Addison's Disease: Symptoms, Causes & Lifelong Treatment

What Is Addison's Disease?

Addison's disease (primary adrenal insufficiency) is a rare condition where the adrenal glands are damaged and cannot produce enough of the hormones cortisol and aldosterone. It affects approximately 100-140 people per million and requires lifelong hormone replacement therapy. The most common cause in developed countries is autoimmune destruction of the adrenal cortex.

The adrenal glands are two small, triangular-shaped glands that sit on top of each kidney. Despite their small size, they produce hormones that are absolutely essential for life. The outer layer of the adrenal glands, called the adrenal cortex, produces two critically important hormones: cortisol and aldosterone.

Cortisol, often called the "stress hormone," plays a vital role in numerous body functions. It helps regulate metabolism, controls how the body uses carbohydrates, fats, and proteins for energy, reduces inflammation, and helps the body respond to stress. When you face a serious infection, injury, or stressful situation, your body normally increases cortisol production to help you cope. Without adequate cortisol, even minor illnesses can become life-threatening.

Aldosterone regulates the balance of sodium and potassium in your blood, which in turn controls blood pressure and maintains proper fluid balance. When aldosterone levels are too low, the body loses too much sodium and retains too much potassium, leading to low blood pressure, dehydration, and potentially dangerous electrolyte imbalances.

When you have Addison's disease, the adrenal cortex is damaged and can no longer produce adequate amounts of these essential hormones. This condition is also called primary adrenal insufficiency or primary hypoadrenalism, distinguishing it from secondary adrenal insufficiency, which is caused by problems with the pituitary gland rather than the adrenal glands themselves.

How Common Is Addison's Disease?

Addison's disease is relatively rare, affecting approximately 100-140 people per million population. The annual incidence is about 4-6 new cases per million people. While it can occur at any age, it most commonly begins between ages 20 and 40. The condition affects men and women equally, although autoimmune Addison's disease is slightly more common in women.

What Causes Addison's Disease?

In developed countries, the most common cause of Addison's disease is autoimmune adrenalitis, accounting for 70-90% of cases. In this condition, the body's immune system mistakenly attacks and gradually destroys the adrenal cortex. This process often takes months or years, which explains why symptoms typically develop gradually.

People with autoimmune Addison's disease often have or are at increased risk for other autoimmune conditions. These may include:

• Autoimmune thyroid disease (Hashimoto's thyroiditis or Graves' disease)
• Type 1 diabetes
• Vitiligo (patches of skin losing pigmentation)
• Pernicious anemia
• Celiac disease

Other causes of Addison's disease include:

• Tuberculosis - the leading cause worldwide and historically the most common cause before effective TB treatment
• Fungal infections - particularly in immunocompromised individuals
• HIV/AIDS-related infections
• Cancer metastases - especially from lung, breast, or melanoma
• Adrenal hemorrhage - bleeding into the adrenal glands
• Genetic conditions - such as adrenoleukodystrophy or congenital adrenal hyperplasia

What Are the Symptoms of Addison's Disease?

The main symptoms of Addison's disease include chronic fatigue and weakness, unexplained weight loss, darkening of the skin (hyperpigmentation), low blood pressure causing dizziness, salt cravings, nausea and abdominal pain, and muscle or joint pain. Symptoms typically develop gradually over months and can be easily mistaken for other conditions.

The symptoms of Addison's disease often develop slowly over several months, which can make diagnosis challenging. Because cortisol and aldosterone affect so many body systems, symptoms can be vague and varied. Many people are initially misdiagnosed with depression, chronic fatigue syndrome, or gastrointestinal problems before the true cause is identified.

The gradual onset occurs because the adrenal glands have significant reserve capacity. Symptoms typically don't appear until about 90% of the adrenal cortex has been destroyed. This means the disease may be progressing silently for a long time before becoming apparent.

