The Truth About Adrenal Fatigue

The term “adrenal fatigue” has gained popularity over the last two decades to explain symptoms that are seen in those who have been dealing with long-term physical or emotional stress1. The term originated from Dr. James Wilson, a chiropractor and naturopath and was used to explain the generalized symptoms, a few being that of fatigue, weight gain, trouble sleeping, caffeine dependence, or salt cravings, in this chronically stressed population1,2. Dr. Rashmi Mullur, an endocrinologist notes in her paper Making a Difference in Adrenal Fatigue that there are several issues with the current theory2. The reason why this idea has not gained any footing in the realm of traditional medicine and why it has not been endorsed by the Association of American Medical College or the American Board of Medical Specialties is due to the physiologic misrepresentation of the hypothalamic-pituitary-adrenal (HPA) axis2,3.

The hypothalamus releases corticotropin releasing hormone (CRH), which is a signal that causes the release of adenocorticotropic hormone (ACTH) from the pituitary that in turn signals the adrenal glands to release cortisol. That release of cortisol can then signal to the hypothalamus and pituitary indicating that there is enough cortisol produced, which is called negative feedback.

The theory behind adrenal fatigue is that due to a chronic exposure to stress the adrenal glands burn out, so to speak, and cannot produce enough cortisol to meet the body’s demand3. There is no data supporting that this is true. Extensive research has shown that the body does increase cortisol in the body when exposed to stress, but there is no evidence supporting that it ever reaches a point of not being able to sustain. Here are some of the underlying conditions and how they are categorizes that do affect the adrenal gland leading to adrenal insufficiency:

Primary adrenal insufficiency – at the level of the adrenal gland

  • Addison’s disease, the autoimmune destruction of adrenal cortical tissue

  • Adrenal hemorrhage that is associated with sepsis

  • Adrenal infiltrates such as tumors, amyloidosis, hemochromatosis

Secondary adrenal insufficiency – at the level of the pituitary

  • Related to a decrease in adrenocorticoptropic hormone (ACTH) from the pituitary from pituitary tumors or tumors of surrounding structures in the brain, pituitary infarct (decreased blood flow leading to ischemic damage), or congenital anomalies.

Tertiary adrenal insufficiency – at the level of the hypothalamus

  • Generally related to long-term exogenous corticosteroid use, which caused chronic suppression (negative feedback) of corticotropin releasing hormone (CRH) from the hypothalamus

In 2016, a comprehensive, systematic search was conducted by BMC Endocrine Disorders to assess whether any previously published literature supported the ideals surrounding adrenal fatigue. The study concluded that no current data exists to support the claim that adrenal fatigue is an actual pathophysiologic condition3. Some of the symptoms that are used to describe adrenal fatigue are also confusing, given that they represent symptoms of both adrenal insufficiency (fatigue, salt disturbances) and Cushing’s syndrome (weight gain, trouble sleeping), which is a syndrome related to elevated cortisol levels.

However, the symptoms that these patients are experiencing should not be ignored. Though the data does not support that there is anything wrong with the adrenal gland in these patients, there is data supporting that there may be some other changes that may be responsible for what these patients are experiencing. Research done in neurology and psychiatry looked into changes in cortisol pathways in those with diagnosed post-traumatic stress disorder (PTSD). This research noted that there were changes in 24 hour cortisol patterns as well as elevation in CRH in the brain2, 4-5. What these studies also indicated was that there was a change in the architecture of an area of the brain known as the limbic system, which includes the hypothalamus, that is responsible for steady state regulation of the body (homeostasis), emotions and drives, as well as memory and olfaction (sense of smell)4-5. So it makes sense that what these people are experiencing in terms of sleep disturbances, weight changes, fatigue, etc. can be attributed to what this research has demonstrated.

This, however, Dr. Mullur notes, is not to say that these issues should be dismissed as being all in their head, but should be approached with knowledge on part of the provider to explain what could actually be going on and then to offer tools to help patients manage their stress. Dr. Mullur, who is actually a double-boarded specialist in endocrinology and integrative medicine, mentions in her paper that there is evidence supporting the use of meditation, yoga, and tai chi in changing the architecture of the brain in those who experience trauma, improving their quality of life as well as helping them manage their stress2.


  1. Hormone Health Network. Myth vs Fact: Adrenal Fatigue. 2019.

  2. Rashmi S. Mullur (2018) Making a Difference in Adrenal Fatigue. Endocrine Practice: December 2018, Vol. 24, No. 12, pp. 1103-1105.

  3. Cadegiani F, Kater C. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. 2016 Aug 24;16(1):48. doi: 10.1186/s12902-016-0128-4.

  4. Yehuda R. Post-traumatic stress disorder. N Engl J Mod. 2002;346:108-114.

  5. Henckens MJDeussing JMChen A.Region-specific roles of the corticotropin-releasing factor-urocortin system in stress.Nat Rev Neurosci. 2016 Oct;17(10):636-51. doi: 10.1038/nrn.2016.94.