Abstract:

Addison’s disease, also referred to as primary adrenal insufficiency, is a rare but potentially life-threatening endocrine disorder characterized by insufficient production of glucocorticoids, mineralocorticoids, and adrenal androgens due to autoimmune destruction, infections, or genetic defects affecting the adrenal cortex. Early diagnosis is critical to prevent adrenal crises, which can lead to severe hypotension, electrolyte imbalances, and multi-organ dysfunction. Clinical manifestations often begin subtly, including fatigue, weight loss, anorexia, hyperpigmentation, orthostatic hypotension, and gastrointestinal disturbances, which can be misattributed to more common conditions. Biochemical evaluation typically demonstrates hyponatremia, hyperkalemia, elevated adrenocorticotropic hormone (ACTH) levels, and reduced cortisol production, while confirmatory testing may include the ACTH stimulation test. Advances in imaging, autoantibody detection, and genetic analysis have improved early detection and differentiation from secondary adrenal insufficiency. Management involves lifelong glucocorticoid and mineralocorticoid replacement therapy, patient education on stress-dose adjustments, and regular monitoring of electrolytes and cardiovascular status. This review provides a detailed overview of the clinical presentation, diagnostic challenges, early detection strategies, and modern therapeutic approaches for Addison’s disease, emphasizing the importance of timely intervention to prevent morbidity and improve patient quality of life. Addison’s disease, or primary adrenal insufficiency, is a severe endocrine disorder resulting from inadequate production of cortisol, aldosterone, and adrenal androgens due to autoimmune destruction, infections, or genetic abnormalities. Early identification of the disease is crucial to prevent life-threatening adrenal crises, which manifest as profound hypotension, electrolyte imbalances, hypoglycemia, and multiorgan failure. Clinical presentation is often insidious, including fatigue, weight loss, hyperpigmentation, dizziness, gastrointestinal disturbances, and salt craving, frequently leading to diagnostic delays. Biochemical findings include low serum cortisol, elevated adrenocorticotropic hormone (ACTH), hyponatremia, hyperkalemia, and metabolic acidosis, while the ACTH stimulation test confirms adrenal insufficiency. Imaging and autoantibody testing aid in etiology differentiation and early detection. Management involves lifelong glucocorticoid and mineralocorticoid replacement therapy, patient education on stress-dose adjustments, and careful monitoring of electrolytes, blood pressure, and metabolic status. Recent advances in early detection, including 21-hydroxylase antibody screening and genetic evaluation, improve prognostic assessment and allow timely intervention. This review summarizes the clinical, immunological, and biochemical aspects of Addison’s disease, emphasizing early diagnosis, preventive strategies, and modern treatment protocols to optimize patient outcomes and minimize complications.