Secondary Adrenal Insufficiency and Steroid-Induced Suppression

Cortisol production depends on a functioning hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary to release adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal cortex to produce cortisol. Secondary adrenal insufficiency occurs when the pituitary does not release enough ACTH. Tertiary adrenal insufficiency occurs when hypothalamic CRH and pituitary ACTH are suppressed. Exogenous glucocorticoid therapy is the most common cause of this tertiary form. Synthetic steroids provide negative feedback to the HPA axis; with sustained exposure, endogenous ACTH falls and the adrenal cortex gradually loses its capacity to make adequate cortisol. The clinical picture differs from primary adrenal insufficiency because aldosterone is regulated mainly by the renin-angiotensin-aldosterone system, not ACTH. Mineralocorticoid production is therefore usually preserved in secondary and tertiary disease. This distinction explains several high-yield findings: - Hyperkalemia and severe salt-wasting volume depletion are typical of primary adrenal insufficiency, not central disease. - Hyperpigmentation does not occur in central disease because ACTH and its POMC precursor are low rather than elevated. - Hyponatremia can still occur. Cortisol deficiency impairs free-water excretion, so the patient...