Addison's Disease (Primary Adrenal Insufficiency)

What the adrenal glands do

The two adrenal glands sit on top of the kidneys. Their outer layer (cortex) makes:

• Cortisol: the stress hormone. It maintains blood pressure, blood sugar, energy and the response to illness and injury.
• Aldosterone: controls salt and water balance by making the kidneys keep sodium and excrete potassium.
• Adrenal androgens (DHEA): minor sex hormones.

In Addison's disease, more than 90% of the cortex is destroyed before symptoms appear. The pituitary responds to low cortisol by making more ACTH (adrenocorticotropic hormone). ACTH comes from the same precursor as melanocyte-stimulating hormone, which is why skin darkens.

Symptoms

Symptoms usually come on over months and are easily mistaken for other problems:

• persistent fatigue, weakness and low mood
• loss of appetite and weight loss
• nausea, vomiting, belly pain and diarrhea
• dizziness or fainting on standing, from low blood pressure
• salt craving, such as eating salt from the packet
• muscle and joint aches
• hyperpigmentation: darkening of skin creases, scars, knuckles, elbows, lips and gums
• low blood sugar, especially in children
• loss of body hair and libido in women

Adrenal crisis

An adrenal crisis is a medical emergency caused by a sudden lack of cortisol. It is often the way Addison's disease is first discovered, or happens in known patients during an infection, vomiting illness, injury or surgery. Signs include severe vomiting, belly pain, confusion, extreme weakness, very low blood pressure and collapse. Without treatment it can be fatal within hours. Treatment is immediate injection of hydrocortisone, IV fluids and glucose.

Causes

About half of people with autoimmune Addison's disease have another autoimmune condition, such as hypothyroidism, type 1 diabetes, vitiligo or pernicious anemia. These clusters are called autoimmune polyendocrine syndromes.

Primary vs secondary adrenal insufficiency

Addison's disease is primary: the adrenal glands themselves fail. Secondary adrenal insufficiency comes from the pituitary (low ACTH) or, most commonly, from stopping long-term steroid medicines suddenly. In secondary cases, aldosterone is usually preserved and the skin does not darken.

Diagnosis

• Blood tests: low sodium (hyponatremia), high potassium, sometimes low glucose and raised calcium
• Early morning cortisol: a very low level strongly suggests adrenal insufficiency
• ACTH: high in Addison's disease
• ACTH (Synacthen) stimulation test: cortisol is measured before and 30 to 60 minutes after an injection of synthetic ACTH. A failure to rise confirms adrenal insufficiency.
• Renin and aldosterone: high renin with low aldosterone
• 21-hydroxylase antibodies: confirm autoimmune cause
• CT of the adrenals if antibodies are negative

In suspected adrenal crisis, treatment is given immediately after drawing blood, without waiting for results.

Treatment

Daily replacement

• Hydrocortisone (or prednisolone) to replace cortisol, usually in 2 to 3 daily doses mimicking the body's natural rhythm, with the largest dose on waking.
• Fludrocortisone to replace aldosterone, adjusted by blood pressure, salt craving and renin levels.
• Unrestricted salt intake.
• DHEA is sometimes offered to women with low wellbeing or libido.

Sick-day rules

Because the body cannot raise its own cortisol under stress:

• Double or triple the hydrocortisone dose during fever, infection or illness requiring bed rest, as directed by your endocrinologist.
• Inject emergency hydrocortisone if vomiting or unable to take tablets, then seek emergency care.
• Extra cover is needed for surgery, dental procedures, childbirth and heavy exertion.
• Carry a steroid emergency card and wear a medical ID bracelet.
• Keep an emergency injection kit at home and when traveling, and teach family how to use it.

Living with Addison's disease

With correct replacement and crisis planning, most people work, exercise, travel and have children normally. Regular endocrine reviews monitor symptoms, blood pressure, electrolytes and bone health, and screen for other autoimmune conditions. Over-replacement with steroids can cause weight gain and bone thinning, so the lowest effective dose is used.

Frequently asked questions

What are the first symptoms of Addison's disease?

Early symptoms are usually tiredness, weakness, poor appetite, weight loss and dizziness on standing. Many people crave salt and develop darker skin, particularly in creases, scars and gums. Nausea and belly pain are common. Symptoms are gradual and easily attributed to stress or other causes.

What causes Addison's disease?

In most developed countries, Addison's disease is autoimmune: the immune system attacks the adrenal glands. Worldwide, tuberculosis is a major cause. Other causes include infections, bleeding into the adrenals, cancer spread, genetic conditions and surgical removal of both glands.

What is an adrenal crisis?

An adrenal crisis is a life-threatening drop in cortisol, often triggered by infection, vomiting, injury or surgery. It causes severe vomiting, belly pain, confusion, very low blood pressure and collapse. It needs an immediate hydrocortisone injection and emergency care.

Is Addison's disease life-threatening?

Untreated, it can be, mainly through adrenal crisis. With daily hormone replacement and correct sick-day rules, people with Addison's disease have a near-normal life expectancy. Education on increasing doses during illness and carrying an emergency injection is essential.

Can Addison's disease be cured?

No. The adrenal damage in Addison's disease is permanent, so hormone replacement is lifelong. However, replacement therapy is effective, and most people feel well and lead full, active lives once their doses are optimized.