Adrenal Fatigue: Mythology, Physiology, and Resilience PART 1

by Camille Charlier

Adrenal fatigue is seriously relatable. You’re overworked and wiped out, craving sweets and salty fats, stressed, depressed, sex drive on the fritz. Sound familiar?

“Adrenal fatigue” is the notion that the adrenal glands get “overworked” from chronic stress and fail to produce essential hormones like cortisol. It’s a handy explanation for something a lot of us are experiencing. Burnout is real, but is adrenal impairment the root cause?

The smattering of scare quotes should clue you in. “Adrenal fatigue” is a faux-diagnosis. A medical myth. Internationally-renowned endocrinological societies reject the notion of “adrenal fatigue” categorically. The scientific community is unequivocal in their dismissal.

Ultimately, the idea that the adrenals “burn out” and lose their ability to produce cortisol in response to long-term adversity is based on a misunderstanding of physiology.

In particular, this faulty theory comes from a lack of understanding about the regulatory mechanisms that govern the resolution of the stress response. Yes, there’s a ton of research that shows chronic stress can devastate health, but no evidence that chronic stress causes deterioration of the adrenal gland itself.

In this series we’ll investigate the origins of the adrenal fatigue hype, and why it’s bogus. We’ll explore scientifically-validated explanations for fatigue, as well as legitimate pathologies of the adrenal gland. In the second installment, we’ll take a look at the physiology of the stress response, and mechanisms of its regulation and resolution. Finally, we’ll consider accessible lifestyle practices and essential oils for stress management, resilience, and well-being.

Adrenal Fatigue, an Origin Story

James L. Wilson, DC, ND, PhD is credited with coining the term “adrenal fatigue” in 1998. His intention was to “identify below optimal adrenal function resulting from stress and distinguish it from Addison’s disease.” Addison’s disease, also known as adrenal insufficiency, is a rare disease in which the adrenals fail to produce enough of the stress hormone cortisol, and sometimes aldosterone, a steroid hormone involved in sodium conservation. Addison’s is typically caused by mechanical damage to the adrenal gland, through surgical removal, injury, infection, autoimmune attack, or cancer.

In contrast to Addison’s, Wilson wants to make a case for dysfunction of the adrenal gland as a result of chronic stress. “Conventional medicine,” Wilson complains, “does not yet recognize it as a distinct syndrome.” That shouldn’t come as a surprise. There’s an utter lack of evidence to support Wilson’s claims, despite a surfeit of research on the topic (Seaborg, 2017).

What does Wilson stand to gain by making these claims? Bop over to his website, and ads pop up, emblazoned with bargains: “Save 10% on Doctor Wilson’s Original Formulations!” Click out of there and you get hit with the tagline: “Got stress? We’ve got the solution!”

Scroll down the page and there’s a handful of questions you can probably nod along with:

Has stress and pervasive tiredness hijacked your life? Is caffeine your best friend? Is sugar, fat and salt your primary food group?

Do you find it all just too much effort (even sex!)? Have you tried different fixes and maybe even different doctors to no avail? Do you even remember fun!?

If so you’re not alone and, most importantly, you’ve come to the right place.

Cringey copy, bold text, exclamation + question marks… ugh. Maybe I’m an incorrigible cynic, or perhaps I don’t even remember fun (!?), but I’m getting big whiffs of snake oil.

Waft your way through the “Adrenal Fatigue Questionnaire,” and if you’re anything like me, you can probably answer “yes, frequently” to many of the items (“I have experienced long periods of stress that have affected my well being”; “I get pain in the muscles of my upper back and lower neck for no apparent reason”; “I need coffee or some other stimulant to get going in the morning”). Mmmhmm. Good thing you can pick up some expensive products straightaway to solve all those pesky problems! With vigorous names like “Adrenal POWER Powder” and “Super Adrenal Stress Formula” you’re sure to perk those slacker glands riiiiight up.

Now that my eyes have finished rolling all the way back in my head, let’s get serious and take a look at what sources less invested in selling supplements have to say on the topic.

