Addison's disease

Definition

Addison’s disease is a slowly progressive disease which occurs when the cortex (outside) of the adrenal glands are not functioning correctly. Addison’s disease occurs when the secretion of the corticosteroid hormones (produced by the adrenal glands) fall below the requirements of the body.

The adrenal glands are two triangular glands situated on top of the kidneys. Each gland has two parts – the medulla (inside) and the cortex. The medulla produces the two hormones adrenaline and noradrenaline.

The cortex surrounds the medulla and is stimulated by the pituitary gland (situated in the brain) to produce three types of corticosteroid hormones. These affect carbohydrate metabolism (eg. cortisol), salt and water (electrolyte) metabolism (eg. aldosterone) and the sex glands (androgens and oestrogens).

Addison’s disease refers to what is called primary insufficiency of the adrenal glands. This means that it is not secondary to the use of steroid drugs.

Cause

Addison’s disease results from progressive destruction of the adrenal cortex, which must involve more than 90% of the glands before signs of adrenal insufficiency appear.

About 70% to 90% of cases are due to atrophy of the adrenal cortex from an unknown cause. The remainder result from destruction of the gland by diseases such as tuberculosis (TB), tumours or other disease processes.

Who gets it?

This is an uncommon condition affecting around four people out of every 100 000.

The disease occurs equally in each sex and in all age groups. It tends to become clinically apparent during metabolic stress and trauma.

There are no known risk factors for developing the disease.

Symptoms and signs

Addison’s initial description of the disease was of “…general languor and debility, remarkable feebleness of the heart’s action, irritability of the stomach and a peculiar change in the colour of the skin.” This summarises the main features of the disease as outlined by the doctor who first described the disease.

The onset of the illness is gradual with progressive tiredness and easy fatigability, weakness, loss of appetite, nausea and vomiting, weight loss, brown pigmentation of the skin and mucous membranes, low blood pressure and occasionally low blood sugar (hypoglycaemia).

The range of symptoms may vary depending on the duration and extent of adrenal hypofunction. It may simply be a complaint of chronic fatigue or fulminating shock associated with acute massive destruction of the glands called Waterhouse-Friderichsen syndrome.

Asthenia (loss of strength, debility) is the main symptom. Early in the disease it may be sporadic and most evident at times of stress. As adrenal function becomes more impaired, weakness progresses until the patient is continually tired, needing bed rest.

Increased pigmentation may be a prominent sign but is not always present. It commonly appears as a diffuse brown, tan or bronze darkening of both exposed and unexposed parts (such as the elbows or creases of the hand) and of areas normally pigmented (such as the areola of the nipple). Bluish-black patches may appear on the mucous membranes. Some people develop dark freckles and irregular areas where the skin loses pigmentation occur. As an early sign, patients may notice an unusually persistent tan following exposure to the sun.

Low blood pressure is common and in severe cases blood pressure may be 80/50 or less.

Problems with the gut are a common complaint. Symptoms may vary from mild loss of appetite and weight loss to severe nausea, vomiting, diarrhoea and ill-defined abdominal pain which can be severe.

Patients with adrenal insufficiency can suffer marked personality changes, usually in the form of excessive irritability and restlessness.

Some people find they have an enhanced sense of taste, smell and hearing. This is reversed with treatment.

Women frequently notice a loss of pubic and underarm (axillary) hair.

Diagnosis

Addison’s disease can only be diagnosed using specific investigations which determine the body’s ability to produce corticosteroids.

This is done by stimulating the adrenal glands using a hormone called ACTH (adrenal corticotrophic hormone) and seeing how much corticosteroid they can produce.

Treatment

All patients with Addison’s disease need specific hormone replacement and patients need to be educated about their disease.

Since the adrenal gland affects three general classes of hormone of which two, glucocorticoids (affecting carbohydrate metabolism) and mineralocorticoids (affecting salt and water metabolism) are of primary clinical importance, replacement therapy should correct both deficiencies.

Cortisone (or cortisol) is the mainstay of treatment. Most patients take between 12.5 - 50mg daily in divided doses. This should be taken with meals since the drug can cause gastric irritation.

Some people suffer from irritability, insomnia and mental excitement after treatment is started. In these cases, the dose should be reduced. Other reasons for smaller amounts of glucocorticoids are high blood pressure, diabetes or active TB.

As the recommended amount of cortisone does not replace the mineralocorticoid component of the adrenal gland, a supplementary hormone is usually needed. This is given in the form of 0.05 - 0.1mg of fludrocortisone. Patients also need to take in adequate amounts of sodium (3 - 4g a day).

Complications of glucocorticoid therapy are rare in the dosage used in the treatment of Addison’s disease.

Complications of mineralocorticoid therapy occur more frequently and include low potassium, oedema (swelling of the extremities), heart enlargement and even congestive cardiac failure due to salt retention.

All patients with adrenal insufficiency should carry medic alert tags to show they have Addison’s disease. The disease affects how they should be managed if they suffer any trauma or illness in which they collapse and are unable to communicate with emergency personnel.

There are some special problems associated with treatment for Addison’s disease. During periods of other illness, the dose of cortisone should be increased. This is also the case before surgery or dental extractions.

Patients also need to increase the dose of fludrocortisone and to add excess salt to their otherwise normal diet during periods of excessive exercise, during extremely hot weather and when they experience tummy upsets.

Outcome

With continued substitution therapy, the prognosis is excellent and a patient with Addison’s disease should be able to lead a normal life.

When to see your doctor

Any excessive tiredness or weakness should always be investigated since it can be a sign of serious illness. This is often the first sign of Addison’s disease.

If you already have Addison’s disease, you need to consult your doctor about your drug regime if you have any other illness or are suffering from particular physical stresses.

Reviewed by Dr H. Neethling, MBChB, Hons B.Sc (Pharm), M.Med (Int)