Written by APD Holly Baxter
June 21st 2019

‘Adrenal Fatigue’ is a nonsense term used by some doctors, healthcare providers and many fitness professionals to describe symptoms of extreme fatigue brought on by regular physiological and psychological stress, which allegedly leads to increased cortisol levels.  Adrenal fatigue has also been used to provide justification for the inability to lose weight, with no pathophysiological markers to explain such symptoms.

To date, science does not support the notion of adrenal fatigue as its most often explained – that stress causes high cortisol, which causes fatigue, inability to lose weight and other symptoms.

With this being said, it is also important to mention that ‘Adrenal Fatigue’ is not a recognized condition by either the endocrine or medical communities, so lets set the facts straight.

This article discusses all the facts you need to know about the endocrine system and the hormones produced by the adrenal glands.

What is HPA Axis Dysfunction?

HPA stands for Hypothalamus Pituitary Adrenal Axis, and includes;

Hypothalamus

The hypothalamus is a region of your forebrain that unites the automatic nervous system and the endocrine system with the pituitary gland. The hypothalamus is important for maintaining homeostasis by regulating functions such as sleep, our emotions, body temperature, hunger, thirst and more.

Pituitary Gland

The Pituitary gland is a pea size gland found at the base of the brain. It is considered the master gland as it regulates other endocrine glands.

Adrenal Glands

The adrenals sit above the kidneys and these produce important stress hormones such as cortisol, epinephrine (aka adrenaline), aldosterone, and norepinephrine.

The Anatomy of the Adrenal Glands

Let’s start with the anatomy of the adrenal glands so you have a visual representation of exactly what we are talking about.

An adrenal gland is made of two main parts:

  1. The adrenal cortex
    This is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.
  2. The adrenal medulla
    The medulla is located inside the adrenal cortex in the center of an adrenal gland. It produces a number of “stress hormones,” including adrenaline. It also produces Aldosterone, DHEA and Androgenic Steroidsm, Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline).
The adrenal cortex and adrenal medulla are enveloped in an adipose capsule that forms a protective layer around an adrenal gland.

Hormones of the Adrenal Glands

adrenal Gland

The role of the adrenal glands is to release certain hormones directly into the bloodstream. Many of these hormones are responsible with how the body responds to stress, and these are vital for our existence. Both parts of the adrenal glands, both the adrenal cortex and the adrenal medulla perform distinct and separate functions.

The Adrenal Cortex

Each zone of the adrenal cortex secretes a specific hormone.

One of the key hormones produced by the adrenal cortex is cortisol.

Cortisol

Cortisol often gets a bad rap amongst hormones, however it actually has a number of very important regulatory roles which are often misunderstood or taken out of context. Cortisol is a gluco-corticoid hormone which is produced by the zona fasciculata.

It helps control many functions including the body’s use of fats, proteins and carbohydrates during times of stress, it helps suppress inflammation as well as helping to regulate our blood pressure.

This hormone also controls our sleep/wake cycle, otherwise known as the circadian rhythm.

During a fight or flight response, when our body senses stress, cortisol is released into the blood stream, which in turn increases our blood sugar levels by stimulating gluconeogenesis. This then helps provide energy in emergency situations. During this fight or flight response, cortisol can alter or shut down other functions that are not useful during a stressful event such as your digestive or reproductive systems, your immune system, or even certain growth processes. If cortisol wasn’t tightly regulated, these important processes would not take place during times of stress, and this demonstrates why it is very important for our cortisol levels to rise in these types of situations.

How do Adrenal Glands Work to Produce Cortisol?

Adrenal glands produce hormones in response to signals from the pituitary gland in our brains, which reacts to signaling from the hypothalamus, also located in the brain. This is referred to as the HPA axis (hypothalamic pituitary adrenal axis).

