Addison disease, the traditional term for primary adrenal insufficiency, is an uncommon disorder that occurs when your body does not produce enough of certain hormones.
In Addison disease, the adrenal glands (located just above the kidneys) do not make enough steroid hormones (cortisol and aldosterone) due to the destruction or dysfunction of the entire adrenal cortex, which ends in steroid hormones deficiency.
In 1855 it was discovered for the first time by Dr. Thomas Addison, from the University of Edinburgh School of Medicine; he uncovers it in his article called On the Constitutional and Local Effects of Adrenal Gland Disease.
In the United States, Addison’s disease’s frequency is 40 to 60 cases per million population. It occurs in men and women alike and all age groups but is most common in the 30 to 50 age range. The principal treatment for people with Addison’s disease consists of supplying hormones to replenish the ones lost due to damage or the adrenal gland’s destruction.
By reading this article, you will learn leading information about Addison’s disease, including its causes, symptoms, and possible complications, directly from a doctor.
What are the adrenal glands?
The adrenal glands are two small triangular-shaped glands with their location in the upper part of the kidneys. They are responsible for producing hormones essential for the human body’s functioning.
The adrenal glands are composite of two parts. The interior (medulla) produces hormones such as adrenaline. The outer layer (cortex) is partite into three zones.
So, the zona glomerulosa produces aldosterone, and the zona fasciculata and reticularis together produce cortisol and adrenal androgens.
How adrenal glands work?
The adrenal glands are essential in hormonal regulation. The hypothalamus-hypophysis-adrenal axis begins in the hypothalamus, which produces corticotropin-releasing hormone (CRH).
This latter hormone activates the pituitary (a small organ located at the base of the brain) to produce adrenocorticotropic hormone (ACTH), which, in turn, stimulates the adrenals glands to produce corticosteroids or steroid hormones.
What is the function of cortisol and aldosterone?
Cortisol, a hormone of great importance in the body due to its multiple functions, belongs to the glucocorticoid family. It is the main responsible for responding to a stressful stimulus for the body. It is also responsible for controlling both blood pressure and glucose levels in the blood, decreasing the immune system’s response, and aid metabolism.
Aldosterone belongs to the group of mineralocorticoids; its functions include stabilizing sodium and potassium in the blood and maintaining blood pressure.
What are adrenal insufficiency and Addison’s disease?
Adrenal insufficiency also called primary adrenal insufficiency is a hormonal alteration. The adrenal gland cannot produce enough cortisol and aldosterone, creating an imbalance causing diseases such as Addison’s disease.
Adrenal insufficiency is classified mainly as primary when the adrenal gland does not function properly and, therefore, cannot produce hormones. Here, the problem is from the gland itself.
On the other hand, when the adrenal glands have no damage or impairment but cannot produce these hormones for other reasons, there is a secondary adrenal insufficiency, which also receives the name of central adrenal insufficiency.
This type is mainly due to the absence of the corticotropin-releasing hormone (CRH) from the hypothalamus or adrenocorticotropic hormone (ACTH) at the pituitary level, decreasing the production of steroid hormones.
What are the causes of Addison’s disease?
Around eighty percent of Addison’s disease or primary adrenal insufficiency cases is because of the progressive destruction of the cortex of the adrenal gland; the name for it is idiopathic autoimmune adrenocortical insufficiency.
The body’s immune system is recognizing the gland as foreign, attacking, and producing its disruption, leading to adrenal insufficiency when at least 90% of the cortex is found damaged. As a result, often both of them cortisol and aldosterone are lacking.
Secondly, we have infectious causes such as tuberculosis, human immunodeficiency virus, HIV / AIDS, and fungal infections.
Other causes of Addison disease include:
- Injury to the adrenal glands.
- Cancer cells that invade the adrenal glands.
- Bleeding in the adrenal glands.
- Surgical removal of the adrenal glands.
- Amyloidosis (abnormal accumulation of sure proteins in the organs)
- Genetic and harmful disorders in the growth or activity of the adrenal glands
Causes for secondary adrenal insufficiency.
Among the causes of secondary adrenal failure, we can find the non-iatrogenic and iatrogenic causes. The term “iatrogenic” refers to symptoms or illnesses because of comments or treatments by doctors.
In light of this, steroids are useful medicine for treating common conditions like autoimmune diseases. So, in the case of iatrogenic-causes, a typical cause of secondary adrenal failure is receiving treatment with steroids for other diseases (more than two weeks is enough to be at risk). Treatment with steroids can suppress the hypothalamic-pituitary axis. They produce negative feedback in upper structures like the hypothalamus or pituitary. Hence, they decrease the upper hormones that stimulate the adrenal glands, such as CRH and ACTH.
