Addison’s disease is a serious but rare disease. The adrenal cortex produces too little of certain vital hormones. The insidious thing is that the skin of those who are sick turns brown, which makes them look particularly healthy in the early stages of the disease. However, if left untreated, Addison’s disease is fatal. A so-called Addison crisis is particularly dangerous. Read everything you need to know about Addison’s disease below.
ICD codes for this disease: E27 E35 E23
- Symptoms: tanning of the skin, exhaustion and lethargy, low blood pressure, weight loss, dehydration.
- Course of the disease and prognosis: If treated, life expectancy is normal; if left untreated, the disease is fatal. In stressful situations, it is important to adjust hormone doses to prevent a life-threatening Addisonian crisis.
- Causes: In primary Addison’s disease, it is usually an autoimmune disease, but also various other diseases and malfunctions of the pituitary and hypothalamus.
- Diagnosis: Various laboratory tests, checking cortisone and ACTH levels, ACTH stimulation test, imaging procedures.
- Treatment: Lifelong intake of the missing hormones.
What is Addison’s disease?
Addison’s disease, also known as Hypocortisolism or Addinson’s disease, occurs when there is a lack of certain hormones (transmitters) from the adrenal cortex. Some messenger substances that are essential for survival are formed in the adrenal glands. It sits in the shape of a cap on the kidney and is divided into the adrenal medulla (NNM) and the adrenal cortex (NNR) below its protective capsule.
While the so-called catecholamines, above all adrenaline and noradrenaline, are produced in the marrow, the cortex produces androgens (sex hormones) as well as aldosterone and cortisol in two different zones.
In order to understand how the typical symptoms of Addison’s disease come about, it is important to understand the functions of the adrenal cortex hormones:
Cortisol belongs to the group of glucocorticoids. This designation contains part of the word “glucose”, i.e. sugar, which cortisol has a significant effect on: In stressful situations, the hormone stimulates metabolic processes that provide energy in the form of sugar. For this, however, proteins, which are mainly found in muscle tissue, are used up and fats are created as emergency reserves. In addition, cortisol has a significant effect on the metabolism of bones, skin, muscles and connective tissue.
Cortisol also has an effect on the digestive tract (appetite), sex drive and the psyche. In higher concentrations, the hormone has an anti-inflammatory effect by regulating the body’s immune system. Doctors take advantage of this, for example, to combat allergic symptoms or autoimmune diseases.
Aldosterone is what is known as a mineralocorticoid. If this hormone is missing, the human being is not viable. In the kidneys, aldosterone regulates fluid balance by retaining water and the important electrolyte sodium. It is therefore vital for maintaining blood pressure and regulating mineral metabolism.
Androgens are hormones that are converted in body tissues to the sex hormones testosterone or estrogen. Small amounts of the male sex hormone testosterone are also released by the adrenal cortex in women. In women, androgens cause, among other things, pubic hair to grow.
Regulatory circuit of hormones
Whether the adrenal cortex releases hormones and how much is subject to a finely regulated control mechanism in the body, in which the brain plays a central role. The overseeing organ is the hypothalamus. It sits deep in the brain and is also called the “master gland” because of its overriding function. Information from the various measuring stations in the body about blood sugar, blood pressure, temperature and much more converge in the hypothalamus.
The hypothalamus responds by sending signals to release certain hormones. In the event of a lack of cortisol, the hypothalamus releases the messenger substance CRH (Corticotropin Releasing Hormone). This causes the pituitary gland (pituitary gland) to release ACTH (adrenocorticotropic hormone). The ACTH in turn reaches the adrenal cortex via the blood, where it transmits the signal for the release of cortisol.
Types of Addison’s disease
A deficiency of the adrenal cortex hormones occurs when the adrenal gland itself is affected by a disease (primary adrenal cortical insufficiency) or when the superordinate regulatory centers in the brain are disturbed (secondary or tertiary adrenal cortical insufficiency).
What are the symptoms of Addison’s disease?
If the adrenal gland itself is affected by a disease in primary adrenal cortical insufficiency, around 90 percent of the cortex has already been destroyed by the time the typical symptoms appear. The following key symptoms are present in more than 90 percent of those affected:
Browning of the skin: The darker tint of the skin has given the disease the nickname “bronze disease”. As a result of the lack of cortisol, the pituitary gland produces more ACTH, which is supposed to boost cortisol production. This produces more melanocyte-stimulating hormone (MSH). Under its influence, the melanocytes produce more of the skin pigment melanin. The brown tint of the skin is particularly visible in the oral mucosa and skin lines. However, this symptom only occurs in primary Addison’s disease.
Low blood pressure: Due to the lack of the hormone aldosterone, which regulates the mineral and thus the water balance, the blood pressure drops to the point of circulatory failure.
Other symptoms are:
- General exhaustion and severe listlessness (adynamia).
- Weight loss and dehydration (dehydration).
Weight gain is not a typical symptom of Addison’s disease, but is a possible side effect of glucocorticoid therapy.
In addition to the typical Addison’s disease symptoms, the hormone deficiency is noticeable on other levels:
- Hunger for salty foods.
- Tiredness, exhaustion.
- Digestive problems such as nausea, vomiting or abdominal pain.
- Absence of pubic hair in women, problems with potency in men.
- Mental problems such as depression, irritability and apathy.
- Growth arrest in infants.
Depending on the duration and severity of the hypofunction of the adrenal cortex, the symptoms vary greatly from person to person. While some people have no symptoms at all under normal everyday conditions, the disease manifests in others with the full range of symptoms.
