Secondary or central adrenal insufficiency (CAI) is defined as the impairment of pituitary hormone synthesis and release of ACTH, as well as an impaired release or action of CRH from the hypothalamus when caused by disease or injury to the hypothalamic-pituitary area, or when prolonged exogenous glucocorticoid administration exceeding physiological replacement doses. Cortisol production and release are therefore reduced in the absence of ACTH or CRH in secondary adrenal insufficiency. The gene discussed is CRH; the disease is Adrenal insufficiency.