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Addison's Disease

Discover the hidden truths about Addison's Disease, a rare and often misunderstood condition affecting the adrenal glands, that will leave you questioning everything you thought you knew.

USMLE Guide: Addison's Disease


Addison's disease, also known as primary adrenal insufficiency, is a rare and chronic condition characterized by the inadequate production of hormones by the adrenal glands. This guide aims to provide an overview of Addison's disease, including its etiology, clinical presentation, diagnostic approach, and management strategies.


  • Addison's disease has an estimated prevalence of 1 in 10,000 individuals.
  • It affects both males and females equally.
  • The peak age of onset is between 30 and 50 years, but it can occur at any age.

Etiology and Pathophysiology

  • The most common cause of Addison's disease is autoimmune destruction of the adrenal cortex (80-90% of cases).
  • Other causes include infectious (e.g., tuberculosis, fungal infections), infiltrative (e.g., metastatic cancer, amyloidosis), and genetic (e.g., congenital adrenal hyperplasia) etiologies.
  • Adrenal gland destruction leads to decreased production of cortisol, aldosterone, and adrenal androgens, resulting in a range of clinical manifestations.

Clinical Presentation

Non-specific Symptoms

  • Fatigue, weakness, and lethargy.
  • Weight loss and decreased appetite.
  • Hyperpigmentation of the skin (especially in sun-exposed areas).
  • Salt craving and low blood pressure.

Acute Adrenal Crisis

  • Life-threatening condition precipitated by stress, infection, surgery, or trauma.
  • Symptoms include severe hypotension, shock, altered mental status, and electrolyte disturbances (e.g., hyponatremia, hyperkalemia).

Laboratory Findings

  • Hyponatremia, hyperkalemia, and metabolic acidosis.
  • Hypoglycemia may be present in severe cases.
  • Low levels of cortisol and aldosterone.
  • Elevated levels of adrenocorticotropic hormone (ACTH).

Diagnostic Approach

Initial Evaluation

  • Detailed history and physical examination.
  • Measurement of morning cortisol levels.
  • ACTH stimulation test to assess adrenal gland function.
  • Serum electrolyte and glucose levels.

Confirmatory Testing

  • Measurement of renin, aldosterone, and ACTH levels.
  • Imaging studies (e.g., CT or MRI) to identify adrenal gland abnormalities.


Hormone Replacement Therapy

  • Oral glucocorticoids (e.g., hydrocortisone, prednisone) to replace cortisol.
  • Mineralocorticoid replacement with fludrocortisone to replace aldosterone.

Stress Dosing

  • Increased glucocorticoid dose during periods of stress (e.g., surgery, illness) to prevent adrenal crisis.

Patient Education

  • Teach patients about the importance of daily medication adherence.
  • Instruct patients to carry an emergency card or wear a medical ID bracelet indicating their condition.
  • Educate patients on recognizing signs and symptoms of adrenal crisis and the appropriate steps to take.


  • With appropriate hormone replacement therapy, the prognosis for individuals with Addison's disease is generally good.
  • Lifelong treatment and regular follow-up with an endocrinologist are necessary to optimize patient outcomes and prevent complications.


Addison's disease is a chronic condition that requires early recognition and appropriate management to prevent life-threatening complications. This USMLE guide has provided an overview of the epidemiology, etiology, clinical presentation, diagnostic approach, and management strategies for Addison's disease. By understanding the key concepts outlined here, healthcare professionals can confidently diagnose and treat patients with this condition.

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