Addison's Disease – Top USMLE Diseases

Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. These medications are also used for conditions requiring physiologic glucocorticoid replacement. Despite their extensive use, glucocorticoids can produce many and varied adverse effects and should be used judiciously. Because of their immunosuppressive effect, these medications may predispose individuals to infection and should be avoided in those with uncontrolled infections. In addition, long-term therapy can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, so discontinuation of therapy should be done carefully to avoid adrenal insufficiency.

Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. The work of hormones allows the body to maintain homeostasis and regulate growth and development. Hormones are typically either made from amino acids or derived from cholesterol (the latter group being known as steroid hormones). Hormones exert their effects by binding to receptors either on the cell surface (most amino acid–based hormones) or within the cytosol (steroid hormones). Ultimately, binding to receptors triggers changes in gene expression or enzymatic activity within the cell.

The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. The outer zona glomerulosa secretes mineralocorticoids (primarily aldosterone); the middle zona fasciculata secretes glucocorticoids (primarily cortisol); and the innermost zona reticularis secretes androgens. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. The medullary cells function more like neurosecretory postsynaptic neurons rather than traditional endocrine cells. The adrenal glands have a rich vascular supply and complex relationships with their surrounding organs.

Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by adrenal gland disorder (autoimmune disease, infections, and malignancy, among others). Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Diagnosis is by demonstrating hypocortisolism (via cortisol and ACTH levels and ACTH-stimulation test) and determining the etiology (adrenal autoantibodies, imaging). Glucocorticoid replacement is needed in all forms of AI. Additionally, in primary AI, mineralocorticoid is given to prevent volume depletion, salt loss, and hyperkalemia. Adrenal crisis is a medical emergency; management requires prompt IV hydration and administration of IV glucocorticoids without waiting for initial hormone results.