Does the term ‘subclinical adrenal insufficiency’ or ‘adrenal fatigue’ exist?

If it does, is it possible that some of your patients have it?

The term subclinical adrenal insufficiency, leading to subclinical hypocortisolism (low cortisol production), is also referred to by some as ‘adrenal fatigue.’

In this short email, I wanted to share with you a few of the symptoms of this so-called condition and studies on sub-clinical adrenal insufficiency to help you identify if this condition is real and if so, how to find out if the next patient in front of you might be struggling from this condition.

Our adrenals secrete cortisol, also called the ‘stress hormone,’ as a response to physical, emotional, or psychological stress.

Cortisol, a powerful anti-inflammatory substance, is vital in the regulation of blood sugar levels, blood pressure, energy levels, and for healthy function. 

We have found that many patients who complained about chronic conditions, such as joint pain, fatigue, anxiety, or insomnia, had lower adrenal function or lower cortisol levels. 

Unfortunately, the majority of these patients received a prescription for the symptoms they reported and come to see us with the same complaints they initially had (or worse). 

Patients who have been through stressful events, such as emotional stress or physical trauma might be more susceptible to adrenal insufficiency. Furthermore, chronic or excessive secretion of cortisol may result in a down-regulation or resistance of glucocorticoid receptors. [Curr Opin Pharmacol. 2002 Dec; 2(6):723-9] Eventually, it might lead to sub-clinical adrenal exhaustion.  

When should you suspect sub-clinical cortisol or adrenal insufficiency?

  • You have chronic inflammation and pain. Studies found that patients with higher levels of inflammatory markers, Tumor Necrosis Factor (TNF-a) and interleukin 6 (IL-6) had lower levels of cortisol in the morning than healthy patients, a possible result of a sub-clinical adrenal insufficiency. Furthermore, patients with fibromyalgia and lower back pain were found to have lower levels of cortisol [Psychoneuroendocrinology, 37(7), 1009-1018; J Rheumatol. 1998 Jul;25(7):1374-81] 
  • You have ‘unexplained’ fatigue in the morning, afternoon, or all day. The adrenals secrete cortisol, which leads to gluconeogenesis in the liver and an increase in sugar levels. This helps us to stay alert and awake. Patients with chronic fatigue had significantly lower levels of cortisol in the evening, as well as lower levels of cortisol over 24 hours when compared to normal and healthy people. [The Journal Of Clinical Endocrinology And Metabolism, 73(6), 1224-1234] When cortisol levels reduce, they might lead to fatigue in the morning, afternoon, or during the whole day. With many patients, these levels will be sub-clinically low, meaning that they will be lower than optimal levels, but not enough to be considered as disease of the adrenals.
  • You have insomnia or sleep issues. If you wake up at night or find it difficult to fall asleep, it is possible that your adrenal is ‘pumping’ cortisol or adrenaline at night time, keeping you awake or waking you up. Studies show that exposure to light and stress are two factors that lead to the secretion of cortisol, which elevates levels of serum glucose. Elevation of cortisol reduces levels of melatonin (the sleep hormone), which might to a disturbance in sleep. This is very common with patients who find it hard to sleep, feel like they cannot relax, or wake up and describe that they are ‘awake.’
  • You experience depression or anxiety. Our adrenals are also called the ‘stress glands for a reason.’ Studies show that in adults, abnormal levels of cortisol are associated with depression, while in children elevated levels of cortisol are associated with a sensation of anxiety. [International Journal Of Geriatric Psychiatry, 28(10), 991-997; European Journal Of Dentistry, 11(2), 192-195] 

Clinical note: We found the ability of some patients to deal with any type of stress, physical or emotional, might be dependent on the function of their adrenals.

  • You have a higher tendency for consumption of alcohol or addictions. Studies indicate that the risk for dependence and for relapse after quitting, in alcohol or nicotine addicts, may be associated with deficient cortisol. [Alcohol Clin Exp Res. 2005 Apr; 29(4):517-27; International journal of psychophysiology. 2006. 59(3), 195–202]

How do I test sub-clinical cortisol or adrenal insufficiency?

In contrary to common testing of cortisol levels once a day in the morning, cortisol should be measured at least four times a day. 

Since cortisol levels fluctuate during the day, we recommend measuring cortisol levels 30 minutes after waking up, before lunch, after dinner, and before sleep. This can be done by measuring levels of cortisol in patients’ saliva.

The advantage of this test is that the collection is simple and the kit can be picked up by FedEx from the patient’s home. 

