Short answer · Medically reviewed summary · Last updated: 2026-05-08
Adrenal insufficiency occurs when the adrenal glands do not produce enough essential hormones, primarily cortisol and sometimes aldosterone. The causes of Adrenal Insufficiency are categorized into primary forms, where the glands themselves are damaged, and secondary forms, where the brain fails to signal the glands to function. What causes primary Adrenal Insufficiency? Primary Adrenal Insufficiency, often referred to as Addison’s disease, occurs when the adrenal cortex is damaged.
4 people with Adrenal Insufficiency have shared their first-person experience on this question at DiseaseMaps.
Which are the causes of Adrenal Insufficiency?
Causes of Adrenal Insufficiency explained: genetic and environmental factors, reviewed against medical sources, plus patient perspectives.
Adrenal insufficiency occurs when the adrenal glands do not produce enough essential hormones, primarily cortisol and sometimes aldosterone. The causes of Adrenal Insufficiency are categorized into primary forms, where the glands themselves are damaged, and secondary forms, where the brain fails to signal the glands to function.
What causes primary Adrenal Insufficiency?
Primary Adrenal Insufficiency, often referred to as Addison’s disease, occurs when the adrenal cortex is damaged. The most common cause in developed countries is autoimmune destruction, where the body's immune system mistakenly attacks its own adrenal cells. Other causes include:
- Infections: Tuberculosis, fungal infections, or HIV/AIDS can infiltrate and destroy adrenal tissue.
- Genetic conditions: Disorders like Congenital Adrenal Hyperplasia (CAH) involve inherited enzyme deficiencies that prevent cortisol production.
- Hemorrhage or trauma: Severe bleeding into the adrenal glands, sometimes during sepsis, can cause sudden failure.
- Surgical removal: Bilateral adrenalectomy leads to absolute Adrenal Insufficiency.
What is the difference between primary and secondary Adrenal Insufficiency?
While primary Adrenal Insufficiency involves the glands themselves, secondary Adrenal Insufficiency is caused by a problem with the pituitary gland or hypothalamus. These brain structures produce adrenocorticotropic hormone (ACTH), which tells the adrenal glands to work. If the pituitary gland is damaged by a tumor, radiation, or surgery, it stops sending this signal, and the adrenal glands atrophy from lack of stimulation.
Are genetic factors involved in Adrenal Insufficiency?
Yes, genetics play a significant role in specific types of Adrenal Insufficiency. For example, Congenital Adrenal Hyperplasia is an autosomal recessive condition caused by mutations in genes such as CYP21A2. Additionally, rare conditions like X-linked adrenoleukodystrophy involve genetic mutations that result in the progressive destruction of adrenal tissue. Research is ongoing to identify polygenic markers that may predispose individuals to autoimmune Adrenal Insufficiency.
Next steps
- Consult an endocrinologist to undergo ACTH stimulation testing to confirm the diagnosis.
- Connect with the 113 members of the DiseaseMaps.org community to share experiences and coping strategies.
- Carry a medical alert identification card or bracelet at all times.
- Discuss stress-dose steroid protocols with your physician to prevent adrenal crisis.
Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment.
References
- NIH Genetic and Rare Diseases (GARD) Information Center: Adrenal Insufficiency overview.
- Orphanet: Rare diseases related to adrenal cortex hypofunction.
- OMIM (Online Mendelian Inheritance in Man): Database for genetic variants related to adrenal disorders.
- The Pituitary Foundation: Resources on secondary adrenal insufficiency.
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Posted Apr 19, 2017 by Bubbly 2101
Autoimmune disorders cause most cases of Addison’s disease. Infections and medications may also cause the disease.
Autoimmune Disorders
Up to 80 percent of Addison’s disease cases are caused by an autoimmune disorder, which is when the body’s immune system attacks the body’s own cells and organs.2 In autoimmune Addison’s, which mainly occurs in middle-aged females, the immune system gradually destroys the adrenal cortex—the outer layer of the adrenal glands.2
Primary adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed.1 As a result, both cortisol and aldosterone are often lacking. Sometimes only the adrenal glands are affected. Sometimes other endocrine glands are affected as well, as in polyendocrine deficiency syndrome.
Polyendocrine deficiency syndrome is classified into type 1 and type 2. Type 1 is inherited and occurs in children. In addition to adrenal insufficiency, these children may have
underactive parathyroid glands, which are four pea-sized glands located on or near the thyroid gland in the neck; they produce a hormone that helps maintain the correct balance of calcium in the body.
slow sexual development.
pernicious anemia, a severe type of anemia; anemia is a condition in which red blood cells are fewer than normal, which means less oxygen is carried to the body’s cells. With most types of anemia, red blood cells are smaller than normal; however, in pernicious anemia, the cells are bigger than normal.
chronic fungal infections.
chronic hepatitis, a liver disease.
Researchers think type 2, which is sometimes called Schmidt’s syndrome, is also inherited. Type 2 usually affects young adults and may include
an underactive thyroid gland, which produces hormones that regulate metabolism
slow sexual development
diabetes, in which a person has high blood glucose, also called high blood sugar or hyperglycemia
vitiligo, a loss of pigment on areas of the skin
Infections
Tuberculosis (TB), an infection that can destroy the adrenal glands, accounts for 10 to 15 percent of Addison’s disease cases in developed countries.1 When primary adrenal insufficiency was first identified by Dr. Thomas Addison in 1849, TB was the most common cause of the disease. As TB treatment improved, the incidence of Addison’s disease due to TB of the adrenal glands greatly decreased. However, recent reports show an increase in Addison’s disease from infections such as TB and cytomegalovirus. Cytomegalovirus is a common virus that does not cause symptoms in healthy people; however, it does affect babies in the womb and people who have a weakened immune system—mostly due to HIV/AIDS.2 Other bacterial infections, such as Neisseria meningitidis, which is a cause of meningitis, and fungal infections can also lead to Addison’s disease.
Other Causes
Less common causes of Addison’s disease are
cancer cells in the adrenal glands
amyloidosis, a serious, though rare, group of diseases that occurs when abnormal proteins, called amyloids, build up in the blood and are deposited in tissues and organs
surgical removal of the adrenal glands
bleeding into the adrenal glands
genetic defects including abnormal adrenal gland development, an inability of the adrenal glands to respond to ACTH, or a defect in adrenal hormone production
medication-related causes, such as from anti-fungal medications and the anesthetic etomidate, which may be used when a person undergoes an emergency intubation—the placement of a flexible, plastic tube through the mouth and into the trachea, or windpipe, to assist with breathing
What causes secondary adrenal insufficiency?
A lack of CRH or ACTH causes secondary adrenal insufficiency. The lack of these hormones in the body can be traced to several possible sources
Posted Jan 9, 2018 by Linda 1520
Posted Jan 29, 2024 by AdrienneSmith 1600
