Addison's Disease (Primary Adrenal Insufficiency): Symptoms, Causes, and Treatment

Addison's disease is primary adrenal insufficiency—failure of the adrenal cortex to produce adequate cortisol and, usually, aldosterone. Incidence: 4–6 per 100,000; peak onset 30–50 years.

Pathophysiology

Autoimmune adrenalitis (80% in developed nations): 21-hydroxylase antibodies destroy cortical cells. Often part of autoimmune polyendocrine syndromes (APS-1, APS-2).
Other causes: TB (leading cause globally), fungal infections, metastatic cancer, hemorrhage (Waterhouse-Friderichsen), adrenoleukodystrophy, medications (ketoconazole, etomidate, checkpoint inhibitors).

Clinical Features

Glucocorticoid deficiency: Fatigue, weakness, weight loss, anorexia, nausea/vomiting, abdominal pain, hypoglycemia, hypotension, hyperpigmentation (↑ACTH/MSH).
Mineralocorticoid deficiency: Salt craving, volume depletion, orthostatic hypotension, hyperkalemia, metabolic acidosis.
Androgen deficiency (women): Loss of axillary/pubic hair, reduced libido.

Adrenal Crisis (Medical Emergency)

Precipitated by stress (infection, trauma, surgery) in untreated/undertreated patients. Profound hypotension, shock, altered mental status, fever, abdominal pain. Immediate IV hydrocortisone 100 mg + fluid resuscitation.

Diagnosis

• Low morning cortisol (<3 μg/dL) + elevated ACTH (>100 pg/mL) = primary AI.
• Confirm with ACTH stimulation test (250 μg cosyntropin): cortisol <18–20 μg/dL at 30/60 min.
• 21-hydroxylase antibodies; adrenal CT for structural causes.

Treatment

Lifelong replacement: Hydrocortisone 15–25 mg/day (divided: 2/3 AM, 1/3 PM) or prednisolone 3–5 mg/day. Fludrocortisone 0.05–0.2 mg/day for mineralocorticoid replacement. Stress dosing: double/triple glucocorticoid for illness/surgery. Patient education: medical alert ID, emergency injection kit, sick-day rules.