Secondary Adrenal Insufficiency and Steroid-Induced Suppression

Secondary adrenal insufficiency occurs when the pituitary does not release enough adrenocorticotropic hormone (ACTH). Without ACTH stimulation, the adrenal cortex produces too little cortisol. Tertiary adrenal insufficiency is closely related but begins higher in the axis: reduced hypothalamic corticotropin-releasing hormone (CRH) leads to low ACTH and low cortisol. Exogenous glucocorticoids are the most common cause of adrenal insufficiency. Prednisone, dexamethasone, methylprednisolone, hydrocortisone, and other corticosteroids suppress CRH and ACTH through negative feedback. The hypothalamic-pituitary-adrenal (HPA) axis responds as though the body already has abundant cortisol. Over time, the adrenal cortex receives too little ACTH stimulation and may atrophy. Suppression is not limited to oral therapy. High-dose or prolonged inhaled, intranasal, topical, ophthalmic, intra-articular, or epidural corticosteroids can contribute, especially when several routes are used together. Risk rises with higher potency, higher dose, longer exposure, divided or evening dosing, and interacting medications that increase steroid levels. The clinical distinction from primary adrenal insufficiency follows the anatomy. Aldosterone secretion is mainly controlled by the renin-angiotensin-aldosterone system, not ACTH. Therefore, aldosterone is usually preserved in secondary and tertiary disease. This produces a characteristic...