Suppression of the hypothalamic-pituitary-adrenal axis after oral hydrocortisone succinate ingestion in rats

Groups of Holtzman female rats were fed 10 mg/day of hydrocortisone succinate orally to study the responsiveness of the hypothalamic-pituitary-adrenal axis to acute stress. Pituitary ACTH content, plasma ACTH, adrenal venous corticosterone, and adrenal weights were studied simultaneously in experimental and control rats before, during, and up to two weeks after oral hydrocortisone administration. There was a significant decrease in pituitary ACTH content (p=<0.001), suppression of plasma ACTH and corticosterone in response to acute stress (p=<0.001), and adrenal atrophy during and following oral hydrocortisone administration. After discontinuing the hydrocortisone it required three to five days for the rats to respond adequately to acute stress. However, it was seven to ten days post-hydrocortisone before plasma ACTH and corticosterone responses to acute stress had returned to basal values, but decreased pituitary ACTH content and partial adrenal atrophy continued throughout the ten-day post-hydrocortisone study interval. Recovering from the suppressive effects of oral hydrocortisone was more rapid than following parenteral hydrocortisone. However, oral hydrocortisone causes identical but less sustained suppression of the hypothalamic-pituitary-adrenal axis as observed in animals treated with parenteral glucocorticoid preparations.