The Scientific Literature

In most cases, scientific literature is complex, findings are incomplete, no concrete conclusions can be drawn; each study offers more questions than answers. But what do we have here?

“Adrenal fatigue does not exist: a systematic review.” That’s the title of a 2016 article published in BMC Endocrine Disorders. BMC — BioMed Central — is a partner of Springer Nature, a highly respected German-British academic publishing company.

The purpose of this study was to determine the relationship between adrenal status and fatigue states. The authors wanted to know if fatigue was related to depleted adrenal function, and to confirm whether the methodologies used to assess fatigue status and adrenal function were valid.

There were 3,470 articles considered, and these were rigorously winnowed down to 58 papers acceptable for inclusion in the review. Of those that survived the cut, only ten citations used the specific expression “adrenal fatigue.” All ten papers were merely descriptive; no tests regarding the adrenals were actually performed.

Most papers used the term “burnout” instead of “adrenal fatigue” to describe the decrease in cognitive function, emotional exhaustion, and physical fatigue associated with overwork. “Burnout,” like “adrenal fatigue,” however, lacks any pathognomonic marker. In other words, there was no distinctive identifiable marker of pathology, and no observable impairment of the adrenal gland itself.

The studies that attempted to prove the existence of “adrenal fatigue” were a mess. The authors of this systematic review point out a few of the things wrong with them:

  • Many are purely descriptive, add no new data, and report on a condition (“adrenal fatigue”) that hasn’t been scientifically proven
  • Most studies were published in low impact journals — in other words, journals with a sketchy reputation in the research community
  • Inadequate and poor quality assessment of fatigue
  • Unsubstantiated methodology vis-à-vis cortisol assessment
  • “Lack of concern regarding validated adrenal assessment (as endorsed by endocrinologists)”
  • “False premises leading to an incorrect sequence of thinking and research direction”
  • “Inappropriate/invalid conclusions regarding causality” (Cadegiani & Kater, 2016)

Ouch. These scientists aren’t pulling any punches. “Invalid conclusions regarding causality” is a pretty clear KO for the pro-adrenal fatigue literature.

Likewise, the experts on the adrenals — endocrinologists, whole international societies of them 18,000 members strong — claim there’s no evidence for the existence of “adrenal fatigue.”

Take a look at the “Adrenal Fatigue” page on the Endocrine Society’s website. According to this global network of researchers and doctors, the symptoms typically attributed to “adrenal fatigue” are “common and non-specific, meaning they can be found in many diseases. They also can occur as part of a normal, busy life.”

Importantly, the society points out that the blood or saliva tests typically offered to test for adrenal fatigue are not “based on scientific facts or supported by good scientific studies, so the results and analysis of these tests may not be correct.” Let that sink in: the routine tests being performed to test for “adrenal fatigue” have no confirmed scientific basis (Hormone Health Network, 2020).

Cortisol: Rhythms, Reactions, and Analysis

Cortisol is complex. We don’t just have low or high cortisol. We have baseline cortisol levels, and cortisol levels that spike in response to stress. We have a natural circadian rhythm where cortisol surges when we wake up in the morning, then declines over the course of the day.

Accurately analyzing cortisol levels is an exercise in methodological precision. Scientists and clinicians can measure cortisol by testing saliva, urine, hair, and blood, but they must be stringent in their approach. Consider just a few of the factors that may influence test results:

  • Time of test relative to time of awakening. Was this self-reported? Objectively observed? Any variation in time elapsed changes the outcome of the test.
  • Acute stress impacts cortisol levels. The testing procedure itself may alter cortisol production. Laboratory or hospital environments may be experienced as stressful, and the venipuncture performed in blood tests may cause a stress response that confounds the results.
  • Type of test performed. Urine tests, for example, are performed over the course of a 24 hour period, and can give insight into cortisol patterns, whereas serum cortisol only gives a snapshot of levels at one point in time.
  • Test subjects’ work schedule. Shift work disrupts circadian rhythms and alters cortisol secretion patterns (Li et al., 2018).

Perhaps the most damning evidence against the myth of “adrenal fatigue” is that cortisol levels don’t correlate with fatigue states.

