Addison’s disease, clinically known as primary adrenal insufficiency, is a rare, chronic endocrine disorder. It occurs when the adrenal glands small, triangular organs located on top of each kidney are damaged and fail to produce sufficient hormones.

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Specifically, the adrenal cortex (the outer layer of the gland) becomes unable to produce two critical classes of hormones:

• Cortisol (Glucocorticoids): Often called the "stress hormone," cortisol helps regulate metabolism, blood pressure, immune response, and the body's reaction to stress.

• Aldosterone (Mineralocorticoids): This hormone regulates the balance of sodium and potassium in the blood, which is essential for maintaining blood pressure and fluid volume.

Without these hormones, the body cannot maintain essential functions, leading to severe, progressive illness.

 

Who is Affected?

Addison’s disease is rare, affecting approximately 4 to 11 people per 100,000 in the general population. While it can develop at any age, it most frequently presents in adults between 30 and 50 years old.​

• Gender: In cases caused by autoimmune factors, women are more frequently affected than men.

• Genetics: Individuals with a family history of other autoimmune conditions (such as Type 1 Diabetes, Hashimoto’s thyroiditis, or Vitiligo) are at a higher risk.

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Causes of Addison’s Disease

The causes of Addison’s disease are categorized by the type of damage inflicted on the adrenal glands.

1. Autoimmune Adrenalitis (Most Common)

In developed countries, 70% to 90% of cases are autoimmune. The body’s immune system mistakenly identifies the adrenal cortex as foreign and attacks it. This process is often gradual, destroying the gland over months or years.

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2. Infections

• Tuberculosis (TB): Historically the leading cause and still a primary cause in developing nations. TB bacteria can infiltrate and destroy the adrenal glands.

• Fungal Infections: Disseminated infections like histoplasmosis or blastomycosis.

• Viral Infections: HIV/AIDS and cytomegalovirus (CMV) can lead to adrenal destruction, particularly in immunocompromised patients.

 

3. Other Causes

• Adrenal Hemorrhage: Bleeding into the adrenal glands, often caused by severe sepsis (Waterhouse-Friderichsen syndrome) or anticoagulant medication.

• Cancer: Metastatic cancer spreading from the lungs, breasts, or colon to the adrenal glands.

• Genetic Disorders: Conditions such as Adrenoleukodystrophy (ALD) affect the adrenal glands' ability to function.

• Medications: Certain drugs, such as etomidate (anesthesia) or ketoconazole (antifungal), can inhibit cortisol production.

 

​Symptoms and Clinical Presentation

Symptoms usually develop slowly, often over several months. Because they are non-specific (vague), they are frequently ignored or misdiagnosed until a stressful event triggers a crisis.

Common Physical Symptoms:

• Chronic Fatigue: Profound, worsening tiredness and muscle weakness.

• Hyperpigmentation: Darkening of the skin, particularly on "pressure points" (knuckles, elbows, knees), scars, and the inside of the cheeks or lips. This "bronze" skin is a hallmark sign caused by elevated ACTH levels stimulating melanin.

• Weight Loss: Unintentional weight loss and loss of appetite (anorexia).

• Gastrointestinal Issues: Nausea, vomiting, diarrhea, and abdominal pain.

• Salt Cravings: An intense desire for salty foods due to sodium loss (from low aldosterone).

• Hypotension: Low blood pressure, often causing dizziness or fainting upon standing (orthostatic hypotension).

 

Psychological and Gender-Specific Symptoms

• Mood Changes: Irritability, depression, and difficulty concentrating.

• In Women: Loss of body hair (axillary and pubic) and decreased libido due to the loss of adrenal androgens (DHEA).

 

Diagnosing Addison’s Disease

Diagnosis requires biochemical testing to confirm low hormone levels.

1. Blood Tests:

   • Electrolytes: typically show low sodium (hyponatremia) and high potassium (hyperkalemia).

   • Morning Cortisol: Levels will be abnormally low.

   • ACTH (Adrenocorticotropic Hormone): Levels will be high. The pituitary gland screams ACTH to try to wake up the adrenals, but the adrenals cannot respond.

   • Antibody Testing: Checking for 21-hydroxylase antibodies confirms an autoimmune cause.

2. ACTH Stimulation Test (Gold Standard):

   • The patient’s baseline cortisol is measured.

   • Synthetic ACTH (cosyntropin) is injected.

   • Cortisol is measured again after 30–60 minutes.

   • Result: In a healthy person, cortisol levels spike. In a person with Addison’s, the damaged adrenals cannot produce cortisol, so levels remain flat/low.

3. Imaging:

   • CT Scan or MRI: Used to visualize the adrenal glands. Autoimmune disease typically causes small, shrunken glands, while infections or tumors may cause enlarged glands or calcium deposits.

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Treatment and Management

Addison’s disease is currently not curable, but it is manageable with lifelong hormone replacement therapy. The goal is to mimic the natural rhythm of the body's hormones.

• Glucocorticoid Replacement: Medications like hydrocortisone, prednisone, or dexamethasone replace cortisol. These are usually taken in divided doses (higher in the morning) to mimic the natural circadian rhythm.​

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• Mineralocorticoid Replacement: Fludrocortisone is prescribed to replace aldosterone. This helps retain sodium and maintain blood pressure.

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• Androgen Replacement (Optional): DHEA supplements may be prescribed for women to improve libido and overall well-being.

• Dietary Adjustments: Patients may be advised to maintain a liberal salt intake, especially during hot weather or exercise.

 

Complications: The Addisonian Crisis

The most severe complication is the Addisonian Crisis (or Adrenal Crisis). This is a life-threatening medical emergency caused by a severe lack of cortisol.

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• Triggers: Physical stress (infection, fever, surgery, car accident) or suddenly stopping medication.

• Symptoms of Crisis:

  • Severe, penetrating pain in the lower back, abdomen, or legs.

  • Severe vomiting and diarrhea leading to dehydration.

  • Low blood pressure, loss of consciousness, and shock.

  • Confusion or psychosis.

• Treatment: Requires immediate intravenous (IV) injections of hydrocortisone and saline (saltwater) fluids. Without immediate treatment, it can be fatal.

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Prevention and Outlook

Can Addison's Disease be prevented? Currently, there is no way to prevent the autoimmune destruction of the adrenal glands. However, for those already diagnosed, preventing an adrenal crisis is the primary goal.

Prevention Strategies for Patients:

1. "Sick Day Rules": Patients must be taught to temporarily increase their medication dosage ("stress dosing") during illness, fever, or before surgical procedures.

2. Medical Alert Identification: Patients should always wear a bracelet or carry a card stating, "Adrenal Insufficiency: Needs Steroids in Emergency."

3. Emergency Kit: Patients should carry an injectable form of corticosteroids (like a solucortef injection) for emergencies where they cannot swallow pills (e.g., vomiting).

Prognosis: With proper compliance to medication and monitoring, people with Addison’s disease can expect a normal life expectancy and can lead active, healthy lives.