Short answer · Medically reviewed summary · Last updated: 2026-04-06
Addison disease, or primary adrenal insufficiency, is primarily caused by the immune system mistakenly attacking and destroying the outer layer of the adrenal glands, known as the adrenal cortex. Autoimmune and Pathophysiological Mechanisms In the vast majority of cases in developed nations, Addison disease is an autoimmune disorder. Think of the adrenal glands as the body’s "emergency response center," responsible for producing cortisol and aldosterone.
12 people with Addison Disease have shared their first-person experience on this question at DiseaseMaps.
Which are the causes of Addison Disease?
Causes of Addison Disease explained: genetic and environmental factors, reviewed against medical sources, plus patient perspectives.
Addison disease, or primary adrenal insufficiency, is primarily caused by the immune system mistakenly attacking and destroying the outer layer of the adrenal glands, known as the adrenal cortex.
Autoimmune and Pathophysiological Mechanisms
In the vast majority of cases in developed nations, Addison disease is an autoimmune disorder. Think of the adrenal glands as the body’s "emergency response center," responsible for producing cortisol and aldosterone. In Addison disease, the body’s defense system identifies these hormone-producing cells as foreign invaders, leading to gradual destruction. This loss of function prevents the body from maintaining blood pressure and responding effectively to physical stress.
Genetic and Environmental Factors
While the exact trigger remains a subject of ongoing research, scientists believe a combination of genetic predisposition and environmental factors is at play. Certain genetic markers within the HLA (Human Leukocyte Antigen) complex are frequently associated with an increased risk of developing Addison disease. However, carrying these genes does not guarantee one will develop the condition; an environmental "trigger"—such as a viral or bacterial infection—may be required to initiate the autoimmune response.
Secondary Causes and Etiology
Beyond autoimmunity, the condition can be caused by other mechanisms. These include infections like tuberculosis (historically a leading cause), fungal infections, or rare genetic conditions such as Adrenoleukodystrophy (ALD). In some cases, the adrenal glands are damaged by metastatic cancer or hemorrhage. It is important to distinguish between "causes," which are the direct biological events leading to gland failure, and "risk factors," which are the underlying genetic or environmental traits that make an individual more susceptible to those events.
Current Research
Medical researchers are currently utilizing genomic sequencing and longitudinal studies to better understand why the immune system loses its ability to distinguish "self" from "non-self" in patients with Addison disease. Current efforts are focused on identifying biomarkers that could predict the onset of adrenal failure before symptoms like skin darkening or dizziness become severe.
Medical Disclaimer: This information is for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your endocrinologist or other qualified health provider regarding any medical condition.
References
- National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD)
- Orphanet: The portal for rare diseases and orphan drugs
- Online Mendelian Inheritance in Man (OMIM)
- The Addison's Disease Self-Help Group (ADSHG)
Posted Mar 11, 2017 by justdeirdre 1051
Posted Mar 12, 2017 by S 2350
Posted Mar 12, 2017 by Vikki 1000
Posted Apr 27, 2017 by Missy 1650
- There are many more secondary causes; some include issues of the pituitary gland or hypothalamus, causing a breakdown in the HPA axis and thus not allowing the adrenals to be signalled into producing cortisol correctly. Others include tumours of the adnerals or pituitary.
Posted May 30, 2017 by Lucienne 800
Your adrenal glands are composed of two sections. The interior (medulla) produces adrenaline-like hormones. The outer layer (cortex) produces a group of hormones called corticosteroids, which include glucocorticoids, mineralocorticoids and male sex hormones (androgens).
Some of the hormones the cortex produces are essential for life — the glucocorticoids and the mineralocorticoids.
Glucocorticoids. These hormones, which include cortisol, influence your body's ability to convert food fuels into energy, play a role in your immune system's inflammatory response and help your body respond to stress.
Mineralocorticoids. These hormones, which include aldosterone, maintain your body's balance of sodium and potassium to keep your blood pressure normal.
Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, libido and a sense of well-being in both men and women.
Posted Sep 12, 2017 by Tina 2050
The minority can arise due to tuberculosis.
Posted Feb 16, 2019 by Edward 1400
Posted Jun 24, 2017 by Elineuda 1280
Posted Oct 18, 2017 by Susana 2000
Posted Oct 31, 2017 by Dayana 2520
Posted Nov 6, 2017 by ana carolina 1000
