Addison's Disease - Symptoms & Causes

What is Addison's disease?

Addison's disease, also known as primary adrenal insufficiency disorder, is a rare adrenal gland disease. Its worldwide incidence is only 6 out of 1 million, primarily affecting females in their 30s to 50s.

Adrenal glands are two small, triangular glands located above the kidneys. Like other glands, they produce hormones, particularly cortisol and aldosterone. Addison's disease affects the cortex (the outer layer) of the adrenal glands, stopping the normal production of these hormones. As a result, the patient's body encounters deficiency of the adrenal hormones, followed by a series of physiological reactions.

Types of adrenal insufficiency

There are 2 types of adrenal insufficiency: primary and secondary. The difference is in their disease processes and hormones affected.

• Primary adrenal insufficiency (Addison's disease). It is caused by the direct destruction of the adrenal glands. The most common aetiology is autoimmune diseases, meaning the body's immune cells attack their own's body tissue.

• Secondary adrenal insufficiency. It may happen in people taking an extended period of steroids. Cortisol itself is a steroid hormone that is naturally produced by the adrenal glands. When there are external steroids that are like cortisol, the body reacts by the pituitary gland (the major command centre for hormones, which lie just beneath our brain) reducing production of ACTH – the hormone that will act on the adrenal gland to command it to produce cortisol. As such, if ACTH is suppressed, the adrenal glands go to sleep and stop producing cortisol.

What are the symptoms of Addison's disease?

People with Addison's disease may present with fatigue, body weakness, weight loss, nausea, vomiting, abdominal pain, dizziness, fast heart rate, low blood pressure and irregular periods in females.

Another distinct feature of Addison's disease is hyperpigmentation (dark spots), commonly at the palmar creases, nail beds, knuckles, gum, edge of lips, elbows, back of neck, and area around the nipples.

Symptoms of Addison's disease are often non-specific and progress silently, making them difficult to be identified.

Therefore, many people are unaware that they have Addison's disease until the hormone levels are low enough to cause severe symptoms. This condition is called an adrenal crisis, a potentially lethal emergency that requires immediate medical attention.

What causes Addison's disease?

Any conditions that damage the adrenal gland can cause Addison's disease. They can be classified into several groups as below:

• Autoimmune: Isolated autoimmune destruction of the adrenal gland. Sometimes, the adrenal gland is not the only gland that is affected (polyglandular autoimmune syndromes)
• Infections: E.g. sepsis (severe blood infection), tuberculosis (a type of bacterial lung infection), cytomegalovirus and HIV infection
• Adrenal bleeding: This may happen during disseminated intravascular coagulation (widespread abnormal blood clotting in the vessels throughout the body), trauma, cancers and Waterhouse-Friderichsen syndrome (bleeding of the adrenal glands due to severe bacterial infections)
• Genetic: Adrenal anatomical abnormalities since birth, usually due to genetic defects
• Drugs: Ketoconazole (an antifungal medication), etomidate (a sedative medication)
• Cancer: E.g. lymphoma of the adrenal glands

What are the risk factors for Addison's disease?

The risk of Addison's disease increases when one has these coincident autoimmune diseases:

• Type I diabetes, also known as juvenile diabetes or insulin-dependent diabetes
• Hypoparathyroidism, a condition where the parathyroid hormone is low
• Hypopituitarism, a condition where there is insufficient production of pituitary hormones
• Pernicious anaemia, an autoimmune cause of anaemia due to vitamin B12 or folate deficiency
• Graves' disease, an immune system disorder that results in hyperthyroidism (excess production of the thyroid hormones)
• Hashimoto’s thyroiditis, an immune system disorder that results in hypothyroidism (deficient production of the thyroid hormones)
• Dermatis herpetiformis, a skin condition related to celiac disease
• Vitiligo, a skin condition presenting with generalised white skin patches due to loss of skin pigment cells
• Myasthenia gravis, a disorder with muscle weakness including eye muscles

What are the complications of Addison's disease?

Addison's disease can turn into an adrenal crisis, which is an acute, severe life-threatening event. Adrenal crisis may present with­:

• Low blood pressure
• Shock
• Low blood sugar
• Acute cardiovascular decompensation
• Death

In long-term Addison's disease, depleted hormones can impact all body systems, causing significant complications that include:

• Higher risk of death due to infections, cancer, and cardiovascular causes
• Neurological conditions due to persistent low blood sugar
• Cushing syndrome if there is excessive steroid replacement
• Stunted growth in children
• Ovarian dysfunction in women

How do you prevent an adrenal crisis?

Prevention is of utmost importance, considering the lethal complications of ­ adrenal crisis. Here are some tips:

• Take your medication at the correct dosing and regular timing.
• Take a higher dose of medicine (steroid) in specific situations such as illness, accidents, operations including dental and medical procedures, more strenuous activities than your regular exercises, and severe psychological stress such as grief. Consult your doctor to know when you must increase your medication doses.
• Ensure the proper injection technique of emergency medications if you are prescribed this.
• Recognise early symptoms that signal an adrenal crisis.
• Always bring spare medications when travelling.
• Always carry a medical notification card or wear a medical alert bracelet or necklace if possible.