As an example, for the adrenal gland to produce cortisol, the following cascade of events occurs:

  • The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH).
  • ACTH then stimulates the adrenal glands to make and release cortisol hormones into the blood.
  • In normal healthy individuals, both the hypothalamus and the pituitary gland can sense whether the blood has the appropriate amount of circulating cortisol. If there is too much or too little cortisol, these glands respectively change the amount of CRH and ACTH that gets released. This is referred to as a negative feedback loop. This is comparable to the way an air conditioner regulates the temperature in our homes. When the temperature exceeds the set room temperature, the air conditioner switches on and starts circulating cool air until it is back to the set temperature. If the temperature of the room gets to cool, the air conditioner switches off. This is a great example of how cortisol in the body is regulated in a similar feedback manner.

What are the normal ranges for Cortisol?

Cortisol levels are naturally elevated in the morning and lower in the evenings, but these ranges are highly regulated.

Molecules of Cortisol Hormone

Reference ranges for blood plasma content for free cortisol
Morning
Time 9am
Lower limit 140 nmol/L
Upper limit 700 nmol/L

Reference ranges for blood plasma content of free cortisol
Evening
Time 4pm
Lower limit 0 nmol/L
Upper limit 275 nmol/L

What are the disorders of the Adrenal Glands

The two common ways in which adrenal glands cause health issues are by producing too little or too much of certain hormones, which leads to hormonal imbalances. These abnormalities of the adrenal function can be caused by various diseases of either the adrenal glands or the pituitary gland.

Overactive Adrenal Glands

Sometimes, adrenal glands may develop nodules that can produce too much of certain adrenal hormones. Nodules 4 centimeters or larger and nodules that show certain features on imaging, increase suspicion for malignancy. Both benign and cancerous nodules may produce excessive amounts of certain hormones including cortisol, which is referred to as a functional nodule.

Elevated cortisol level caused by nodules are referred to as a condition called Cushing syndrome. This can lead to rapid weight gain and fatty deposits in certain areas of the body such as the face, below the back of the neck (often referred to as a buffalo hump) and in the abdomen. We don’t have a great explanation as to why this phenomenon occurs. Perhaps it has to do with cortisol’s role in lipolysis. You see, cortisol increases the rates of lipolysis (liberation of free fatty acids from adipose tissue) which increases the concentrations of free fatty acids in the blood, however, when this is combined with a caloric surplus (as is often the case in people with high cortisol, as stress can cause overeating) these free fatty acids are not oxidized and must be re-esterified (re-stored) back into adipose tissue. Perhaps they are being preferentially re-stored in these specific sites. This is my best guess based on the current literature.

Other symptoms of Cushings Syndrome include fatigue, muscle weakness, easily bruised skin, high blood pressure and diabetes. Elevated cortisol levels can also reduce bone formation, which can lead to long-term development of osteoporosis due to decreased calcium absorption in the small intestine.

What else can cause elevated Cortisol Levels ?

Excess cortisol production can also be triggered by overproduction of adrenocorticotropin hormone (ACTH) by a benign tumor in the pituitary gland or tumor elsewhere in the body. Another common cause of Cushing syndrome is excessive and prolonged consumption of external corticosteroids, such as prednisone or dexamethasone, which are prescribed to treat various autoimmune or inflammatory diseases (e.g., lupus, rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis, etc.). These exogenous forms of cortisol also stimulate appetite, which is one of the reasons we often see people with these above mentioned conditions also experiencing sudden weight gain.

What if you’re under constant stress?

As we have established, it is normal for our cortisol levels to rise and fall throughout the day, this is called the diurnal variation.

Even if you are under a high amount of stress, after a stress or danger has passed, cortisol levels will fall back to within then normal physiological ranges, along with heart rate, blood pressure, and other body systems that are affected during a stress response.

Some of the symptoms of elevated cortisol include anxiety and depression, headaches, memory and concentration problems, problems with digestion, as well as trouble sleeping, and these can indirectly effect our ability to lose weight.

For example, studies have shown that even one night of sleep disruption, which is often be caused by stress, can interfere with our hunger and appetite regulation and the production of hormones leptin and ghrelin. In a situation where you are trying to diet, poor sleep and the accompanying changes in hunger hormone signaling may result in extra calories being consumed throughout the day. Dieting, irrespective of stress, has been shown to result in sleep disruptions due to changes in hunger hormone signaling, so it is easy to see how the association with the stress hormone cortisol and weight gain can came about, but it is not a direct causal relationship, rather an indirect relationship between cortisol and weight gain.

