Clearing the Confusion about Cortisol

Cortisol tends to get a bad rap. And while it's true prolonged elevated cortisol levels are not good, cortisol in general is not bad. I hope to clear up some of the confusion about cortisol and "Adrenal fatigue" in this blog. 

Cortisol is a steroid hormone produced in the zona fasciculata within the adrenal cortex. It falls into the glucocorticoid class of hormones – meaning it plays a role in the metabolism of glucose.

Cortisol is released in response to stress and low blood-glucose levels. Cortisol will work to increase your blood sugar levels when they are low, suppress the immune system and to aid in the metabolism of protein, fat and carbohydrates.

Cortisol also follows a pattern of diurnal variation for circadian rhythm - meaning cortisol levels are highest in the morning after waking (you get a surge of cortisol within the first 15 minutes of waking, giving you energy) and slowly taper off throughout the day, until they reach their lowest point at about 3-4 hours after the onset of sleep (around 1am).

As you can see in the above example the patient's cortisol levels are above-range in the afternoon. Ideally all four measurements throughout the day would be in between the low and high range limits.

As you can see in the above example the patient's cortisol levels are above-range in the afternoon. Ideally all four measurements throughout the day would be in between the low and high range limits.

As I mentioned cortisol is released in relation to stress. This means cortisol is the hormone that is released when we enter ‘fight-or-flight’ mode. When we experience stress – real or perceived our cortisol levels rise. If we are truly in a fight-or-flight situation this greatly benefits us. We want our cortisol levels to rise when we are under stress, but we also want them to decrease again shortly after, as prolonged period of elevated cortisol do not benefit us.

Prolonged periods of high cortisol levels will lead to a wide variety of negative symptoms. Cortisol suppress the immune system, damages the hippocampus (leading to impaired learning), can lead to weight gain in the waist, and reduces bone formation.

When we are under prolonged periods of stress we begin to see problems with the HPA axis negative feedback loop. The hypothalamus is constantly being hit with signals telling it that there needs to be more cortisol in the body, so in response the hypothalamus releases more CRH. The pituitary then releases more ACTH and the adrenals in response attempt to produce more and more cortisol. The hypothalamus will then sense the increased levels of cortisol in the blood and try to down-regulate the production of CRH in response to the increased levels, but because the hypothalamus is still receiving other signals from the body telling it to make more cortisol, the hypothalamus begins to get confused. The hypothalamus listens to the signals telling it that your body needs more cortisol (because those are the life threatening signals), despite the adrenals basically trying to say to your hypothalamus “nope we’re good here – no more cortisol!!” (This is why the term ‘adrenal fatigue’ technically is not correct – it’s not that the adrenals are too tired to make cortisol, it’s that there is an issue somewhere in the HPA Axis. The only true “Adrenal Fatigue” is Addison’s Disease, also known as primary adrenal insufficiency, which is when the adrenals do not produce enough steroid hormones.)

This is when the person begins to enter the first phase of HPA Axis dysfunction. This first phase is called the acute phase. This is where we see high daily total free cortisol output – but the normal diurnal rhythm may be flawed, resulting in feeling wired at night, but exhausted in the morning. Other common symptoms in this phase include weight gain in the waist, increased blood sugar levels, increased inflammation in the body, immune system imbalances, trouble concentrating, and low libido to name a few.

Eventually the body can no longer sustain the high free cortisol levels, and free cortisol (not to be confused with total cortisol) levels start to drop. This is what we consider the compensatory phase of HPA Axis dysfunction. Total output of cortisol for the day is technically “in-range” in this phase but this is where symptoms really begin and the person starts to not feel well. We see circadian rhythm issues, sex hormone imbalances show up on lab work, neurotransmitters imbalances, elevated Cortisol to DHEA ratio, decreased memory, loss of muscle mass, along with the symptoms from the acute phase.

If someone does not work to decrease their stress levels, and increase their metabolic reserve they may enter the third phase, which is the exhaustion phase. In this phase free cortisol levels are low and generally the person is very fatigued. Symptoms of decreased free cortisol include fatigue, frequent illness, joint pain, muscle pain, low blood pressure, dizziness, weakness, increased thirst, digestive issues, depression/low mood and hypoglycemia. Normal every day activities like going to work or taking out the trash may seem overwhelming due to fatigue.

The three phases of HPA Axis Dysfunction

The three phases of HPA Axis Dysfunction

In these three phases what we are actually measuring is FREE cortisol. Free cortisol only makes up about 1% of the total cortisol output by your body, but is the active form of cortisol.

Cortisol can circulate in the body bound to a carrier protein, or it can circulate free. Bound cortisol does not have the ability to act in the body (it does not play a role in the important functions listed above – only free cortisol does).  We use free cortisol to assess the up and down daily cortisol pattern, but since free cortisol only makes up about 1% of the total cortisol output, it does not tell us how much cortisol is actually being made in the body. (Therefore when running lab work to assess your cortisol levels it is important to measure metabolized cortisol levels as well - which is another reason the term "adrenal fatigue" is technically incorrect. Total cortisol output may actually be in-range or even high, while free cortisol levels are low. So the adrenals actually aren't fatigued at all.)

Metabolized cortisol is the sum of three cortisol metabolites. Hormone metabolism is the process of hormones being processed by the body through the liver through phases I and II of detoxification, before they can be excreted out of the body. As the hormones undergo this process they are turned into metabolites. Metabolized cortisol gives us a better idea of total cortisol output from the adrenal glands.

Cortisone is the inactive form of cortisol. But don’t confuse cortisone with hydrocortisone. Hydrocortisone is cortisol. If you take a hydrocortisone supplement (usually in the form of a cream), you are taking active cortisol. However cortisone, the inactive form of cortisol, is converted from cortisol via an enzyme located in the kidneys, saliva glands and colon. Since cortisone is the inactive form of cortisol, it is not able to do all the important functions cortisol is able to, like balancing blood sugar and fighting against stress. Cortisol CAN be reactivated back into cortisone, through an enzyme located in the liver, fat tissue and nervous system - which is why it's important to measure cortisone levels as well!

So how do you begin to regulate your cortisol levels so they are in a healthy and optimal range again?

The first suggestion I have is learn to listen to your body. Does something feel off? Do you have any of the symptoms listed above? We live in a society where we glorify hustling and multi-tasking. We think pushing through it is what we are supposed to do, but that is only hurting us in the long-term.

Prioritize sleep and stress-reduction. Plan relaxing activities for yourself and make it a priority – whatever that means for you, whether it’s meditating, taking a bath, going for a walk, turning your phone off for a few hours or watching a comedy. I suggest to all my clients to find a way they can reduce stress daily – something that can be done easily without much effort each day, and also find something they can do weekly that may take up more time. Living in the 21st century it’s hard to reduce stress, I know. But you only get one body, make treating it right a priority.