HPA Axis (Hypothalamic-Pituitary-Adrenal Axis)
The hormonal cascade linking the hypothalamus, pituitary, and adrenal glands that controls the stress response and cortisol production. Corticotropin (ACTH) acts on this axis, cosyntropin is used to test its function, and pasireotide treats its dysregulation in Cushing's disease.
Technical Context
The HPA axis cascade: hypothalamic CRH (41 aa peptide) → anterior pituitary corticotrophs release ACTH (39 aa, derived from POMC processing) → adrenal cortex produces cortisol. Cortisol feeds back at both hypothalamic and pituitary levels (negative feedback). The HPA axis follows a circadian rhythm (cortisol peaks in early morning) and is activated by physical and psychological stress. Corticotropin (therapeutic ACTH) directly stimulates adrenal cortisol production. Cosyntropin (ACTH 1-24, the biologically active N-terminal fragment) is used in the ACTH stimulation test — 250μg IV/IM with cortisol measured at 30 and 60 minutes; cortisol >18-20 μg/dL indicates normal adrenal function. Pasireotide suppresses ACTH from pituitary corticotroph adenomas in Cushing's disease.