One of the most important causes of non-iatrogenic or disease-induced secondary adrenal insufficiency is a tumor in the pituitary gland. Its name is a pituitary tumor. Although there are several other causes for it.
What is the most common cause of Addison disease?
The leading cause of Addison’s disease is an idiopathic autoimmune adrenocortical insufficiency. The human body’s immune system is in charge of protecting the body against any infection by producing antibodies (a special kind of protein) that develops a protective response against any foreign agent to the body.
For unknown causes in Addison’s disease, the immune system recognizes the cortex of the adrenal gland as foreign, which leads to its destruction, interfering with the steroid hormones cortisol and aldosterone production. Hence, this is an autoimmune disorder, where the body attacks its own organs.
What causes Addison’s disease in a child?
In developed countries, the most common cause of Addison’s disease is due to the autoimmune destruction of the adrenal cortex. This is the same situation for adults. It occurs in two ways; alone or with other disorders, as in the context of a polyglandular autoimmune disorder (PGAD).
There is PGAD type 1 that tends to appear in children below ten years old. It is a genetic disorder that mainly correlates with two other conditions as mucocutaneous candidiasis and hypoparathyroidism, although with many other illnesses too, like type 1 diabetes mellitus or hypothyroidism, for example.
PGAD type 2 in patients will present as an adrenal failure plus autoimmune thyroid disease and type 1 diabetes mellitus, specifically. This condition tends to manifest later in life, like in the twenties. However, children could exhibit some features of this disease in the early days.
Another cause is congenital due to an increase or decrease in the number of adrenal gland cells that impairs the hormone production in the gland. These are known as congenital adrenal hyperplasia (when they get large in size) or hypoplasia (when they diminish in size).
Notably, all the other causes of Addison disease in the adult can similarly exist in children patients as infections, bleeding, or drugs.
However, the main cause of adrenal insufficiency in children is iatrogenic and secondary in nature with the lengthy administration of glucocorticoids. As we said, as little as two weeks of glucocorticoid treatment can suppress the adrenal axis diminishing the CRH and ACTH levels. So, similarly, this will end in an adrenal gland malfunction.
Which children are at risk for Addison disease?
Factors that make children are at risk to get Addison’s disease or adrenal insufficiency include:
- Children that have any of the following autoimmune diseases:
- Myasthenia gravis
- Family members with Addison’s disease of autoimmune origin
- Long-term steroid drug treatment (secondary adrenal insufficiency)
- Hereditary disorders, such as Prader-Willi syndrome and congenital adrenal hyperplasia
What are the symptoms?
This condition has a wide range of symptoms related to hormone deficiency in the body. The predominant symptoms depend on the time that the person has with the condition.
There are two types of presentations of Addison’s disease, chronic and acute Addisonian crisis that can be precipitated by different factors like infection, diarrhea, surgery, trauma, and others.
About the chronic condition, the symptoms can be mild and non-specific. Usually, the first medical sign is the darkening of the skin and mucous membranes as the gums; this sign can appear months or years before the other symptoms.
Other unspecific indicators can be fatigue, drop appetite, weakness, and weight loss. Gastrointestinal symptoms include vomiting, nausea, and sometimes diarrhea.
They can also suffer from muscle and joint pain and have postural hypotension, which is the low blood pressure when the person stands up from sitting or lying down. The latter could prompt symptoms like blurry vision or dizziness.
People with controlled diabetes can present sudden low blood sugar due to an unexpected increase in the insulin hormone’s responsiveness. This can result in people fainting because of these low blood sugar levels.
Addisonian crisis symptoms
When patients remain for long periods without sufficient steroid hormones, they are at risk of having a sudden shallow level of such hormones, which is an acute adrenal insufficiency, and it is a life-threatening situation.
Keep in mind that steroid hormones are necessary for several essential human body functions. So, when the body is subjected to a novel source of stress, such as infections, undergoing surgery, or severe diarrhea. Those situations could raise the body’s needs for steroid hormones, which will not appear because of the glands’ impairment. Then, acute adrenal insufficiency begins.
The acute form of the disease comes with a group of sudden symptoms like nausea, vomiting, and really low blood pressure. The person deteriorates abruptly and can also have a light blue color in the mouth or skin, severe abdominal pain, high temperatures as 104°F, and suffer from confusion and dizziness; they can even get into a coma. This is a true medical emergency that requires immediate treatment.
What organs are affected by Addison’s disease?
We already saw all the consequences that Addison disease can have on our bodies. Still, all these symptoms exist because of the impairment of one only element, the adrenal gland.