Common Symptoms of Untreated Addison's Disease

The following symptoms are characteristic of Addison's disease and tend to worsen over time without treatment:

• Chronic fatigue and weakness: This is often the earliest and most prominent symptom. The fatigue is profound, doesn't improve with rest, and worsens as the day progresses.
• Unexplained weight loss and decreased appetite: Loss of appetite, nausea, and metabolic changes lead to gradual weight loss, often 5-15 pounds.
• Hyperpigmentation (skin darkening): One of the most distinctive signs of Addison's disease. The skin becomes darker, especially in sun-exposed areas, skin folds, creases (palms, knuckles, elbows, knees), scars, lips, and inside the mouth. This occurs because low cortisol triggers increased production of a hormone (ACTH) that also stimulates pigment-producing cells.
• Low blood pressure (hypotension): Blood pressure is often low even when lying down and drops further upon standing (orthostatic hypotension), causing dizziness, lightheadedness, or fainting.
• Salt craving: The loss of aldosterone causes the body to excrete excessive sodium, leading to intense cravings for salty foods.
• Gastrointestinal symptoms: Nausea, vomiting, abdominal pain, and diarrhea are common and can be mistaken for other conditions.
• Muscle and joint pain: Generalized aches and pains in muscles and joints.
• Irritability and depression: Mood changes, difficulty concentrating, and depression are common.
• In women: Reduced libido and loss of body hair (particularly underarm and pubic hair) due to loss of adrenal androgens.

What Is an Adrenal Crisis (Addisonian Crisis)?

An adrenal crisis is a life-threatening medical emergency that occurs when cortisol levels drop critically low. Symptoms include severe weakness, confusion, severe abdominal pain, vomiting, very low blood pressure, and potential loss of consciousness. Without immediate treatment with injectable hydrocortisone and IV fluids, it can be fatal. Triggers include infections, surgery, vomiting/diarrhea, or missed medication doses.

An adrenal crisis (also called an Addisonian crisis) is the most serious and potentially fatal complication of Addison's disease. It occurs when the body's cortisol levels fall so low that vital functions begin to fail. This is a medical emergency that requires immediate treatment.

The crisis can occur in two scenarios: when someone has undiagnosed Addison's disease and faces a significant stress (like an infection), or when someone with known Addison's disease encounters a situation requiring more cortisol than their usual medication provides.

Symptoms of Adrenal Crisis

The symptoms of adrenal crisis can develop rapidly over hours and include:

• Severe weakness - unable to stand or walk
• Severe abdominal, leg, or back pain
• Nausea and severe vomiting
• Diarrhea
• Confusion or altered consciousness
• Very low blood pressure
• High fever or abnormally low temperature
• Loss of consciousness

What Triggers an Adrenal Crisis?

An adrenal crisis is usually triggered by a physical stress that increases the body's need for cortisol. Common triggers include:

• Infections - especially those causing fever
• Gastrointestinal illness with vomiting or diarrhea (which prevents medication absorption)
• Surgery or dental procedures
• Severe injury or trauma
• Missing medication doses
• Severe emotional stress
• Extreme heat or physical exertion

When Should You Seek Medical Care?

Seek emergency care immediately for signs of adrenal crisis: severe weakness, confusion, severe abdominal pain, vomiting, or very low blood pressure. Contact your healthcare provider if you have unexplained fatigue, weight loss, skin darkening, or salt cravings that could indicate Addison's disease. If you have Addison's disease and experience illness with fever or cannot keep medication down, seek urgent medical advice.

If you suspect you might have Addison's disease based on symptoms like persistent fatigue, unexplained weight loss, skin darkening, low blood pressure, and salt cravings, you should contact your healthcare provider for evaluation. While these symptoms can have many causes, it's important to rule out Addison's disease because untreated cases can progress to life-threatening adrenal crisis.

Seek Immediate Emergency Care If:

• You have signs of adrenal crisis (severe weakness, confusion, severe pain, vomiting, very low blood pressure)
• You have Addison's disease and cannot keep medication down due to vomiting
• You have Addison's disease and have a serious injury or illness

Contact Your Healthcare Provider If:

• You have Addison's disease and develop an illness with fever
• You're unsure whether to increase your medication dose
• Your medication is running out and you need a new prescription
• You're planning surgery or a dental procedure

How Is Addison's Disease Diagnosed?