Folks with diagnosed fatigue and comorbid conditions don’t have lower cortisol levels compared with non-fatigued individuals.

In non-clinical populations, too, cortisol levels don’t correlate with fatigue states. What we do see in folks with fatigue and commonly comorbid associated conditions (multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic lower back pain, traumatic brain injury, and HIV) is alterations in the normal cortisol pattern, specifically the reduction of variability in cortisol levels in response to waking and acute stress (Powell et al., 2013).

It’s also worth noting that the production of cortisol varies wildly across individuals in response to stress. Indeed, a divergent response pattern has been observed across species, from fish and mice to pigs, sheep, and humans. Some individuals are considered “high responders” and secrete higher levels of cortisol in response to acute stress, whereas other individuals are classified as “low responders,” and secrete less. In other words, organisms exhibit an intrinsic, unique “set point” for cortisol reactivity (Hewagalamulage et al., 2016).

If you weren’t already convinced, here’s the nail in the coffin for theories of “adrenal fatigue”: both the mass of the adrenal glands and the number of adrenal cortisol‐secreting cells actually increase under stress (Karin, et al., 2020).

To sum it up, the research shows that cortisol levels don’t correlate with (let alone cause) fatigue states. Furthermore, there is no universal normal cortisol level. It’s the patterns of cortisol secretion over the course of the day, and in response to acute stress, that are clinically relevant. Finally, the adrenal gland responds dynamically to stress, and adjusts its mass and cellular make-up to meet stress-induced cortisol demand. That’s precisely the opposite of what “adrenal fatigue” proponents think is happening.

Treacherous Treatments

Despite a complete rejection of “adrenal fatigue” in the scientific community, it’s a wildly popular idea. A google search performed on April 22, 2016 by the authors of “Adrenal fatigue does not exist: a systematic review” with the search terms “adrenal fatigue” spat out 640,000 results. The media, healthcare providers, and even some doctors have bought into the idea of this alleged syndrome. Some medical societies (of dubious credibility) affirm the existence of “adrenal fatigue,” and recommend screening patients for it with Dr. Wilson’s aforementioned questionnaire. Those suspected of suffering from the syndrome are tested for serum basal (baseline) cortisol levels and salivary cortisol rhythm. If the test results seem off, patients are treated with corticosteroids.

A huge swath of patients have been prescribed corticosteroids (mostly the synthetic hormone hydrocortisone), by at least 24,000 health providers. This type of glucocorticoid “therapy,” however, can increase the risk of psychiatric disorders, osteoporosis, myopathy, glaucoma, metabolic disorders, sleep disturbances, and cardiovascular disease, even in low doses. It’s insidious. Corticosteroids typically promote a sense of well-being in just about anybody… albeit temporarily. Folks feel better and think the treatment is working, but the positive effects don’t last, and there are serious physical and mental health risks (Cadegiani & Kater, 2016).

Throwing “treatments” at patients — whether conventionally approved corticosteroids or dodgy “natural” pills —  without understanding the etiology of their symptoms is foolish, dangerous and… expensive.

Insurance companies are unlikely to cover the costs of scientifically unsupported substances. A bottle of Dr. Wilson’s “Adrenal Rebuilder,” for example, which is chock full of all the goodness of “porcine glandulars (gonad, adrenal cortex, hypothalamus, anterior pituitary)” will set you back $74.66 (You Save: $8.29 (10%)!). Take a look at the label, and you can see the hormones have been removed. That’s a good thing, considering that taking exogenous hormones can cause all kinds of problems. With the hormones removed, though, it’s unclear by what mechanism or magical thinking these mashed up pig parts are supposed to improve your (actually perfectly fine) adrenal function.

I went looking for an explanation on Wilson’s website and found this. Click that link if you want to be both addled and annoyed — it’s a big ol’ mess of unsubstantiated mechanistic handwaving. Scroll down and browse the bewildering array of “references” — a book on nutrition and oral degeneration authored by a dentist and originally published in 1939; biochemistry textbooks from the ‘50s and ‘80s; a conservation gardening and farming primer from 1993. Not a single citation more recent than 1997, no citation linked to the particular claims made in the article, no study performed on the actual impact of glandulars on adrenal function. Yikes.