As we initially saw, this gland controls the release of a series of hormones in our body, including cortisol, aldosterone, hydrocortisone, adrenocorticotropic hormone, and others.
All these hormones play essential roles in regulating multiple metabolic pathways and core functions of the human body. Therefore, the lack of those will virtually affect and cause symptoms in the whole body.
These hormones’ insufficiency leads to other organs’ symptoms, such as heart and blood vessels, gastrointestinal system, skin, and mucous membranes, brain, etc.
What are the long-term effects of Addison’s disease?
Long-term effects of Addison disease are akin to the level of hormone deficiency that the person has. When chronic disease develops without medical treatment, it can lead to erectile dysfunction and low libido in males. In females, it can lead to dysfunctional ovaries that show as amenorrhea. This latter condition happens when females don’t have menstruation bleeding for more than one menstrual cycle.
As we saw, there are symptoms related to low blood pressure as fatigue, dizziness, and faints that can occur more often. Other consequences are related to body insecurity due to the dark skin marks that the disease causes.
When Addison’s disease is inadequately treated, an adrenal crisis can be superimposed; in this case, medical care should request the soon as possible. If not treated promptly, it could result in death. To see about the adrenal crisis, go to the symptoms section.
At what age is Addison’s disease diagnosed?
Addison disease is a rare condition; globally, there are just 40 to 60 cases per 1 million people. Normally it appears at ages between 30 and 50 years, which means that it is typically diagnosed in adults.
Moreover, when Addison’s disease is because of Idiopathic autoimmune Addison disease, it can similarly affect children. This condition can also appear early in life when associated with other conditions in the context of genetic diseases.
What tests confirm Addison’s disease?
- Electrolytes levels: a person with primary Addison disease normally present low sodium blood levels, that can be associated with high potassium blood levels.
People that suffer from the second type can also present low sodium blood levels but is less common.
- Hormone levels: we can confirm primary adrenal insufficiency if the blood cortisol levels are really low, having at the same time high ACTH blood levels and a high plasma renin activity.
When doctors find low cortisol blood levels with normal ACTH blood levels, it should think of secondary or central adrenal insufficiency.
- Rapid ACTH stimulation test: A small quantity of ACTH is injected into the body of the person; in a healthy person, the blood levels of hormones cortisol and aldosterone should increase above their regular blood levels.
In a person with primary Addison disease, its blood levels of cortisol and aldosterone will have a minimum or a zero change after 30 or 60 minutes from the ACTH injection.
- Adrenal Autoantibodies test: people with autoimmune Addison Disease have in their bodies some proteins called autoantibodies. Those proteins misbehave, attacking the person’s adrenal glands, specifically the 21-hydroxylase enzyme located there. With this test, doctors can determine if these autoantibodies are present or not in the person. It is useful for doctors when looking for an autoimmune disease, which is the cause of this disease eighty percent of the time.
Imaging studies can give us a better perspective of the Addison disease cause. An abdominal computed tomography can show an enlargement of both adrenal glands when it is related to infections or show a decreased size if an idiopathic autoimmune Addison disease.
Secondary adrenal insufficiency
Now, regarding secondary adrenal insufficiency. More specific and different tests should be done to diagnose the main cause due to the wide possibilities of causes.
One of the most causes is pituitary tumors. Their diagnosis and of the many other diseases causing this condition could be through resonance imaging (MRI) and computed tomography (CT) of the head.
What is the treatment?
Fundamentally the treatment consists of replacing the hormones that the body is not producing.
Glucocorticoid replacement is required in all forms of adrenal insufficiency. Still, mineralocorticoid replacement is only needed in primal Addison disease type.
Some of the medicines that doctors use are:
- Fludrocortisone: It replaces the body’s mineralocorticoids.
- Prednisone: It replaces body glucocorticoids.
- Hydrocortisone: It acts as a mineralocorticoid and glucocorticoid.
Patients in replacement therapy with corticosteroids need to be closely monitored by a doctor and an endocrinologist.
Treatment of secondary Addison Disease requires prior identification of the ailment, causing it; the treatment of this type is different and specific depending on the underlying cause.
When talking about an Addisonian crisis, the patient needs to be taken to an emergency room and treated by health care professionals.
Do you have symptoms and risk factors for this disease?
This tool is an Addison Disease Symptoms Checker. It gathers the most important signs, symptoms, and risk factors for this disease. Therefore, the tool will help anyone who uses it to determine their symptoms because of Addison’s disease. Also, this cool could yield a positive result if you have several risk factors for it. To use the tool is free and would only take a few minutes.