Short-Course, Low-Dose Betamethasone Therapy Causes only Marginal and Transient Hypothalamic-Pituitary-Adrenal-Axis Suppression

Objective The aim of this study was to establish the degree of hypothalamic-pituitary-adrenal (HPA) axis suppression occurring with low oral doses of betamethasone over 5 days. Prednisolone 10mg was used as a comparator as it is considered a well tolerated short-course therapy for atopic conditions. Study Design and Participants 50 healthy adult volunteers not on cortico-steroid therapy were randomised to five treatment groups of 10 volunteers each to receive either oral betamethasone 0.25mg, 0.5mg, l.0mg or 2.0mg, or oral prednisolone 10mg. Interventions and Measurements Serum cortisol was measured in samples collected between 7am and 8am on days 1, 2, 3, 5 and 8. Tetracosactide (Synachten®, Novartis) was used in physiological concentrations (i.e. 1 mg/L intravenously) to elicit adrenal cortisol release at baseline and again on day 8 to test for drug-induced suppression. Blood samples were collected at 30 and 60 minutes to evaluate the serum cortisol response. Overnight urine was collected for the calculation of the urine cortisol: creatinine ratio on days 1, 5, 8,10,15 and 21. Results On both day 1 (baseline) and day 8 tetracosactide elicited similar increases in serum cortisol levels at 30 minutes in all five treatment groups, suggesting a normal physiological response. However, the 30-minute post-stimulation serum cortisol levels in the groups receiving betamethasone 1mg and 2mg did not reach the cited normal values, i.e. above 500 nmol/L, on day 8. Urine cortisol: creatinine ratios were significantly suppressed by betamethasone land 2mg on days 5 and 8, respectively. Serum cortisol levels were significantly reduced in all treatment groups, but returned to normal by day 8 in all groups except in the betamethasone 2mg group. The urine cortisol : creatinine ratios returned to normal by day 15 in the betamethasone 2mg group. Conclusions The extent of suppression of serum cortisol was similar with betamethasone 0.25mg, 0.5mg and lmg and prednisolone 10mg. Betamethasone 2mg had more pronounced effects on serum cortisol levels and urine cortisol: creatinine ratios. These findings, therefore, indicate mild adrenal suppression after a 5-day oral course of therapy, but with rapid recovery thereafter. This indicates a normal adrenal reserve and thus short courses of low-dose betamethasone may be considered a well tolerated treatment for atopic diseases in otherwise healthy individuals.