Addison's disease

Symptoms Of Addison's Disease

Addison’s disease is a hormonal disorder with an array of symptoms. These include:

• Tiredness and fatigue

• Loss of appetite

• Craving for salt

• Nausea, vomiting

• Abdominal pain

• Dizziness

• Pain in the muscles

• Diarrhea

• Loss of consciousness

• Constipation

• Increased pigmentation

• Loss of weight

• Hypotension (low BP)

• Anemia

• Vitiligo (a disease that causes loss of skin color in patches)

Note: Sometimes the symptoms of Addison's disease appear suddenly. This is known as the Addisonian crisis. It is a life-threatening situation that results in low blood pressure, low blood levels of sugar, and high blood levels of potassium. 

Causes Of Addison's Disease

Addison's disease is caused by damage to the adrenal glands that sit just above the kidneys resulting in adrenal insufficiency. Causes of adrenal insufficiency based on the type includes:

Primary adrenal insufficiency

It occurs when the adrenal glands are damaged and don’t make enough of the hormones cortisol and aldosterone. The major causes of primary adrenal insufficiency include:

Autoimmune disorders: These are conditions in which your immune system attacks your adrenal glands. These include:

• Autoimmune polyendocrinopathy (an inherited condition affecting major organs)

• Candidiasis

• Ectodermal dysplasia ( a genetic disorder affecting the development of the teeth, hair, nails, and sweat glands)

• Autoimmune thyroiditis 

• Type 1 diabetes 

• Pernicious anemia

• Vitiligo or alopecia

Infections: These can cause an adrenal crisis due to decreased cortisol leading to severe complications. Infections that can cause primary adrenal insufficiency include:

• Sepsis

• Tuberculosis

• HIV

• Cytomegalovirus infections

• Fungal infections

• Syphilis
  
  

Adrenal hemorrhage: Bilateral adrenal hemorrhages can be due to DIC (Disseminated Intravascular Coagulation, a serious disorder in which the proteins that control blood clotting become overactive), trauma, meningococcemia (infection in the bloodstream). 

Note: An Adrenal crisis due to meningococcemia is known as the Waterhouse-Friderichsen syndrome and is more common in children and patients without a spleen.

• Infiltration: This can be due to cancer and abnormal growths (tumors) that can cause primary adrenal insufficiency.

• Drugs: Certain drugs can cause adrenal insufficiency by blocking cortisol synthesis. They include:
  
  

• Blood thinners

• Glucocorticoids

• Antifungal agents

Secondary adrenal insufficiency

This starts when the pituitary gland doesn’t make enough of the hormone ACTH (adrenocorticotropin) resulting in decreased cortisol levels. Causes of secondary adrenal insufficiency include:

• Tumors

• Medications like corticosteroids

• Family history

• Trauma or injury to the brain

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Risk Factors For Addison's Disease

Adrenal insufficiency causes Addison’s disease. There are certain factors that can increase your chances of developing this insufficiency. They include:

1. Type I diabetes

The risk of developing Addison’s disease is higher in those suffering from type 1 diabetes.

Type 1 diabetes also known as juvenile diabetes is a chronic condition in which the pancreas produces little or no insulin.

Note: Type I Diabetes is called Juvenile diabetes because it affects the younger population. It is an autoimmune condition causing the destruction of the cells of the pancreas.

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2. Hypoparathyroidism

It is a condition in which the parathyroid glands don't produce enough parathyroid hormone. Though a rare disorder, affected individuals have been associated with Addison's disease.

3. Hypopituitarism

Your pituitary gland is a small, pea-sized gland located at the base of your brain. It produces and releases several hormones that help carry out important bodily functions. Hypopituitarism leads to a deficiency of one or more of the pituitary hormones and can lead to adrenal insufficiencies.

4. Pernicious anemia

Pernicious anemia is caused by Vitamin B12 deficiency and is associated with primary adrenal insufficiency.

5. Testicular dysfunction

It is a condition in which the testicles cannot produce enough sperm or male hormones, such as testosterone. This can be caused by autoimmunity, which in turn increases the chances of getting Addison’s disease.

6. Grave’s disease

It is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Grave’s disease and Addison's disease are linked with a strong auto-immune basis.

Note: Individuals with Graves' disease and Addison's simultaneously are at risk of incipient adrenal crisis.

7. Chronic thyroiditis

It is a condition that causes swelling of the thyroid gland. It often results in reduced thyroid function, thus increasing the risk for the development of Addison’s disease.

8. Dermatitis herpetiformis

Commonly known as celiac disease, this is a chronic condition with intense itching, and blisters all over the skin. Individuals with this disorder are at a higher risk of developing Addison’s disease and other autoimmune conditions.

