Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized...

Hypothalamic-pituitary-adrenocortical (H-P-A) function was tested in 14 hyperandrogenized women, aged 17 to 32 years, who had been continuously treated with nightly single-dose oral dexamethasone, 0.25 to 1.00 mg, for 3.7 to 16.5 months. Daily AM serum cortisol concentrations were measured in nine subjects after discontinuation of dexamethasone. Basal cortisol concentrations returned to normal (greater than or equal to 6.0 micrograms/dl) within 36 hours in 67%, within 60 hours in 89%, and within 84 hours in 100%. Median time to return to normal was between 12 and 36 hours. Rate of return correlated with both the dose-adjusted duration of dexamethasone therapy (p less than 0.01) and the degree of adrenocortical suppression during treatment (p less than 0.01). The H-P-A response to insulin-induced hypoglycemia and the adrenal response to an acute intravenous adrenocorticotropic hormone (ACTH) challenge were evaluated in eight subjects 12 to 36 hours after the final dexamethasone dose. Thirty-eight percent demonstrated normal cortisol increments to hypoglycemia, 25% had blunted or absent cortisol responses to hypoglycemia but normal cortisol increments to exogenous ACTH, and 38% had blunted or absent responses to both hypoglycemia and exogenous ACTH. The responsiveness of the H-P-A axis correlated with the degree of adrenocortical suppression (p less than 0.05) but not with dose of dexamethasone or duration of treatment. Small doses of dexamethasone are not necessarily "physiologic", but dexamethasone therapy with maintenance of serum cortisol levels greater than or equal to 2.0 micrograms/dl was associated with rapid return to normal basal cortisol concentration and a normal cortisol response to insulin-induced hypoglycemia.