- Addison’s disease, also known as primary adrenal insufficiency, is a rare but serious endocrine disorder characterized by the inadequate production of cortisol and often aldosterone by the adrenal cortex.
- Cortisol is a glucocorticoid that regulates metabolism, immune function, and the body’s stress response, while aldosterone is a mineralocorticoid that controls sodium and potassium balance, as well as blood pressure. A deficiency in these hormones disrupts multiple physiological systems, leading to symptoms that can range from subtle and nonspecific to life-threatening.
- The most common cause of Addison’s disease in industrialized countries is autoimmune adrenalitis, in which the immune system mistakenly attacks and destroys the adrenal cortex. This autoimmune process is frequently associated with other autoimmune conditions, such as type 1 diabetes and autoimmune thyroid disease, as part of autoimmune polyendocrine syndromes. In developing regions, tuberculosis remains a leading cause of adrenal destruction. Other less common causes include metastatic cancer to the adrenal glands, fungal infections, adrenal hemorrhage, and rare genetic or congenital conditions affecting adrenal development or function.
- The clinical presentation of Addison’s disease is often insidious and nonspecific, which can delay diagnosis. Common symptoms include chronic fatigue, weight loss, muscle weakness, abdominal pain, nausea, vomiting, diarrhea, and irritability or depression. A hallmark sign is hyperpigmentation of the skin and mucous membranes, which occurs due to increased secretion of adrenocorticotropic hormone (ACTH). In primary adrenal insufficiency, low cortisol levels fail to provide feedback inhibition on the pituitary, leading to excess ACTH, which shares a precursor molecule with melanocyte-stimulating hormone (MSH). Patients may also experience low blood pressure, salt cravings, and dehydration due to aldosterone deficiency, which causes sodium loss and potassium retention.
- A potentially fatal complication of Addison’s disease is the Addisonian crisis (acute adrenal crisis). This medical emergency can be triggered by stress, infection, trauma, or abrupt withdrawal of corticosteroid therapy. Symptoms include severe hypotension, shock, hypoglycemia, confusion, and electrolyte imbalances (particularly hyponatremia and hyperkalemia). Without prompt treatment with intravenous hydrocortisone and fluid replacement, adrenal crisis can be rapidly fatal.
- Diagnosis of Addison’s disease relies on both clinical suspicion and laboratory testing. Key findings include low serum cortisol, elevated ACTH, and electrolyte abnormalities such as hyponatremia and hyperkalemia. The ACTH stimulation test (cosyntropin test) is the gold standard for diagnosis: failure of cortisol levels to rise after ACTH administration confirms adrenal insufficiency. Imaging studies like CT or MRI may be used to evaluate adrenal size and morphology, helping to distinguish autoimmune destruction from infectious, hemorrhagic, or neoplastic causes.
- Treatment involves lifelong hormone replacement therapy. Cortisol deficiency is managed with oral glucocorticoids such as hydrocortisone, prednisone, or dexamethasone, while aldosterone deficiency is treated with fludrocortisone, a synthetic mineralocorticoid. Patients are advised to increase doses during periods of physical stress or illness to mimic the natural rise in cortisol. Medical identification bracelets and emergency hydrocortisone injections are often recommended to prevent Addisonian crises. With proper management, most individuals with Addison’s disease can lead relatively normal lives, although ongoing monitoring and dose adjustments are necessary.
