What is adrenal insufficiency?
Adrenal insufficiency is a disorder which reduces the
production of adrenal hormones. It can take several
- Primary adrenal insufficiency: there is a problem with the adrenal glands themselves
- Central adrenal insufficiency: there is a problem with the hypothalamus (tertiary) or with the pituitary gland (secondary)
- Adrenal insufficiency caused by the use of medication (also known as steroid-induced adrenal insufficiency): there is a problem with the hypothalamus, the pituitary gland and the adrenal glands because of medication that contains cortisol or synthetic forms of cortisol.
What causes adrenal insufficiency?
Primary adrenal insufficiency is caused by damage occurring to the adrenal glands. Addison’s disease is the most common cause of primary adrenal insufficiency. In the case of Addison’s disease, the adrenal glands have usually been damaged by an inflammation of the adrenal glands caused by an autoimmune disease. When someone has an autoimmune disease, that person’s body produces antibodies which can lead to inflammation of a bodily organ; as a result that organ no longer functions properly. Other causes of primary adrenal insufficiency are infections, benign or malignant tumours, severe bleeding or an operation to remove the adrenal glands.
Central adrenal insufficiency can be caused by any disorder, injury or operation that damages the hypothalamus or the pituitary gland. In some rare cases, primary and central adrenal insufficiency can also be caused by a predisposition or can be part of a genetic syndrome.
Adrenal insufficiency caused by taking medication (steroidinduced adrenal insufficiency) occurs as a result of taking medication that contains cortisol or synthetic forms of cortisol. These substances are used in many different sorts of medication, including creams, ointments or shampoos, injections, inhalers for lung diseases and tablets. These types of medication suppress the activity of the hypothalamus, the pituitary gland and the adrenal glands, and lead to adrenal insufficiency.
How frequently does adrenal insufficiency occur?
There are no exact figures to show how frequently adrenal insufficiency occurs in the Netherlands. In the case of primary adrenal insufficiency, estimates range from 93 to 140 per million; this means that there are an estimated 1571 to 2366 people in the Netherlands with primary adrenal insufficiency. In the case of secondary adrenal insufficiency, estimates range from 125 to 280 per million; this means that there are an estimated 2100 to 4700 people in the Netherlands with secondary adrenal insufficiency. Steroidinduced adrenal insufficiency is the most common cause of adrenal insufficiency, but no precise figures are known about how frequently it occurs in the Netherlands.
What are the consequences of adrenal insufficiency?
In the case of primary adrenal insufficiency, the body has a shortage of glucocorticoids (cortisol), mineralocorticoids (aldosterone) and the hormone DHEA.
In the case of central adrenal insufficiency, the body has a shortage of glucocorticoids (cortisol) and androgens, although aldosterone is still produced. There is sometimes a shortage of other hormones with central adrenal insufficiency as well, including thyroid hormone, growth hormone or sex hormones. The disease is then known as hypopituitarism, which means that the pituitary gland is not functioning properly (or panhypopituitarism if it doesn’t produce any hormone at all).
The most common symptoms of adrenal insufficiency are tiredness, weakness, weight loss, nausea, vomiting, feeling gloomy, low blood pressure and pain in the muscles and joints. People who suffer from primary adrenal insufficiency also often experience a conspicuous craving for salt and a brown discoloration of the skin and the oral mucous membrane or the gums. The symptoms can exist for a long time before the condition is diagnosed. Sometimes, an adrenal insufficiency can present itself as an adrenal crisis. If that happens, the patient usually has severe forms of the symptoms mentioned above and may be extremely confused; it is not uncommon for the patient to go into a coma. If treatment is not given in time, a crisis of this nature can be fatal. An adrenal crisis usually coincides with illness or stress.
Despite treatment, the symptoms can sometimes persist. It is impossible to predict which symptoms this will be, or how severe they will be; everyone is different. They can, however, affect the quality of the patient’s life. People who have Addison’s disease can also develop other autoimmune diseases. Examples include: thyroid problems, diabetes, premature menopause, vitiligo (patchy loss of skin pigment), or a shortage of vitamin B12.
Tests and diagnosis
How is adrenal insufficiency diagnosed?
First of all, it is necessary to check whether the person in question is taking any medication that contains cortisol or a synthetic form of cortisol. This is, in fact, the most common cause of adrenal insufficiency and in that case efforts will be made to reduce the medication. The adrenal glands can usually return to normal functioning after a short while. If the person is not taking any medication of this type, tests will be done to measure the level of cortisol in the body. A low cortisol level can be discovered if the blood is tested early in the morning; if the cortisol level is very low, this indicates adrenal insufficiency.
A further test is quite often necessary, because the level of cortisol in the blood may not provide a clear indication. That test is called an ACTH test. ACTH hormone is administered either by infusion or via an injection into muscle tissue (IM). The cortisol level in the blood will then be tested at set times. If the cortisol level does not rise noticeably after ACTH is administered, this is a sign of adrenal insufficiency.
Further tests will then be carried out to determine the underlying cause of the adrenal insufficiency. In the case of primary adrenal insufficiency, there is a very elevated level of the hormone ACTH in the body. Quite often, other abnormalities will also be seen in the blood, such as reduced aldosterone, a high renin level and reduced DHEA or DHEAS level. Sometimes a low sodium level and a high potassium level is found in the blood. That will prompt tests to check for the presence of antibodies working against the adrenal glands. If there is a raised level of those antibodies, this will be an indication of Addison’s disease. If no antibodies are discovered, a CT scan of the adrenal glands will be carried out. This will make it possible to check for the presence of calcification (often seen in patients with tuberculosis), bleeding, tumours or other abnormalities of the adrenal glands. People with central adrenal insufficiency have a normal or reduced level of ACTH. Blood tests can show whether there is also a shortage of other hormones. If central adrenal insufficiency is suspected, an MRI scan of the pituitary gland will be carried out to check whether there is a tumour present, any inflammation or bleeding.
How is adrenal insufficiency treated?
Primary adrenal insufficiency is treated with hydrocortisone or cortisoneacetate (to replace cortisol) and fludrocortisone (to replace aldosterone). Sometimes, DHEA (dehydroepiandrosterone) is given as well. Central adrenal insufficiency is treated with hydrocortisone or cortisoneacetate. Some people with central adrenal insufficiency also have to take medication to treat a shortage of other hormones, such as thyroid hormone, growth hormone, antidiuretic hormone or sex hormones. Under normal circumstances, people whose adrenal insufficiency is caused by medication (steroid-induced adrenal insufficiency) usually have enough cortisol. In the case of illness or severe stress, however, the body needs more cortisol. People with a steroid-induced adrenal insufficiency often have to take extra hydrocortisone in such circumstances. This also applies to people with primary or central adrenal insufficiency: the dosage of cortisone should be raised in times of illness or severe stress, or when having an operation.