Underactive Adrenal glands, Adrenal Insufficiency

Adrenal insufficiency is a very rare disorder. It may be caused by disease of the adrenal glands (primary adrenal insufficiency, known as Addison’s disease) or by diseases in the hypothalamus or the pituitary (secondary adrenal insufficiency). It is the opposite of Cushing syndrome and is characterized by low levels of circulating adrenal hormones.

The symptoms of Addison include, loss of appetite and weight loss, muscle weakness that grows worse, fatigue and feeling tired all the time, diarrhea, nausea and vomiting, low blood pressure, darkening of skin (only in primary adrenal insufficiency) and abdominal pain.

The causes of primary adrenal insufficiency may include autoimmune disorders, fungal and other infections, cancer (but rarely), and genetic factors such as congenital adrenal hyperplasia. Children who are born with this disorder are missing an essential enzyme necessary to produce cortisol, aldosterone or both.

Although adrenal insufficiency usually develops over time, it can also appear suddenly as an acute adrenal failure (adrenal crisis). It has similar symptoms, but the consequences are more serious, including life-threatening shock, seizures, and com, which may develop if the condition is left untreated.

Is ‘Adrenal Fatigue’ Real?

If high cortisol is associated with weight gain, then let’s examine the claims. If adrenal fatigue was a condition of elevated cortisol, then we already have a name for it, that is Cushings Syndrome. Secondly, you can easily have your cortisol tested via a blood or saliva test to determine if you have some sort of adrenal dysfunction, rather than relying on a list of nebulous symptoms to determine. The list of symptoms for ‘adrenal fatigue’ are purposefully nebulous and include symptoms that could be explained by a myriad of different reasons. I’m not saying that someone cant be experiencing a range of symptoms, what I’m saying is that if these issues are caused by elevated cortisol levels, then this would show up on a simple blood or saliva test.

Many ‘adrenal fatigue specialists’ will insist that you rely upon their vague list of symptoms in order to diagnose ‘adrenal fatigue’ rather than just take a simple test. These symptoms could be identified with by the majority of people: weight gain, fatigue, sleep problems, inability to lose weight, etc.

If you are experiencing some of these symptoms and think high cortisol is the culprit, then I encourage you to get a blood or saliva test and consult with an endocrinologist if your cortisol levels are truly high, who can help you regulate your hormones. Please don’t waste your money seeing a naturopath who claims they can cure your ‘adrenal fatigue’ with expensive supplements that they just also happen to sell.

What is more likely to be the cause of these symptoms?

It is unlikely the conditions I’ve discussed above are the case for the majority of the population. Cushings Syndrome is not a common disorder an affects less than 1% of the US population. If you are suffering from a high amount of stress, i.e. an exhausting work schedule, long hours, difficult relationships, all these factors can impact our sleep. Sleep disruptions (lack of sleep and reduced sleep quality), has been shown to cause changes in circulating hunger hormones leptin and ghrelin. This then affects our ability to regulate our appetite, which indirectly effects our ability to lose weight by excess food consumption and increased caloric intakes. In the acute setting, stress can result in undereating, but in chronic situations, high levels of stress can lead to the development of negative eating behaviors such as overeating or binge eating.

The key to managing weight is by and large about creating a caloric deficit, by ensuring that we are burning more energy than we consume. When it comes to stress, this means trying to make sure we identify and minimize stress, so we are not tipping the scales in favor of increased energy intakes and decreased energy expenditure.

As you can see, the adrenal glands play an important role in our day to day function, specifically regarding stress. However, it is important to realize that the subsequent rise in cortisol and other hormones of the adrenal glands, are tightly regulated, and for the otherwise healthy individual, after a stress has passed, these hormones return to their normal physiological ranges.

If you would like more information about this, please feel free to email me hb@biolayne.com

References:

https://www.hopkinsmedicine.org/healthlibrary/conditions/endocrinology/adrenal_glands_85,p00399

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