Definition and Overview

Addison’s disease is a rare autoimmune disorder that occurs when the adrenal glands fail to produce sufficient amounts of steroid hormones, primarily cortisol and sometimes, aldosterone.

Cortisol is one of the body’s most important hormones with almost every cell containing receptors for it. It has far-reaching effects and is essential for many processes including metabolism and immune response. It helps control blood sugar levels, reduce inflammation, regulate metabolism, and assist in memory formation. Cortisol is best known for its crucial role in the “fight-or-flight” response in which the body gets a burst of energy and strength in preparation to what it perceives to be a threat or danger.

Aldosterone, on the other hand, plays an important role in cardiovascular health. It helps in the regulation of potassium and sodium levels in the body and in balancing the amount of electrolytes and fluids in the blood. It also plays a crucial role in controlling blood pressure.

Low cortisol and aldosterone levels often lead to a number of unpleasant symptoms as well as psychological and physical health issues that can drastically affect a patient’s quality of life.

Causes of Condition

In the majority of cases, Addison’s disease is the result of autoimmune polyglandular syndrome (APS), which causes the immune system to attack the outer layer of the adrenal cortex. APS is an inherited condition that develops when a child receives one changed AIRE gene (a protein coding gene) from each parent. Other than Addison’s disease, a patient with APS also develops other problems in other glands resulting in the development of hypogonadism (sex gland failure) and hypoparathyroidism (parathyroid glands fail to produce enough parathyroid hormone). Other features of APS include childhood-onset yeast infection, underdeveloped teeth enamel, keratoconjunctivitis (inflammation of the cornea and conjunctiva), chronic active hepatitis, and gastrointestinal problems.

Addison’s disease can also be caused by secondary adrenal insufficiency, which occurs when the pituitary gland fails to produce adrenocorticotropic hormone (ACTH) that stimulates the adrenal cortex to produce cortisol, among other hormones.

Rarely, the condition is caused by the following:

  • Tuberculosis

  • Cancer of the adrenal glands

  • Severe infections of the adrenal glands

  • Surgery on the adrenal glands

Addison’s disease is very rare, affecting roughly one in every 100,000 people. It can affect any person of any sex, age, or ethnicity but is commonly found in adults between 30 and 50 years old.

Key Symptoms

Addison’s disease can be very difficult to detect at first because its symptoms are not unique or similar to those produced by many other medical conditions. During the early stages, patients often complain of the following:

  • Fatigue

  • Increased craving for salty foods

  • Increased thirst

  • Irritability or depression

  • Muscle weakness

  • Unintentional weight loss

  • Frequent urination

If left untreated, the above symptoms can worsen gradually over months or years especially when patients are faced with significant emotional stress or develop other illnesses. When this happens, patients may experience the following:

  • Abdominal pain

  • Chronic exhaustion

  • Confusion

  • Diarrhoea

  • Difficulty concentrating

  • Fainting

  • Hyperpigmentation or darkening of skin colour

  • Irregular periods in women

  • Joint or back pain

  • Low blood pressure/blood sugar

  • Muscle cramps

  • Reduced sexual drive

  • Severe anxiety

  • Sores in the mouth

  • Vomiting

Patients with Addison’s disease are at risk of Addisonian crisis if they are severely dehydrated, develop a severe infection, or suffer from an injury that causes physical shock. The condition also occurs if patients receiving treatment for adrenal insufficiency are not taking the prescribed medications. Its symptoms include:

  • High potassium levels

  • Loss of consciousness

  • Low blood pressure

  • Low sodium

  • Pain in the legs, abdomen or lower back

  • Gastrointestinal problems, such as severe diarrhoea and vomiting, which could lead to dehydration

If left untreated, Addisonian crisis can lead to shock, seizures, and death.

Who to See and Types of Treatments Available

Addison’s disease is diagnosed with a blood test that measures sodium, cortisol, potassium, and ACTH levels as well as antibodies associated with Addison’s disease. This is usually followed by an ACTH stimulation test that measures how well the adrenal glands respond to adrenocorticotropic hormone, which stimulates the adrenal glands to produce cortisol. In patients with Addison’s disease, their output of cortisol in response to synthetic ACTH is either nonexistent or very limited. Doctors may also perform imaging tests, such as a computed tomography (CT) scan of the abdomen to visualise the adrenal glands and magnetic resonance imaging (MRI) scan of the pituitary glands if secondary adrenal insufficiency is suspected.

Addison’s disease is treated with life-long hormone replacement therapy that aims to correct cortisol and aldosterone levels. Patients are prescribed with oral corticosteroids and fludrocortisone that have to be taken daily to replace lost hormones. Such medications do not usually cause any side effects but when taken in excess of the prescribed dose for an extended period, patients may be at risk of insomnia, osteoporosis, and mood swings. In some cases, treatment of the condition also involves managing any underlying conditions, such as tuberculosis or adrenal gland cancer.

Many patients who regularly take their medications live normally and are able to continue with their normal diet and exercise routines. However, some still experience fatigue and low energy, especially if they are taking their medications late or if they miss a dose. They must see their endocrinologist regularly to monitor their progress and to determine if their medications have to be adjusted in order to achieve optimum results.


  • Stewart PM, Newell-Price JDC. The adrenal cortex. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 15.

  • Addison disease. Merck Manual Professional Version.

  • Adrenal insufficiency and Addison's disease. National Institute of Diabetes and Digestive Health and Kidney Disease.

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