What are the factors that play a role in the development of iatrogenic Cushing’s syndrome?

Multiple factors decide the effects of steroids and hence the development of iatrogenic Cushing’s syndrome. Steroids are available in many different preparations and have different modes of delivery. Although the use of topical, intra-articular, or aerosol therapy has the advantage of allowing more targeted therapy and therefore theoretically fewer systemic adverse effects, every mode of steroid treatment can cause Cushing’s features.

Relevant properties of the steroids themselves include the formulation used, pharmacokinetics, affinity for the glucocorticoid receptor, biologic potency, and duration of action. Pharmacokinetic factors include binding affinities to cortisol-binding globulin (CBG) and other plasma proteins, metabolic inactivation, and plasma half-life. Most synthetic glucocorticoids do not have significant binding to CBG and bind instead to albumin or circulate as free steroid. In contrast, syntheticglucocorticoids have a much higher affinity for the glucocorticoid receptor than cortisol itself. However, these are theoretical considerations and relative estimate of glucocorticoid activity and hence development of Cushing’s features cannot be predicted.

Specific modes of delivery have different effects. Oral steroid use is most common form likely to cause Cushing’s features. Topical steroids do get systemically absorbed and this may further be enhanced by breakdown of skin integrity. Inhaled glucocorticoids initially thought to be safe do have side effects particularly bone, ocular, and skin manifestations. Cushing’s syndrome has been reported in patients taking relatively high doses of intra-articular glucocorticoids. Pediatric cases of intra-articular and intradermal steroid injections causing Cushing’s syndrome have been reported.

The minimum dose of steroid required for development of Cushing’s syndrome is the equivalent of prednisolone in dose of 7.5 mg for 3 months.