Dexamethasone suppression test predicts later development of an impaired adrenal function after a 14-day course of prednisone in healthy volunteers

Abstract

Background: Suppression of the adrenal function after glucocorticoid treatment is common, potentially dangerous, and unpredictable. Identification of patients at risk is of clinical importance. We hypothesized that the dexamethasone suppression test predicts the development of corticosteroidinduced impaired adrenal function. Methods: We included 39 healthy male volunteers. After a 1-mg ACTH test, all participants underwent an overnight 0.5-mg dexamethasone suppression test. Participants then took prednisone, 0.5 mg/kg body weight, for 14-day. After the withdrawal of prednisone, a 1-mg ACTH test was performed and a clinical score was assessed on days 1, 3, 7, and 21. Results: On days 1, 3, 7, and 21, 100, 50, 26.5 and 32.4% of the participants had a suppressed adrenal function. The risk of developing suppressed adrenal function decreased from 44 to 0% in patients with cortisol levels after the administration of dexamethasone in the lowest and highest quartiles respectively. Receiver operating curve (ROC) analysis performed to predict a suppressed adrenal function on day 7 after the withdrawal of prednisone showed an area under the curve (AUC) of 0.76 (95% confidence interval (CI) 0.58-0.89) for cortisol after the administration of dexamethasone, which was in the range of the AUC of 0.78 (95% CI 0.6-0.9) for pre-intervention cortisol after the administration of ACTH. Basal cortisol before intake of prednisone (AUC 0.62 (95% CI 0.44-0.78)) and the clinical score (AUC 0.64 (95% CI 0.45-0.79)) had significantly lower AUCs. Conclusion: Circulating cortisol levels after a dexamethasone suppression test and a pre-interventionstimulated cortisol level are predictive of later development of a suppressed adrenal function after a 14-day course of prednisone, and are superior to a clinical score or basal cortisol levels. This may allow a more targeted concept for the need of stress prophylaxis after cessation of steroid therapy.

MANAGEMENT OF ENDOCRINE DISEASE: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

“…Other plausible gene loci include those coding for the glucocorticoid receptor or the enzyme 11β-HSD. The response to glucocorticoids varies considerably among individuals and this may also affect susceptibility to glucocorticoid-induced adrenal insufficiency, as demonstrated by the low-dose dexamethasone suppression test (62). At present, polymorphisms in the gene loci encoding the glucocorticoid receptor as well as 11β-HSD are leading candidate genes to account for the large variation in glucocorticoid response (63).…”

Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis

“…However, individual variation in HPA axis function after GC withdrawal can be observed and it may be caused by individual variation in sensitivity towards GCs. It has been demonstrated that the risk of suppressed adrenal function after a seven-day prednisone treatment is increased in subjects who have a low cortisol level after a dexamethasone suppression test [ 84 ]. Individual differences in GC sensitivity are important in evaluating a patient’s risk of developing GC-induced adrenal insufficiency.…”

Glucocorticoid induced adrenal insufficiency

“…Short courses (<2 weeks) of high dose glucocorticoids are usually associated with a swift recovery of adrenal function,183738 although cases of GI-AI lasting more than seven to 14 days have been described 31394041424344. The possible exception to this is in patients who receive frequent short glucocorticoid courses, as in the treatment of asthma or chronic obstructive pulmonary disease and during emetogenic chemotherapy.…”

“…Inter-individual variability in the sensitivity of the HPAA to exogenous glucocorticoids has been observed 44128129. For example, higher cortisol after administration of dexamethasone was associated with an inadequate response to the low dose ACTH stimulation test after a 14 day course of prednisolone in healthy volunteers 44.…”

“…Inter-individual variability in the sensitivity of the HPAA to exogenous glucocorticoids has been observed 44128129. For example, higher cortisol after administration of dexamethasone was associated with an inadequate response to the low dose ACTH stimulation test after a 14 day course of prednisolone in healthy volunteers 44. This variation is possibly linked—among other factors—to polymorphisms of the genes encoding the glucocorticoid and mineralocorticoid receptors 14129130131132.…”