A position statement by the American Association of Clinical Endocrinologists (AACE) published in Endocrine Practice is aimed at raising awareness in the medical community about the risks of off-label use and misuse of hormones and dietary supplements.1

In recent years, there has been an increasing trend worldwide in dietary supplement use. These products are usually advertised as safe despite limited or no data to support their efficacy or safety, and they are often taken without the supervision of a healthcare provider.1

Major concerns regarding the unsupervised use of dietary supplements result from the lack of rigorous assessment before distribution; as such, they may contain undeclared pharmaceuticals or unregulated hormones.1

Adrenal Fatigue: Origins and Evidence

In his 2001 book entitled Adrenal Fatigue: The 21st Century Stress Syndrome, James L. Wilson, DC, ND, PhD, a naturopath and chiropractor, coined the term “adrenal fatigue,” which is claimed to be the result of overuse of the adrenal glands.2,3 According to this theory, adrenal fatigue develops secondary to chronic or extreme stress and is characterized by a constellation of common nonspecific symptoms, including physical and mental complaints.2,3


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A 2016 systematic literature review of adrenal fatigue including data from 58 studies concluded that the studies were highly flawed, providing conflicting results and inappropriate conclusions. The review authors concluded that the current evidence does not support the existence of adrenal fatigue or the usefulness of adrenal supplements.3

Off-Label Use of Adrenal Supplements

Although the Endocrine Society and the Hormone Health Network do not recognize adrenal fatigue as a legitimate medical condition, there are many websites that provide information on this topic, along with unfounded recommendations for self-diagnosis and options to purchase adrenal supplements to treat this condition. The proponents of adrenal fatigue support the use of glucocorticoids as well as over-the-counter supplements.1

While glucocorticoids are indicated for several medical issues, including adrenal insufficiency and inflammatory diseases, their use for the controversial diagnosis of adrenal fatigue is off-label. Studies to assess the effectiveness of hydrocortisone and fludocoritsone for patients with chronic fatigue syndrome have reported conflicting results and a randomized placebo-controlled double-blind study showed no beneficial effect of a combination of low-dose hydrocortisone and fludocoritsone on chronic fatigue.1

Adrenal supplements are used widely to treat patients who self-diagnose adrenal fatigue. Although they are frequently marketed as completely safe and hormone free, many of these supplements do contain unknown amounts of active hormones. Authors of a 2018 study that assessed whether 12 dietary supplements marketed for adrenal fatigue or adrenal support contained active hormones reported that pregnenolone was the most common hidden steroid in the samples (42%), followed by budesonide (25%), androstenedione (17%), 17-hydroxyprogesterone (8%), cortisol (8%), and cortisone (8%).4

Pregnenolone is an endogenous steroid and precursor in the biosynthesis of steroid hormones, including androgens, estrogens, and glucocorticoids. While there are claims that pregnenolone is an effective anti-aging treatment, there are no studies to support its use for adrenal insufficiency or deficiency.1

Dehydroepiandrosterone (DHEA) is another endogenous precursor steroid that is mainly produced by the adrenal cortex. Supplements containing DHEA are often marketed to support adrenal health and increase energy. However, a systematic review of DHEA supplementation in postmenopausal women did not support an improvement in wellbeing with DHEA supplement use.1

The potential complications of unsupervised and unknown exposure to steroid hormones include development of iatrogenic Cushing syndrome and a risk for adrenal insufficiency if these supplements are discontinued abruptly. Furthermore, the use of these supplements may delay the diagnosis and treatment of medical issues and can also worsen pre-existing medical conditions.1

Recommendations for Healthcare Professionals

In light of the risks associated with off-label use of hormones and supplements in patients without an established endocrine disorder and the lack of rigorous assessment of the safety and efficacy of dietary supplements, the AACE position statement recommends proper training for physicians to interpret laboratory test results in a more comprehensive way and to provide them with sufficient skills to be able to discuss with their patients the potential risks and benefits associated with off-label use of adrenal supplements.1

“Given the rise of health-care costs associated with tests and medications, practitioners should strive to be good stewards of the health-care system by minimizing the ordering of unnecessary tests and medications. Treatment recommendations should be based upon well-designed scientific studies. Finally, we should always keep in mind one of the most important principles of medicine, which is to do no harm,” concluded the AACE statement authors.

Disclosure: Several authors of the AACE position statement1 declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Irwig MS, Fleseriu M, Jonklaas J, et al. Off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements: risks and costs of a growing problem. Endocr Pract. 2020;26(3):340-353.

2. Wilson LJ. Adrenal Fatigue: the 21st century stress syndrome. US Smart Publication; 2001.

3. Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. 2016;16(1):48.

4. Akturk HK, Chindris AM, Hines JM, Singh RJ, Bernet VJ. Over-the-counter “adrenal support” supplements contain thyroid and steroid-based adrenal hormones. Mayo Clin. Proc. 2018;93(3):284-290.