that are important starting points for future studies on adrenal gland physiology.

“Importantly, our research builds on our knowledge of the mechanisms through which corticosteroid drugs induce adrenal insufficiency, by showing simultaneous effects within multiple pathways involved in steroidogenesis, including circadian clock genes and inflammation pathways.”

“A more detailed understanding of the effects of synthetic glucocorticoids on glucocorticoid hormone’s dynamics and adrenal steroidogenic activity and the identification of mechanisms regulating these effects will help develop better treatments that will improve patient care.”

Future studies should address whether adrenal insufficiency and its effects, can be prevented by using synthetic corticosteroid drugs that more closely resemble endogenous glucocorticoids in terms of effectiveness and plasma half-life.

Journal Reference:
  1. Francesca Spiga. Prolonged treatment with the synthetic glucocorticoid methylprednisolone affects adrenal steroidogenic function and response to inflammatory stress in the rat. DOI: 10.1016/j.bbi.2020.03.001

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