Optimised glucocorticoid therapy: the sharpening of an old spear

Glucocorticoids are frequently and successfully used drugs that mediate important immunosuppressive and anti-inflammatory effects. These drugs are also relatively inexpensive, but it is their broad range of adverse reactions that continuously stimulate efforts to optimise glucocorticoid treatment.

Last year, Mary Leonard and colleagues studied 60 children and adolescents with nephrotic syndrome intermittently treated with high-dose glucocorticoids (N Engl J Med 2004; 351: 868-75). The patients received an average of 23 g glucocorticoids and were significantly shorter, had a significantly greater body-mass index, and the prevalence of obesity was significantly higher than in controls. The expected deficits in the bone-mineral content of the spine or whole body were not seen, although this finding could be attributed to the highly increased body-mass index of many of the patients.

Glucocorticoids are urgently needed to treat a wide range of diseases in children and adults. Therefore strategies such as preferred local application or fine-tuned dose regimens have been developed over the past five decades to improve the benefit-risk ratio. However, these efforts with conventional glucocorticoid drugs seem to have almost reached their limits. A further improvement needs qualitatively new drugs, which are currently in the development pipeline, with the most promising being the nitrosoglucocorticoids (nitrosteroids) and selective glucocorticoid-receptor agonists.