Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?

Abstract

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.

Drug-Induced Atypical Lipodystrophy

“…The simultaneous use of anabolic androgen in this setting has a resemblance to pituitary Cushing, especially in younger patients, where the adrenal androgen excess (DHEAS) and increased physical activity reasonably reduce protein catabolism and may help in preserving muscle and bone mass. Recently, there has been emerging evidence of 11-β-hydroxy steroid dehydrogenase (HSD)-1's role in the clinical manifestation of Cushing syndrome [ 14 ]. Independent case reports of proven Cushing disease and adrenal Cushing without any of the discriminatory/metabolic manifestations have been reported [ 15 , 16 ].…”

Gut microbiota does not play a mediating role in the causal association between inflammatory bowel disease and several its associated extraintestinal manifestations: a Mendelian randomization study

“…Mesalazine and cyclosporine are thought to carry a risk of inducing acute pancreatitis, and cyclosporine is also thought to cause an increased incidence of cholelithiasis ( 37 , 38 ). Insulin resistance and type 2 diabetes, on the other hand, are side effects of glucocorticoid ( 39 ). Several studies have shown significantly higher rates of obesity in patients with IBD, which is also thought to cause an increased risk of developing many autoimmune diseases, including type 1 diabetes and multiple sclerosis, and vascular diseases ( 40 – 43 ).…”

Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway

“…The role of inflammation in EC dysfunction is well established [ 15 ], and ICAM-1 is widely recognized as a reliable marker indicating EC infiltration and activation [ 16 , 17 ]. Considering the numerous side effects and drug resistance associated with anti-inflammatory therapies like ketoconazole, activated protein C, and glucocorticoids [ 18 , 19 ], there is an unmet clinical need to develop safer and more effective medications for inflammation.…”