Pig gonad pills. Food for thought, you know?

Fatigue — and Underlying Conditions — are Real

So your adrenals are fine, pig gonads are silly and expensive, and corticosteroids can cause long-term health problems. Cool cool, makes sense. But you’re still exhausted and can’t get out of bed and don’t know why and doctors don’t take you seriously and ugh you just want your life back. I have fibromyalgia, believe me, I get it.

Here’s the thing. Just because adrenal fatigue isn’t real doesn’t mean that there aren’t specific conditions (and lifestyles) causing exhaustion.

Folks experiencing intractable tiredness should absolutely be taken seriously. There’s no shortage of valid causes of fatigue, including allergies (food and environmental), autoimmunity, viral infections, anemia, depression, diabetes, hypothyroidism, cancer, sleep apnea, and poor quality or insufficient sleep, to name a few.

Certain symptoms highlighted on adrenal fatigue websites, like dizziness on standing, light-headedness, brain fog, and salt cravings, for example, might actually be a problem with low aldosterone, a hormone involved in sodium conservation (Cedars-Sinai, 2018). The obsessive (and unsubstantiated) fixation with the adrenals and cortisol in the alternative/complementary medicine community, and even in the mainstream, means that practitioners are missing other valid (and treatable!) conditions.

If you tick all the boxes of symptoms on the adrenal fatigue websites, don’t reach for your credit card to send for those sweet sweet glandulars, no. Hie thee to a physician and rule these conditions out.

Adrenal Insufficiency: A Legitimate Condition

“Adrenal fatigue” is not recognized by the Endocrine Society — or any other endocrinology society for that matter — but adrenal insufficiency is.

Primary adrenal insufficiency, also known as Addison’s disease, is typically caused by autoimmune adrenalitis. In this condition, the immune system attacks one or both adrenal glands, causing inflammation and impaired function. Other causes of adrenal insufficiency include malignancy, infection, and adrenal hemorrhage.

Symptoms of adrenal insufficiency include fatigue, weight loss, hypotension, and hyperpigmentation of the skin. Aldosterone is typically deficient, and lab results will reveal hyperkalemia (high potassium).

Standard treatment for the hypocortisolism that arises from adrenal insufficiency is glucocorticoid replacement therapy with synthetic steroid hormones like hydrocortisone (Thau, Gandhi, & Sharma, 2021).

Symptoms typically blamed on “adrenal fatigue” are frequently non-specific: folks are anxious and rundown, reaching for sweet and salty snacks, sleep is poor, getting out of bed is a chore, and the gut is a mess. In comparison, chronic adrenal insufficiency is characterized by a precise set of symptoms, and they don’t match:

Weight loss
Joint pain
Dry skin
Low blood pressure
Fatigue (Seaborg, 2017).

To diagnose adrenal insufficiency, an initial blood test is ordered to measure cortisol levels. A second test — the adrenocorticotropic hormone (ACTH) stimulation test — is used to confirm the diagnosis. In this test, a patient is injected with a synthetic compound that mimics the pituitary hormone ACTH (this is the hormone that signals the adrenals to produce cortisol), and cortisol levels are subsequently measured. If the adrenal glands don’t respond to stimulation by releasing cortisol, they may be malfunctioning. At present, this series of tests is the only method of accurately diagnosing adrenal insufficiency. Saliva tests are not considered reliable (Cedars-Sinai, 2018).

Repeat after me: “adrenal fatigue isn’t real.” Wonderful, now we can move on to what’s actually happening in the body with chronic stress. In our next installment, we’ll introduce the legendary hypothalamic-pituitary-adrenal (HPA) axis, and take a look at the role it plays in generating, regulating, and resolving the stress response. We’ll consider how it’s impacted by chronic stress (hint: it’s called “HPA axis dysfunction”), and the effect that has on health. Stay tuned!

This blog is part of a series on Adrenal Fatigue, you can read the second part here and the third part here.