Glucocorticoid withdrawal syndrome: what to expect and how to manage

Glucocorticoid withdrawal syndrome (GWS) can develop after withdrawing exposure to supraphysiological levels of endogenous or exogenous glucocorticoids due to an established physical dependence. It is characterised by symptoms similar to adrenal insufficiency but needs to be regarded as a separate entity. GWS is often under-recognised in clinical practice and affected patients can experience significant impairment in their quality of life.

A cornerstone in GWS management is adequate patient education and reassurance that symptoms are expected and typically temporary. Patients with endogenous Cushing's syndrome need to be aware that psychopathology may persist into the postoperative period. GWS is more likely to develop in severe Cushing's syndrome and in patients with very low levels of cortisol after surgery. Postoperatively, glucocorticoid replacement should be initiated and tapered in an individualised approach but there is currently no consensus on the best tapering strategy. If symptoms of GWS develop, glucocorticoid replacement ought to be temporarily increased to the previous, well tolerated dose. No randomised studies have thus far compared regimens for withdrawing glucocorticoids after treatment for anti-inflammatory or immunosuppressive causes to determine the best and safest tapering strategy. One open-label, single-arm trial in patients with asthma has recently proposed a personalised glucocorticoid tapering regimen which included the systematic assessment of adrenal function.

Awareness of GWS by treating physicians and patient education are essential. Evidence on optimal GWS management after Cushing's syndrome treatment is scarce, but new data are emerging for tapering after long-term glucocorticoid treatment.