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Written by Stefan Ianev

Adrenal fatigue is a common buzzword, but is it real? The term “adrenal fatigue” has been used by some doctors, healthcare providers, and the general media to describe a so-called condition caused by chronic exposure to stress.  

In fact, if you search ‘adrenal fatigue’ on Google, about 13,500,000 search results show up.  

According to this theory, chronic stress results in “overuse” of the adrenal glands and eventually leads to depletion of adrenal hormones and impaired adrenal function.  

Despite this, adrenal fatigue has not been recognized by the medical community or any Endocrinology society, who claim there is no hard evidence for its existence.  

What Is Adrenal Insufficiency? 

Adrenal insufficiency is a rare disorder characterized by inadequate production or absence of adrenal hormones.  Adrenal insufficiency may be classified as primary, which refers to the malfunction of the adrenal gland itself, as in Addison disease, or secondary/tertiary, which is due to lack of adrenal stimulation by the pituitary or hypothalamus.  

Primary adrenal insufficiency only affects 11 of 100,000 individuals [1]. Clinical symptoms are mainly nonspecific and include: 

  • fatigue 
  • weight loss 
  • hypotension (low blood pressure).  

Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation [1]. 

Is Adrenal Fatigue a Myth? 

However, unlike adrenal insufficiency, there is currently no reliable clinical diagnosis for adrenal fatigue.  A recent systematic review reported that that there is no substantiation that “adrenal fatigue” is an actual medical condition, and that adrenal fatigue is still a myth [2].  

Despite the lack of evidence to substantiate that adrenal fatigue actually exists, many people report symptoms of adrenal fatigue similar to those of adrenal insufficiency.   

Proponents of adrenal fatigue often argue that currently available tests for adrenal fatigue are not sensitive enough to detect changes in adrenal hormones. Testing for adrenal fatigue typically involves “Direct Awakening Cortisol”, “Cortisol Awakening Response”, and “Salivary Cortisol Rhythm” [2].  

However, we contend that it’s not that the tests for adrenal fatigue are not sensitive enough, but that they are largely irrelevant because the wrong mechanism has been proposed as the cause of adrenal fatigue.  

It is highly possible for cortisol and other adrenal hormones such as noradrenaline to be normal or elevated and for a person to still experience symptoms of adrenal hypofunction.

Let us explain...

The effects of the adrenal hormones are primarily mediated by the catecholamines adrenaline and noradrenaline. Adrenaline and noradrenaline are both excitatory neurotransmitters and hormones involved in the fight or flight response.  

Adrenaline has slightly more of an effect on the heart, while noradrenaline has more of an effect on the blood vessels. Noradrenaline is continuously being released into circulation at low levels while adrenaline is only released during highly stressful situations.   

Both adrenaline and noradrenaline bind to beta 2-adrenergic receptors in skeletal muscle and adipose tissue where they increase energy expenditure and lipolysis. They also bind to beta 1-adrenergic receptors expressed in cardiac and vascular tissue where they increase heart rate and blood pressure. 

Chronic sympathetic nervous system activation has been shown to reduce responsiveness of beta-adrenergic receptors due to receptor desensitization [3].  

Therefore, even if circulating levels of adrenal hormones are normal or elevated, if the activity at beta-adrenergic receptors is reduced, that will still result in adrenal hypofunction and all the associated symptoms.    

This is the same reason type II diabetics have elevated blood sugar levels despite having high insulin levels. Because the cells are not responding to the effects of insulin as a result of insulin resistance. In other words, insulin hypofunction occurs despite high insulin levels, which is exactly what occurs in adrenal fatigue.  

Therefore, it is not so much that adrenal fatigue and the associated symptoms do not exist, but more so the diagnostic criterion is incorrect. Studies have reported that beta-adrenergic receptor desensitisation occurs in both prolonged endurance and high intensity resistance training exercise, as well from ingesting stimulants like caffeine [4-6]. 

Typically, anything that produces a stress response and increases SNS activation, has the potential to desensitize the beta-adrenergic receptors. Overtime this can lead to a reduced response of the beta-adrenergic receptors and manifest as symptoms of adrenal fatigue.   


  1. Pulzer A, Burger-Stritt S, Hahner S. Morbus Addison : Primäre Nebenniereninsuffizienz [Addison’s disease : Primary adrenal insufficiency]. Internist (Berl). 2016 May;57(5):457-69. German. doi: 10.1007/s00108-016-0054-6. PMID: 27129928. 
  1. Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review [published correction appears in BMC Endocr Disord. 2016 Nov 16;16(1):63]. BMC Endocr Disord. 2016;16(1):48. Published 2016 Aug 24. doi:10.1186/s12902-016-0128-4 
  1. Seals DR, Bell C. Chronic sympathetic activation: consequence and cause of age-associated obesity? Diabetes. 2004 Feb;53(2):276-84. doi: 10.2337/diabetes.53.2.276. PMID: 14747276. 
  1. Schaller K, Mechau D, Scharmann HG, Weiss M, Baum M, Liesen H. Increased training load and the β-adrenergic-receptor system on human lymphocytes. J Appl Physiol (1985). 1999 Jul;87(1):317-24. 
  1. Fry AC, Schilling BK, Weiss LW, Chiu LZF. β2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining. Journal of Applied Physiology. 2006; 101:6, 1664-1672 
  1. Shi D, Nikodijević O, Jacobson KA, Daly JW. Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cell Mol Neurobiol. 1993;13(3):247–261. doi:10.1007/bf00733753 

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