Addison's disease is diagnosed through blood tests measuring cortisol levels (especially morning cortisol), electrolytes (low sodium, high potassium), and ACTH levels. The ACTH stimulation test (Synacthen test) is the gold standard, measuring cortisol response to synthetic ACTH. Additional tests may include adrenal antibodies to confirm autoimmune cause and imaging to assess adrenal gland structure.

Diagnosing Addison's disease can be challenging because symptoms develop gradually and overlap with many other conditions. A high index of suspicion is needed, particularly in patients with unexplained fatigue, weight loss, hyperpigmentation, and low blood pressure. The diagnosis is confirmed through a combination of blood tests and specialized hormone testing.

Initial Blood Tests

When Addison's disease is suspected, initial blood tests typically reveal characteristic abnormalities:

• Low morning cortisol: Blood cortisol levels vary throughout the day, peaking in the early morning. A morning cortisol level below 3 mcg/dL (80 nmol/L) strongly suggests adrenal insufficiency.
• Low sodium (hyponatremia): Due to aldosterone deficiency
• High potassium (hyperkalemia): Also due to aldosterone deficiency
• High ACTH: In primary adrenal insufficiency, ACTH levels are elevated because the pituitary is trying to stimulate the failing adrenal glands
• Low blood glucose: Cortisol helps maintain blood sugar levels

ACTH Stimulation Test (Synacthen Test)

The ACTH stimulation test is the gold standard for diagnosing Addison's disease. It works by testing whether the adrenal glands can respond normally to stimulation.

During the test:

1. A baseline blood sample is taken to measure cortisol
2. A synthetic form of ACTH (called Synacthen or cosyntropin) is injected
3. Blood samples are taken 30 and 60 minutes later
4. In healthy people, cortisol rises significantly; in Addison's disease, there is little or no response

This test is typically performed in a hospital or specialist clinic because, rarely, it can cause an allergic reaction.

Additional Diagnostic Tests

Once Addison's disease is confirmed, additional tests help identify the cause:

• Adrenal antibodies: Testing for 21-hydroxylase antibodies can confirm an autoimmune cause
• CT or MRI scan: Imaging of the adrenal glands can reveal enlargement (suggesting infection or cancer) or shrinkage (typical of autoimmune destruction)
• Chest X-ray: To check for tuberculosis if suspected

How Is Addison's Disease Treated?

Addison's disease is treated with lifelong hormone replacement therapy. This includes hydrocortisone tablets (taken 2-3 times daily to replace cortisol) and fludrocortisone (taken once daily to replace aldosterone). Doses must be increased during illness, stress, or surgery. All patients should carry emergency injectable hydrocortisone and a steroid emergency card. With proper treatment, most people can live normal lives.

The treatment for Addison's disease is relatively straightforward: replacing the hormones that the adrenal glands can no longer produce. With proper treatment, most people with Addison's disease can live normal, active, and long lives. However, treatment must be continued for life, and patients must learn to adjust their medication during times of physical stress.

Cortisol Replacement: Hydrocortisone

Hydrocortisone is the primary medication used to replace cortisol. It's taken as tablets, typically in divided doses to mimic the body's natural cortisol rhythm. A common regimen is:

• Largest dose in the morning upon waking (when natural cortisol would peak)
• Smaller dose at midday
• Sometimes a small evening dose (though this may interfere with sleep)

The total daily dose typically ranges from 15-25 mg, though this varies between individuals. Your doctor will work with you to find the optimal dose that controls symptoms without causing side effects from excess cortisol.

Aldosterone Replacement: Fludrocortisone

Fludrocortisone replaces aldosterone and is taken once daily, usually in the morning. The typical dose is 0.05-0.2 mg. This medication helps maintain proper sodium and potassium balance and supports healthy blood pressure.

Adjusting Medication During Illness or Stress

One of the most critical aspects of Addison's disease management is knowing when and how to increase your hydrocortisone dose. The body normally increases cortisol production during physical stress; since your adrenal glands cannot do this, you must do it with medication.

Emergency Injectable Hydrocortisone

All people with Addison's disease should have an emergency injection kit containing hydrocortisone that can be given intramuscularly. This is crucial for situations when:

• Vomiting prevents keeping oral medication down
• An adrenal crisis is developing
• You're far from medical care and become seriously ill

You, and ideally family members or close friends, should learn how to administer the injection. After using emergency hydrocortisone, always seek medical care.

