Addison's disease is a rare, chronic endocrine disorder characterized by the inadequate production of steroid hormones—primarily cortisol and aldosterone—by the adrenal cortex. It results from the progressive bilateral destruction of the adrenal glands. Left untreated, it is universally fatal; however, with lifelong hormone replacement therapy, patients typically achieve a normal lifespan.

• Autoimmune Adrenalitis: Responsible for approximately 80% of cases in developed nations. It involves autoimmune destruction of the adrenal cortex, frequently associated with anti-21-hydroxylase antibodies. It can occur isolated or as part of Autoimmune Polyglandular Syndrome Type 1 or 2 (APS-1, APS-2).
• Infections: Tuberculosis remains a leading cause globally. Fungal infections (histoplasmosis, coccidioidomycosis) and viral infections (HIV/AIDS-associated cytomegalovirus) also cause adrenal destruction.
• Hemorrhage or Infarction: Bilateral adrenal hemorrhage secondary to sepsis (Waterhouse-Friderichsen syndrome) or anticoagulant therapy.
• Metastatic Disease: Infiltration of the adrenal glands by lung, breast, or gastric cancers.
• Genetic Factors: Association with HLA-DR3-DQ2 and HLA-DR4-DQ8 genotypes.

The destruction of over 90% of the adrenal cortex leads to a profound deficiency of glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens.

• Cortisol Deficiency: Impairs gluconeogenesis, causing hypoglycemia and profound sensitivity to insulin. It also leads to systemic vasodilation, resulting in hypotension.


• Aldosterone Deficiency: Impairs sodium reabsorption and potassium/hydrogen excretion in the renal distal tubules, causing hyponatremia, hyperkalemia, metabolic acidosis, and hypovolemia.


• Compensatory Mechanics: The lack of cortisol negative feedback prompts the pituitary gland to overproduce adrenocorticotropic hormone (ACTH) and pro-opiomelanocortin (POMC). Cleavage of POMC yields melanocyte-stimulating hormone (MSH), which drives melanin production.

• Prevalence: 100 to 140 cases per million individuals in Western populations.
• Incidence: 4 to 6 new cases per million annually.
• Demographics: Most commonly diagnosed between 30 and 50 years of age. Autoimmune forms show a female-to-male ratio of approximately 2:1.

• Personal or family history of autoimmune disorders (Type 1 diabetes, Hashimoto's thyroiditis, vitiligo, pernicious anemia).
• Active tuberculosis or chronic systemic fungal infections.
• History of bilateral adrenalectomy.
• Anticoagulant therapy combined with systemic physiological stress.

• Vitals: Orthostatic hypotension (systolic drop >20 mmHg), tachycardia, low-grade fever (unless in adrenal crisis, where high fever may present).
• Inspection: Generalized bronze-like hyperpigmentation, vitiligo (in autoimmune cases), thin or cachectic appearance, loss of secondary hair in females.
• Palpation: Diffuse abdominal tenderness without rebound.

Morning Serum Cortisol Type: Blood Test (8:00 AM) * Purpose: Initial screening of adrenal function.

• Expected Findings: Low (< 3 mcg/dL strongly diagnostic; > 15 mcg/dL rules out).


• Interpretation: Low values indicate adrenal insufficiency.

• Purpose: Differentiating primary from secondary adrenal insufficiency.


• Expected Findings: Elevated (> 100 pg/mL).


• Interpretation: High ACTH confirms a primary adrenal defect (Addison's).

• Purpose: Assessment of mineralocorticoid deficiency.


• Expected Findings: Hyponatremia, hyperkalemia.


• Interpretation: Reflects low aldosterone-mediated renal sodium retention.

• Purpose: Confirming adrenal insufficiency.


• Expected Findings: Cortisol fails to rise above 18 mcg/dL 30-60 minutes post-injection.


• Interpretation: Blunted response confirms adrenal insufficiency.