Addison’s disease, also known as adrenal insufficiency, is a condition in which the adrenal glands (located above each kidney) fail to secrete an adequate amount of the hormones that impact organs and tissues all over the body, resulting in a variety of symptoms, including weight loss, fatigue, mood changes, and low blood pressure. It is typically caused by a defective immune response, but infectious diseases and steroid use are other causes.
The adrenal glands are divided into two layers: the outer layer (cortex) and the inner layer (medulla). The medulla secretes hormones like epinephrine, whereas the cortex produces corticosteroids.
If there is damage to the cortex, the secretion of aldosterone, cortisol, and androgens is disrupted.
Here, we will look at the causes of Addison’s disease.
Disruption of the adrenal glands
When the adrenal cortex is damaged, hormone secretion in the adrenal glands gets disrupted, resulting in Addison’s disease.
The most common causes of Addison’s disease include:
- Faulty autoimmune response
- Genetic factors
- Adrenal or pituitary gland injury or bleeding
- Conditions like tuberculosis (TB), cancer, and HIV
- Surgical removal of the adrenal or pituitary glands
- Chronic steroid use
Types of adrenal insufficiency
- Primary adrenal insufficiency
Addison’s disease is the medical term for this condition, which is caused by an injury to the outer layer of the adrenal gland (the adrenal cortex). The adrenal insufficiency causes are:
- An autoimmune disease
- Infections such as cytomegalovirus, tuberculosis, and HIV
- Bleeding in the adrenal glands due to injury, trauma, and blood clotting
- Conditions such as congenital adrenal hyperplasia, cancer, amyloidosis, and hemochromatosis
- Use of drugs that inhibit cortisol production, such as etomidate and ketoconazole
- Secondary adrenal insufficiency
Problems with the pituitary can indirectly cause Addison’s disease. Adrenocorticotropic hormone (ACTH) is secreted by the pituitary gland and stimulates the adrenal glands to secrete other hormones. When the pituitary gland fails to produce enough ACTH, the adrenal glands fail to produce sufficient cortisol as a result. Secondary adrenal insufficiency can also be caused by:
- Surgical removal of the pituitary gland
- Pituitary infections or tumours
- Bleeding in the pituitary gland
- Genetic conditions affecting the pituitary gland
Secondary adrenal deficiency could also occur when a person takes steroid medications that impact the hypothalamus and pituitary gland, preventing the body from producing ACTH. This results in a decrease in glucocorticoid steroid levels.
The immune system protects the body from infections, diseases, and toxins. The body’s immune system attacks and harms healthy tissues and organs in people who have an autoimmune condition. The body’s immune system attacks adrenal gland cells in Addison’s disease, causing these cells to stop working eventually.
People who suffer from any of the following autoimmune conditions are highly likely to develop autoimmune Addison’s disease.
- Type 1 diabetes
- Pituitary or thyroid gland problems, including Grave’s disease
- Dermatitis herpetiformis
- Myasthenia gravis
- Pernicious anaemia
Genetic factors for addison’s disease causes
Adrenal insufficiency is more common in individuals with certain genetic characteristics and conditions, including:
- Congenital adrenal hyperplasia (a cluster of disorders affecting the production of cortisol at birth)
- Adrenal leukodystrophy
- Wolman disease (characterised by adrenal gland calcification)
- Antiphospholipid syndrome (APS)
The human leukocyte antigen (HLA) complex includes the genes most likely linked to autoimmune Addison’s disease. This genetic complex aids the immune system in distinguishing between proteins produced by the body and those synthesised by bacteria and viruses.
Bleeding in the adrenal glands
Bleeding into the adrenals, also known as adrenal haemorrhage, can result from:
- njury or blunt trauma
- Blood clotting caused by disseminated intravascular coagulation
- Tumour development
- Use of anticoagulants
Cancer can lead to Addison’s disease in different ways, such as:
- Tumours evolving in the adrenal glands can cause this condition.
- Metastasis, which occurs when cancer spreads to the adrenal glands from another area, can be responsible for this disease.
- The development of lymphoma can lead to this condition.
Researchers are also investigating whether certain cancer treatments, such as steroids combined with chemotherapeutics, may increase the likelihood of fatigue caused by adrenal insufficiency.
The following infections can increase the likelihood of Addison’s disease:
- Fungal infections, including histoplasmosis
These infections can harm the adrenal glands and impair hormone production.
Some individuals undergo adrenalectomy (a surgical procedure that removes the adrenal glands), which ultimately causes Addison’s disease.
A doctor may suggest this surgery if:
- There is cancer in the adrenal glands,
- Tumours have spread (metastasised), for example, from the kidneys to the adrenal glands,
- The glands are oversecreting hormones, for instance, in Cushing’s syndrome or in Conn’s syndrome,
- The size of the glands has changed.
Surgical removal of the pituitary gland may have an effect on hormone secretion in the adrenal glands as well.
Steroids are used to manage inflammation in various conditions. Long-term use of steroids, on the other hand, can disrupt the secretion of hormones in the adrenal glands, thereby increasing the risk of Addison’s disease.
When an individual takes glucocorticoids, which include hydrocortisone, cortisone, dexamethasone, and prednisone, the body precepts a rise in cortisol and generates less ACTH. As a consequence, the adrenal glands secrete lower levels of hormones than normal.
A sudden discontinuation of oral corticosteroids can result in adrenal insufficiency. Over the course of several weeks or months, a physician will steadily reduce the dose to restore the adrenal gland’s normal function.
Adrenal insufficiency can also arise after the effective treatment of Cushing’s syndrome. In this condition, the body produces an abnormally high level of cortisol. Treatment lowers cortisol levels but temporarily disrupts adrenal gland function.
Addison’s disease emerges because the adrenal glands stop producing hormones. The primary cause of Addison’s disease is a defective autoimmune response. Other causes involve injury, diseases including cancer, HIV, and tuberculosis, and steroid use.
Tiredness and weight loss are common symptoms of this condition, but they might appear at a later stage because the rate of progression is gradual. Over time, an Addisonian crisis may occur, in which symptoms become suddenly severe and could be fatal.