Another marker that might indicate cortisol insufficiency and an adrenal issue is Dehydroepiandrosterone sulfate (DHEAS).

In general, we have found that DHEA-S levels could provide a beneficial marker in establishing the level of insufficiency or the need for supplementation with DHEA or DHEA-S.

It is important to mention that according to the journal of the American Association of Clinical Endocrinologists, serum levels of DHEA-S are low in patients with primary or central adrenal insufficiency, however, a diagnosis of adrenal insufficiency should not be established by this marker alone.
[Endocr Pract. 2011 Mar-Apr;17(2):261-70]

How do I guide my patients with sub-clinical adrenal or cortisol insufficiency? 

The best approach to addressing sub-clinical low cortisol production is comprehensive and includes lifestyle changes and nutritional supplements and adaptogenic herbs to support adrenal function, such as Ashwagandha or Ginseng. 

Also, stress management is key in treating this condition since chronic stress leads to reactivation of the adrenals through the hypothalamic-pituitary-adrenal axis and might aggravate the exhaustion. 

A study that examined the effect of stress on cortisol found that nurses had almost double the amount of cortisol during a stressful day at work (638.1 ng/mL) in comparison to a day off (354.1 ng/mL
). [Revista Da Escola De Enfermagem Da U S P, 47(5), 1194-1201]

Want to learn more about the hormonal imbalance that causes chronic diseases? Discover practical protocols to guide your patients toward better health? 

During the Functional Medicine Certification Course, our trainers Michelle Leary-Chang, ND and Jonathan Nadal, ND, MSAOM will present about the biology of aging, the impact of stress, environmental factors, and nutrition on the hormonal system, and clinical effective protocols to treat hormonal imbalance and women’s and men’s health. 

Dr Michelle Leary-Chang is a researcher, presenter, and Functional Medicine Physician practicing general primary care and specialty men’s and women’s health. She completed training at the Institute of Women’s Health, American Academy of Anti-Aging Medicine (A4M), and the Institute for Functional Medicine (IFM) in areas of fertility, hormone management for men and women, anti-aging medicine, and metabolic weight-loss.

Dr. Jonathan Nadal earned a Doctorate in Naturopathic Medicine and a Master of Science in Acupuncture and Oriental Medicine from the National University of Natural Medicine. Dr. Nadal specializes in integrative medicine and advanced lab testing for the treatment of chronic and inflammatory conditions.


Adinoff B, Krebaum SR, Chandler PA, Ye W, Brown MB, Williams MJ. Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness. Alcohol Clin Exp Res. 2005 Apr; 29(4):517-27.

Al-Aridi R, Abdelmannan D, Arafah BM. Biochemical diagnosis of adrenal insufficiency: the added value of dehydroepiandrosterone sulfate measurements. Endocr Pract. 2011 Mar-Apr;17(2):261-70.

DeSantis, A. S., DiezRoux, A. V., Hajat, A., Aiello, A. E., Golden, S. H., Jenny, N. S., & … Shea, S. (2012). Associations of salivary cortisol levels with inflammatory markers: the Multi-Ethnic Study of Atherosclerosis. Psychoneuroendocrinology, 37(7), 1009-1018. doi:10.1016/j.psyneuen.2011.11.009

Griep, EN, Boersma, JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER. Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain. J Rheumatol. 1998 Jul;25(7):1374-81.

Lovallo W. R. (2006). Cortisol secretion patterns in addiction and addiction risk. International journal of psychophysiology : official journal of the International Organization of Psychophysiology59(3), 195–202.

Pires da Rocha, M. C., Figueiredo de Martino, M. M., Grassi-Kassisse, D. M., & Luiz de Souza, A. (2013). [Stress among nurses: an examination of salivary cortisol levels on work and day off]. Revista Da Escola De Enfermagem Da U S P, 47(5), 1194-1201. doi:10.1590/S0080-623420130000500025

Reddy, S. P., Prasad, M. G., RadhaKrishna, A. N., Saujanya, K., Raviteja, N. K., & Deepthi, B. (2017). Correlation between salivary cortisol levels and dental anxiety in children of smokers and nonsmokers. European Journal Of Dentistry, 11(2), 192-195. doi:10.4103/ejd.ejd_171_16

Vasiliadis, H., Forget, H., & Préville, M. (2013). The association between self-reported daily hassles and cortisol levels in depression and anxiety in community living older adults. International Journal Of Geriatric Psychiatry, 28(10), 991-997. doi:10.1002/gps.3912

Have Questions? Schedule a Short Call with Us