Especially with a slowly progressing primary Addison’s disease, it happens that those affected and doctors misinterpret the gradually developing symptoms and interpret them as exhaustion syndrome or signs of aging. The large number of life-threatening symptoms shows how important the hormones are, which have enormous effects even in tiny concentrations.
Symptoms of the Addison Crisis
The Addisonian crisis is a particularly severe form of Addison’s disease, which develops primarily in psychological or physical stressful situations. The hormone deficiency that occurs suddenly leads to life-threatening circulatory disorders and even coma. Typical symptoms of the Addisonian crisis are:
- Drop in blood pressure.
- Massive loss of fluid through the kidneys and imminent dehydration of the body.
- Circulatory collapse to the point of shock and circulatory failure.
- Dangerously low blood sugar (hypoglycemia).
- Severe abdominal pain.
Doctors often diagnose existing adrenal insufficiency with an Addisonian crisis for the first time. The acute life-threatening condition can only be averted with a high dose of hydrocortisone. The emergency doctor must act quickly here!
Is Addison’s disease curable?
With the exception of tertiary Addison’s disease, Addison’s disease cannot be cured, but is easily treatable. If a slowly progressing, chronic Addison’s disease is recognized in time, the disease can be well controlled by taking the vital hormones. Despite the lifelong hormone substitution, those affected have a normal life, their lifespan and quality of life are comparable to those of healthy people. As a rule, permanent impairments are not to be expected.
Problems are possible if the hormone concentration is not adjusted to a prevailing stress situation. In this case, an Addisonian crisis can occur, which is life-threatening if medical treatment is not received in time. If left untreated, Addison’s disease is always fatal.
Causes and risk factors
Causes of Addison’s disease are diseases of the adrenal gland itself, the superordinate control points in the brain, the pituitary gland or the hypothalamus. In Addison’s disease, they lead to a life-threatening hormone deficiency.
Important causes of primary adrenal insufficiency, in which the adrenal gland itself is diseased, are:
Autoimmune adrenalitis: This disease is the most common cause at around 80 percent. The body’s own cells target the adrenal gland tissue and slowly destroy it. Addison’s disease is often associated with other autoimmune diseases, such as chronic inflammation of the thyroid gland (Hashimoto’s thyroiditis).
Waterhouse-Friderichsen Syndrome: Severe blood poisoning , mainly due to meningococci, sometimes leads to an infarction of the adrenal vessels. The adrenal gland does not get enough blood and suddenly fails.
Infections: In some cases, infections with certain pathogens are responsible for the destruction of the adrenal glands. In the age of tuberculosis, this was the main cause of Addison’s disease. But histoplasmosis, AIDS or the cytomegalovirus sometimes lead to Addison’s disease.
Bleeding: In rare cases, blood-thinning drugs lead to bleeding into the adrenal glands and can severely damage them.
Tumors: Very rarely, tumors of the adrenal cortex or metastases from other tumors are responsible for their loss of function.
Heredity: Congenital adrenal hypoplasia, for example, is inherited. The underdevelopment of the adrenal glands already leads to severe symptoms in infancy.
Malfunctions of the overriding regulation in the brain, the pituitary gland or the hypothalamus also cause Addison’s disease. To this form of secondary adrenal insufficiency is very rarely caused by damage to these areas of the brain from a stroke, tumors, skull injuries or brain surgery.
Tertiary adrenal insufficiency is caused by long-term use of high-dose cortisone preparations. This suppresses the production of the hormone CRH in the hypothalamus. The downstream pituitary produces less ACTH and the adrenal cortex therefore throttles hormone production. If those affected stop taking cortisone, the adrenal cortex only slowly starts producing the hormones again, so that there is initially a deficiency. It is therefore important to always gradually taper off cortisone medication and never stop suddenly.
Investigations and diagnosis
The doctor first detects typical Addison’s disease symptoms in a detailed discussion with those affected. The specialized endocrinologist gains an initial assessment based on this information on the medical history.
He then investigates the suspicion of adrenal insufficiency with blood tests and laboratory tests. In addition to the usual blood values and blood salts (electrolytes), the focus is on the hormone levels of cortisol from the adrenal cortex and ACTH in the pituitary gland. The cortisol levels are significantly reduced in acute Addison’s disease, but in the case of a chronic course of the disease they may even be normal, especially in the morning. Therefore, an additional 24-hour follow-up of the urine is useful.
A so-called ACTH stimulation test helps the doctor to find the cause of Addison’s disease: For this purpose, the affected person receives the pituitary hormone ACTH via the vein. The doctor then determines the cortisol level in the blood. If it rises, the adrenal gland is still functional and the cause is most likely in the pituitary gland. On the other hand, if the cortisol level remains low despite ACTH administration, there is probably primary adrenal insufficiency.
An autoimmune disease can also be detected using a special antibody test. The doctor uses imaging methods such as computer or magnetic resonance imaging or ultrasound to find tumors or infarcts.
The only therapy for primary and secondary Addison’s disease is to take the missing hormones for life (replacement therapy). Those affected usually take hydrocortisol in combination with fludrocortisol two to three times a day . In women who experience a loss of libido, treatment with another hormone (dehydroepiandrosterone, DEHA) is possible.
In stressful situations, it is important to have the doctor adjust the dose so that a hormone deficiency does not occur. This also applies to situations that do not mean psychological stress for the person concerned but put a strain on the body, such as infections and operations.
Addison’s disease, with the exception of tertiary adrenal insufficiency, is incurable. Those affected need hormone therapy for the rest of their lives, since the disease is fatal if left untreated. A special diet is not required for Addison’s disease.