Understanding Addison's Disease: Causes, Diagnosis, and Daily Life

A guide to the biology behind Addison’s disease (Primary Adrenal Insufficiency), diagnosis, therapies to manage it, and the communities working to raise awareness.

Authors: Keon Deng, Feliscia Hill, Ash Su

August 4, 2026 at 11:00 AM

Addison’s disease is more commonly recognized as an autoimmune disease involving the adrenal cortex glands. There are famous figures diagnosed with Addison’s disease, including John F. Kennedy, who kept it a secret and relied on cortisol replacement treatment, singer Helen Reddy, who continued her career while advocating for Addison’s, and actress Kathy Burke and Olympic athlete Nathan Gafuik, who have fought through it (1).

Addison’s disease, also called Primary Adrenal Insufficiency (PAI), is a rare condition in which the adrenal glands cannot produce sufficient hormones, such as cortisol and aldosterone, which are responsible for regulating metabolism, blood pressure, the immune system, and the stress response. Addison’s is a health disorder that is prone to delays and misdiagnosis. Current known symptoms of Addison’s include fatigue, muscle weakness, hyperpigmentation, and disturbances with body chemical balance (2).

Addison’s results from the adrenal cortex being unable to produce the required amounts of glucocorticoids and mineralocorticoids (2). These are essential hormones involved in regulating proper sodium levels in the body and in stress responses (3). When this occurs, many patients experience common disease symptoms, such as fatigue, nausea, dizziness, and weight loss, but there are additional signs characteristic of Addison’s, including cravings for salt and hyperpigmentation, which form dark patches on the skin (2).

The adrenal cortex’s function may be disrupted due to a few different causes, but the most common is an autoimmune response, where the person’s own immune system attacks steroidogenic enzymes in the adrenal cortex (4). This response was found in approximately 85% of patients who have Addison’s. Addison’s is a progressive disorder, and it continues to degrade the adrenal cortex over time. While Addison’s has identified genetic components, only about 2% of those who have family members with Addison’s will develop it (4).

Three identified gene variants associated with Addison’s include MHC, CTLA4, and PTPN22, as well as other proteins that program immune responses (4). However, investigation of the genetics behind Addison’s is complex, as a patient with identified Addison’s genotypes cannot always predict their symptoms, nor does having symptoms of the disorder necessarily mean having the Addison’s genotype (4).

Addison’s is the chronic condition underlying reduced adrenal cortex function, but an acute medical emergency can occur as a result of loss of adrenal function, known as an adrenal crisis. This is a fatal condition that results in the necessity of rapid medical treatment (5). It may be caused by stopping corticosteroid medication, physical stress (infection, trauma, surgery), or a rapid progression of Addison’s or other affected brain areas (6).

Addison’s is not easy to immediately diagnose because of its slow onset, nonspecific, and potential psychiatric symptoms, such as fatigue or negative changes in mood (7, 8). About 50% of patients experience at least one case of adrenal crisis before diagnosis (9). Determining cortisol insufficiency is critical for a diagnosis of Addison’s. There are multiple tests that identify increased cortisol production in the adrenal glands, including measuring cortisol or adrenocorticotropic hormone (ACTH) levels.

While autoimmune destruction of the adrenal cortex is the most prevalent cause of Addison’s, there are also other causes including medications, hemorrhages, and other diseases or cancers. There are also other types of adrenal insufficiency. Secondary Adrenal Insufficiency results from a lack of ACTH from the pituitary gland, which causes a decrease in cortisol. Tertiary Adrenal Insufficiency is the lack of corticotropin-releasing hormone (CRH) from the hypothalamus that leads to a decrease in ACTH. While all of these types of Adrenal Insufficiencies result in decreased cortisol, they are affected at different points in the cortisol production pathway.

ACTH stimulation tests, done by injecting ACTH into the body, can be used to distinguish PAI from secondary adrenal insufficiency. If cortisol levels do not increase following the ACTH administration, it indicates the adrenal glands are not properly functioning, confirming Addison’s.

Meanwhile, CRH stimulation tests, where CRH is administered, are used to rule out other causes of adrenal insufficiency. There are also insulin tolerance tests, in which an injection of insulin triggers hypoglycemia, prompting the body to release ACTH in response to lower glucose levels. They can rule out or, if cortisol levels are too low after the test, diagnose secondary adrenal insufficiency. Imaging can also be ordered to check the adrenal or pituitary glands for abnormalities. Atrophied adrenal glands, for example, are indicative of autoimmune causes of Addison’s, while bilateral enlargement indicates infectious disease such as tuberculosis as a source.

Currently, the primary treatment for Addison’s is hormone replacement therapy that uses hydrocortisone as a replacement for glucocorticoids and fludrocortisone as a replacement for mineralocorticoids (2). Addison’s was previously fatal, but cortisol precursors first developed in the 1940s led to increased survivability of Addison’s (4). Addison’s requires long-term oral maintenance doses of hydrocortisone to resupply the adrenal cortex’s cortisol and aldosterone (4). However, for an adrenal crisis, there is an immediate need for intravenous hydrocortisone, fluid rebalance, and further preventative strategies (5). The overall root cause is the same, but the speed of this replacement is needed more urgently in an adrenal crisis.

The prevalence of Addison’s is 40-110 per million people in Western countries. Oftentimes, diagnosis of Addison’s is delayed because of overlapping symptoms with other diseases (10). The majority of recent studies have shown that Addison’s is most susceptible to ages between 30 and 50. Sources of sex rate prevalence vary, with some stating approximately equal rates for men and women (11,12), while other sources with a broader survey sample state the disease affects women more commonly (13). Surveys that observe Addison’s to be more commonly affecting women than men relate to the fact that women are more susceptible to autoimmune diseases (14,15).

Addison’s can present with psychiatric symptoms, such as depressive mood and cognitive impairment (16). However, there is increasing acknowledgment and destigmatization of symptoms of Addison’s, such as depression, which may increase the opportunities for resources in dealing with symptoms.

Addison’s is one of many invisible disabilities in which the symptoms are not physically apparent. This means that people impacted by it may face increased barriers to accessing accommodations and aid. Addison’s qualifies as an impairment under US law that enables one to receive disability benefits (17), but the process of obtaining aid can be difficult due to convoluted paperwork requirements and long processing times (18, 19). Those with less visible disabilities are subject to social scrutiny and stigma (20), including accusations of faking one’s condition for benefit (21), which heightens the importance of self-advocacy for individuals struggling with the disorder.

As incidences of autoimmune diseases in the U.S. continue to increase, there is a need for increased awareness of autoimmune diseases like Addison’s (22). Expanding research efforts can improve diagnosis accuracy, which reduces the risk of developing other complications when it comes to untreated Addison’s, such as an Adrenal Crisis (23).

Active organizations supporting Addison’s include the National Adrenal Diseases Foundation and AIU in the U.S., as well as others such as ADSHG originating in the U.K. These organizations focus on educating, supporting, and informing affected individuals, families, and the general community about diseases of the adrenal glands. The websites provide resources for patients, including support groups and fundraisers. Readers can visit these websites to research further, advocate, and spread awareness, decreasing stigma surrounding invisible diseases such as Addison’s.

References

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