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 and vomiting
• Abdominal pain
• Dizziness
• Pain in the muscles
• Diarrhea
• Loss of consciousness
• Constipation
• Increased pigmentation
• Loss of weight
• Hypotension (low blood pressure)
• Anemia
• Vitiligo (a condition 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 sugar levels, and high potassium levels.

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 include:

Primary adrenal insufficiency

It occurs when the adrenal glands are damaged and do not produce enough of the hormones cortisol and aldosterone. The major causes of primary adrenal insufficiency include:

• Autoimmune disorders: Conditions in which the immune system attacks the adrenal glands, including:
  • 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 disseminated intravascular coagulation (DIC), trauma, or meningococcemia (infection in the bloodstream). Note: An adrenal crisis due to meningococcemia is known as 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, including:
  • Blood thinners
  • Glucocorticoids
  • Antifungal agents

Secondary adrenal insufficiency

This starts when the pituitary gland does not produce 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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Adrenal insufficiency causes Addison’s disease. There are certain factors that can increase your chances of developing this insufficiency. They include:

• 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. Know more about Type 1 diabetes
• 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.
• 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.
• Pernicious anemia: Pernicious anemia is caused by Vitamin B12 deficiency and is associated with primary adrenal insufficiency.
• 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.
• 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.
• 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.
• 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.
• Vitiligo: Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus. Wondering what exactly is vitiligo? Read about these 4 facts about vitiligo that can help you understand this condition better.
• 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.
• Medications: Certain drugs like Ketoconazole and Etomidate can cause adrenal insufficiency by blocking cortisol synthesis.
• 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.

Diagnosing Addison’s disease is crucial for determining appropriate treatment. The diagnosis must include a detailed history and a physical examination to evaluate the signs and symptoms.

The diagnosis is established by the following:

• Laboratory tests: These consist of blood tests to check for hormonal imbalances. 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 determines whether a mineralocorticoid deficiency is present.
• Anti–21-hydroxylase antibodies: These serve as 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 provide a better view of the adrenal gland and include:
• Abdominal computed tomography (CT): This is performed in suspected cases 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 for diagnosing tuberculosis associated with Addison’s disease.
• Additional tests:
• PPD test: A skin test performed to evaluate for tuberculosis.
• Plasma very long-chain fatty acid profile: This test is conducted when nerve damage is suspected.
• Electrocardiography (ECG): ECG is performed to check for hyperkalemia (increased potassium levels) caused by aldosterone hormone deficiency in Addison’s disease.
• Histology: This is useful for investigating infiltrative causes of adrenal insufficiency.

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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 you are always tired or losing weight without trying.
• Understand what an adrenal shortage is.
• Know what to do when you're sick or in case of an emergency.
• Get enough sleep.
• Have optimum salt intake in your diet.
• Try to maintain a healthy lifestyle.
• Exercise regularly.
• Eat a well-balanced nutritious diet.
• Avoid red meat, foods with preservatives, aerated drinks, and sugar.
• Drink alcohol in moderation.
• Quit smoking.

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Timely treatment of Addison’s disease is 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. It is important to monitor blood pressure, pulse, edema, and serum potassium levels during this treatment.
   • Androgen replacement: Dehydroepiandrosterone (DHEA) is usually the drug of choice. This therapy is given only to women for psychological well-being, if needed, after optimal glucocorticoid and mineralocorticoid replacement.
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 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 also recommended in children with primary adrenal insufficiency along with aldosterone deficiency.

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 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 choices of sodium-rich foods include eggs, cheese, salted nuts and seeds, and poultry.

3. Managing stress

   Stress can hinder 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.

4. Giving importance to supplements

   People who take medications 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.

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

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

• Naturotherapy: This method treats illnesses or conditions using natural foods, massages, and other techniques instead of artificial medications. The most commonly used herb is Ashwagandha, which helps restore optimal health by maintaining energy levels and immune function.
• Salt substitution therapy: Salt substitutes replace part of the sodium chloride in regular salt with potassium chloride. This therapy can maintain the expected levels 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.

Diagnosis of Addison’s disease may come as a shock, and the fact that it requires lifelong treatment can be overwhelming. However, this condition can be well managed, allowing individuals to live their lives to the fullest. There are certain things to remember if you have Addison’s disease:

• Understand your condition: Knowing everything about your illness can be very beneficial, especially in managing emergency situations. Managing stress and learning to inject your medications can help you be independent.
• Have a medical alert bracelet/necklace: This should include an emergency medical information card on your phone or inside your wallet, along with prefilled syringes containing 4 mg of dexamethasone in 1 mL saline. An emergency card and medical alert identification help emergency care providers understand what kind of care you might need.
• Keep extra medicines handy: Missing even a single dose can be dangerous, so always keep your medications stocked up. Also, maintain a small supply at work and while traveling.
• 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 experience issues with your medication, your provider might need to adjust the doses or timing.

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