9. Vitiligo

Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus.

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10. Myasthenia gravis

It is an autoimmune disorder in which antibodies destroy the communication between nerves and muscles, resulting in weakness of the skeletal muscles. This condition is rarely associated with Addison’s disease.

11. Medications 

Certain drugs like Ketoconazole and Etomidate can cause adrenal insufficiency by blocking cortisol synthesis. 

12. Other risk factors

• Sarcoidosis: It is characterized by the growth of tiny collections of inflammatory cells, (known as granulomas) in the body.

• Lymphoma: Cancer of the lymphatic system that includes lymph nodes, spleen, thymus gland, and bone marrow.

• Congenital adrenal hyperplasia: A group of genetic disorders affecting the adrenal gland.

• Adrenoleukodystrophy: It is a type of genetic condition that damages the membrane protecting the nerve cells in the brain.

Diagnosis Of Addison's Disease

Diagnosing Addison’s disease can be very crucial in deciding the treatment. The diagnosis must include detailed history along with a physical examination to evaluate the signs and symptoms. 

Apart from this, the diagnosis is established by the following:

1. Laboratory tests

These consist of blood tests to check for any imbalance in the hormonal levels. Tests include:

• Serum cortisol: A low cortisol level (< 3 mcg/dL) confirms the diagnosis of adrenal insufficiency.

• ACTH stimulation test: This test measures how well the adrenal glands respond to adrenocorticotropic hormone (ACTH). The ACTH level is markedly elevated in primary adrenal insufficiency.

• Serum renin and aldosterone levels: This test is done to determine whether a mineralocorticoid deficiency is present.

• Anti–21-hydroxylase antibodies: These serve as the markers of autoimmune destruction of the adrenal gland. 

• Other tests: 

  • Serum electrolytes

  • Random blood glucose test

  • Serum calcium

  • TSH (Thyroid stimulating hormone ) test

  • Complete blood count (CBC)
    
    

Imaging tests

These tests are done to have a better look at the adrenal gland. These include:

• Abdominal computed tomography (CT): It is done in a suspected case of adrenal hemorrhage.

• Magnetic resonance imaging (MRI): MRI of the hypothalamic-pituitary region should be obtained if ACTH is inappropriately low in the presence of cortisol deficiency. 

• Chest radiograph: This test may be useful to diagnose tuberculosis associated with Addison’s disease

Additional tests

• PPD test: This is a skin test that should be performed to evaluate for tuberculosis. 

• Plasma's very long-chain fatty acid profile: This test is done in cases where damage to the nerves is suspected.

• Electrocardiography (ECG): ECG is done to check for hyperkalemia (increased potassium levels) caused by aldosterone hormone deficiency in Addison’s disease.

• Histology: It is useful to investigate infiltrative causes of adrenal insufficiency.
  
  

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Prevention Of Addison's Disease

There is no way to prevent Addison’s disease, but the condition can be well-managed to prevent the Addisonian crisis. Certain useful tips include:

• Talk to your doctor if are always tired or are losing weight without even trying

• Understand what is an adrenal shortage

• Know what to do when you're sick or in case of an emergency

• Get enough sleep

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• Have optimum salt intake in your diet 

• Try to have a healthy lifestyle

• Exercise regularly

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• Eat a well-balanced nutritious diet

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• Avoid red meat, foods with preservatives, aerated drinks, and sugar

• Drink alcohol in moderation

• Quit smoking.

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Specialist To Visit

Doctors that can help diagnose and curate an appropriate treatment plan for the management of Addison’s disease include:

• General physician

• Endocrinologist

An endocrinologist is a doctor who treats conditions of the endocrine glands.

When to see a doctor?

Seek emergency treatment if you notice the following:

• Extreme weakness

• Intense pain

• Unstable or changes in the heart rate or blood pressure

• Temperature higher than 101 F

• Persistent hypotension (low BP)

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Treatment Of Addison's Disease

Timely treatment of Addison’s disease is very crucial, as negligence can lead to an Addisonian crisis that can be life-threatening. The treatment mainly consists of hormone replacement therapy that corrects the levels of steroid hormones. It includes:

1. Hormone replacement therapy

• Glucocorticoid replacement: The medications commonly used are:

• Hydrocortisone
• Prednisone 
• Dexamethasone

 During this regime, clinical symptoms and plasma ACTH are monitored as required. 

• Mineralocorticoid replacement: Fludrocortisone is the most commonly used drug during this regime. During this treatment, it is important to monitor blood pressure as well as pulse, edema, and serum potassium levels

• Androgen replacement: Dehydroepiandrosterone (DHEA) is usually the drug of choice. This therapy is given only in women for psychological well-being, if needed, after optimal glucocorticoid and mineralocorticoid replacement

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2. Management of adrenal crisis

This is a life-threatening condition that needs immediate treatment. The management consists of the following:

• Intravenous (IV) infusion of isotonic saline or 5% dextrose as early as possible

• Analysis of serum electrolytes, glucose, and routine measurement of plasma cortisol and ACTH.

• IV Hydrocortisone and due correction of any ongoing electrolyte abnormalities

3. Treatment during pregnancy

Pregnant patients with primary adrenal insufficiency should be monitored for clinical symptoms and signs of glucocorticoid over- and under-replacement (normal weight

gain, fatigue, low or high BP, increased blood sugar) with at least one review per trimester. The drugs used are:

• Hydrocortisone

• Prednisolone

• Dexamethasone

4. Treatment during childhood

In children with primary adrenal insufficiency, treatment with hydrocortisone in three or four divided doses is recommended. Fludrocortisone is recommended in children with primary adrenal insufficiency along with aldosterone (a hormone that helps regulate your blood pressure) deficiency.

Home care For Addison's Disease

Addison’s disease requires lifelong hormone replacement therapy. Along with medications there are certain home care tips that can help manage your condition better. These include:

1. Eating a supportive diet

Some people with Addison’s disease may have low aldosterone levels leading to low sodium and high amounts of potassium. Eating a diet that can balance out this can be very beneficial.

Foods to eat

• Grain products

• Eggs

• Cheese

• Milk

• Yogurt

• Broccoli

• Tofu

• Fortified cereal

• Chicken

• Tuna

• Canned beans

Foods to avoid

• Coffee

• Green tea

• Black tea

• Excessive alcohol

• Too many bananas and oranges

• Salt substitutes

2. Adding that extra salt

Individuals with Addison’s disease tend to crave salt due to low aldosterone levels, The best choice of sodium-rich foods is foods like eggs, cheese, salted nuts and seeds, and poultry. 

3. Managing stress

Stress can hamper the treatment of Addison’s disease by decreasing glucocorticosteroid secretions. Make time to relax, every day and practice slow, deep breathing to manage your stress levels. 

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4. Giving importance to supplements

People who take medicines to replace cortisol may also need plenty of calcium and vitamin D. Taking supplements like adaptogens and certain vitamins can be very useful. Consult your doctor or dietitian before starting these supplements.

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Complications Of Addison's Disease

The major complication of Addison’s disease is acute adrenal insufficiency or Addisonian crisis. This generally occurs when your body is stressed mainly due to an illness, fever, surgery, or dehydration. If an Addisonian crisis is not treated, it can lead to the following complications:

• Shock

• Seizures

• Severe abdominal pain

• Extreme weakness

• Low blood pressure

• Kidney failure

• Coma

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COVID-19 infection can cause adrenal hemorrhage leading to primary and secondary adrenal insufficiencies.
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Alternative Therapies For Addison's Disease

Certain alternative therapies have shown good results in managing Addison's disease along with conventional treatment. These include:

Naturotherapy

This is a method to treat illnesses or conditions using natural foods, massages, and other techniques instead of artificial medications. The most commonly used herb is Ashwagandha, which helps to restore optimal health by maintaining energy levels and immunity function. 

Salt substitution therapy

Salt substitutes replace part of the sodium chloride in regular salt with potassium chloride. This therapy can maintain the expected level of sodium chloride and other elements found to be deficient in these individuals.

Regenerative therapy

This therapy is beneficial for Addison’s disease as it uses the application of stem cells. Stem cells are cells from which all other cells with specialized functions are generated. They have the potential to repair and restore function in damaged body tissues or organs. 

Living With Addison's Disease

Diagnosis of Addison’s disease may come as a shock and the fact that it requires lifelong treatment can be overwhelming. But, this condition can be well managed and individuals with this disorder can live their life to the fullest. However, there are certain things to remember if you have Addioson’s disease. These include:

1. Understand your condition

Knowing everything about your illness can be very beneficial, especially in managing an emergency situation.

Also, managing stress and learning to inject your medications can help you be independent.

2. Have a medical alert bracelet/necklace

It is an emergency medical information card on your phone or inside your wallet, and prefilled syringes containing 4 mg of dexamethasone in 1 mL saline. An emergency card and medical alert identification helps emergency care providers know what kind of care you might need. 

3. Keep extra medicines handy

Missing out on even a single dose can be dangerous, so always keep your medications stocked up. Also, have a small supply at work and with you when you travel. 

4. Get yearly checkups

See your doctor at least once a year. Your doctor may recommend yearly screening for autoimmune diseases, and monitoring your hormone levels. If you have problems with your medication, your provider might need to change the doses or time.

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