What If You Miss a Dose?

If you forget to take a dose or are unsure whether you've taken it, take an extra dose. It's safer to take slightly too much than to miss a dose entirely. Never suddenly stop taking your medication without medical supervision.

What Is It Like Living with Addison's Disease?

Most people with Addison's disease can live normal, active lives with proper management. Key aspects include taking medication consistently every day, learning to adjust doses during illness or stress, always carrying emergency medication and medical ID, having regular medical follow-ups, and educating family and friends about the condition. Many patients work, exercise, travel, and have children without significant limitations.

A diagnosis of Addison's disease is life-changing, but it doesn't have to be life-limiting. With modern treatment and proper self-management, the vast majority of people with Addison's disease lead full, active lives. The key is understanding your condition, being consistent with medication, and knowing how to handle situations that require extra cortisol.

Daily Life Considerations

After diagnosis, you may need a period of adjustment, both physically and emotionally. It can take time to find the optimal medication doses and to understand how the condition affects you personally. Many people initially feel fatigued even with treatment, though this typically improves over time.

Most daily activities can continue as normal. You can:

• Work in most professions
• Exercise and play sports (though you may need to adjust medication for intense activity)
• Travel (with proper preparation)
• Have children (pregnancy requires specialist care)
• Eat a normal diet (though adequate salt intake is important)

Always Carry Emergency Information

You should always carry:

• A steroid emergency card with your diagnosis, medication, and emergency instructions
• Medical ID jewelry (bracelet or necklace) stating you have Addison's disease
• Emergency hydrocortisone injection kit when traveling or in situations where medical care might not be immediately available

Inform Others About Your Condition

It's important that family members, close friends, and colleagues understand your condition and know what to do in an emergency. They should know:

• The signs of adrenal crisis
• How to administer emergency hydrocortisone
• That they should call emergency services immediately if you're unwell and unable to help yourself

Regular Medical Follow-Up

You'll need regular appointments with your endocrinologist or healthcare provider, typically 1-2 times per year once your condition is stable. These visits include:

• Review of symptoms and how you're managing
• Blood tests to check electrolytes and sometimes hormone levels
• Blood pressure monitoring
• Screening for related autoimmune conditions
• Medication adjustments if needed

Traveling with Addison's Disease

Travel is absolutely possible but requires planning:

• Carry a letter from your doctor explaining your condition and medications
• Pack medications in multiple bags (never put all in checked luggage)
• Bring extra supplies including emergency injection
• Know how to access medical care at your destination
• Consider time zone changes when timing medication doses

Can You Have Children with Addison's Disease?

Yes, women with Addison's disease can have healthy pregnancies and children. Pregnancy requires specialist endocrine care, as medication doses typically need to be increased in the third trimester and during delivery. The medications (hydrocortisone and fludrocortisone) are safe during pregnancy and breastfeeding. Fertility is usually not affected by Addison's disease itself, though associated autoimmune conditions may sometimes affect the ovaries.

Having Addison's disease does not prevent pregnancy, and with proper management, women with this condition can have healthy pregnancies and babies. However, pregnancy does require careful planning and specialized care.

If you're planning to become pregnant, inform your endocrinologist beforehand. During pregnancy, you'll be monitored by both your endocrinologist and a specialist obstetric team. Hydrocortisone doses typically need to be increased during the third trimester as the body's cortisol requirements increase. During labor and delivery, you'll receive intravenous hydrocortisone to handle the physical stress.

Both hydrocortisone and fludrocortisone are safe to take during pregnancy and while breastfeeding. These medications replace hormones that the body would normally produce, so they don't pose risks to the baby.

What Other Conditions Are Associated with Addison's Disease?

Because autoimmune Addison's disease often occurs alongside other autoimmune conditions, regular screening may be recommended for:

• Thyroid disease: Both underactive (hypothyroidism) and overactive (hyperthyroidism) thyroid conditions
• Type 1 diabetes
• Celiac disease
• Pernicious anemia (vitamin B12 deficiency)
• Primary ovarian insufficiency in women