Rapid hypothalamic-pituitary recovery after chronic glucocorticoid therapy enables strategies that prevent adrenal suppression.

ABSTRACT: Glucocorticoid-induced adrenal insufficiency (GIAI) persists for months to years after long-term treatment, which past studies suggest is mediated by initial, post-withdrawal hypothalamic-pituitary suppression. We examined the timing of hypothalamic, pituitary, and adrenal (HPA) recovery after 8 weeks of dexamethasone (DEX) treatment in mice. At withdrawal, HPA function was fully suppressed, but Crh mRNA and plasma ACTH surprisingly rebounded above control levels within 1 week. Despite this, corticosterone (CORT) remained suppressed for an additional 7 weeks. DEX-exposed adrenals were atrophic and contained previously undescribed, giant, multinucleated histiocytes. CORT secretion was disproportionately low relative to the non-histocyte adrenocortical area in the first 1-2 weeks post

SUBMITTER: Gaston LS 

PROVIDER: S-EPMC12247942 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature