Cortisol in the blood does NOT equal cortisol in the tissues - It's complicated - Aspire Natural Health

Cortisol in the blood does NOT equal cortisol in the tissues – It’s complicated

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One of the things I deeply enjoy my work is that it gives me the opportunity to constantly learn. It is my goal to look back on my treatment plans from 1-2 years ago and shake my head at how ignorant I was back then.

A student recently asked me how much time I spend studying and my answer was about an hour a day – between researching specific topics for patients, diving into subjects that have caught my attention, finding an area I’m weak on, reading a handful of blogs, books, and videos by experts, etc.

So in the vein of continuous learning, here’s a little something I recently uncovered while studying more about cortisol.


If you’re not up on cortisol, it’s one of our primary stress hormones secreted by our adrenals.

It’s definitely a Goldilocks hormone, too little is bad, and too much is also bad.

Chronic stress tends to derange the adrenal glands and disturb our cortisol leading to what is commonly called “adrenal fatigue”.

But, as with most things, it’s more complicated than that. Now we understand that it’s not just the cortisol produced by our adrenals, but certain tissues like fat, the liver, and other tissues have enzymes that can actually recycle cortisol and keep their cortisol levels up independent of what’s in the blood.

Whoa! That certainly complicates things…
“…intracellular cortisol levels within target tissues can be controlled by local enzymes. …thereby amplifying cortisol levels and glucocorticoid receptor activation in adipose tissue, liver and other tissues…there is evidence that it adjusts local cortisol concentrations independently of the plasma cortisol concentrations…[in mice] these data support the use of 11beta-HSD1 inhibitors [enzyme blockers] to lower intracellular glucocorticoid levels and treat both obesity and its metabolic complications….in human subjects…[inhibiting these enzymes and lower cortisol] enhances insulin sensitivity.”
“Obesity is closely associated with the Metabolic Syndrome, which includes insulin resistance, glucose intolerance, dyslipidemia and hypertension. The best predictor of these morbidities is not the total body fat mass but the quantity of visceral…fat [belly fat]. Glucocorticoids play a pivotal role in regulating fat metabolism, function and distribution… The role of glucocorticoids in prevalent forms of human obesity, however, has remained obscure, because circulating glucocorticoid concentrations are not elevated in the majority of obese subjects. Glucocorticoid action on target tissue depends not only on circulating levels but also on intracellular concentration…[cortisol in the fat tissue] is commonly elevated in fat depots from obese individuals. This suggests [that tissue cortisol is an important factor] in obesity and the Metabolic Syndrome…In adipocytes [fat cells], both antidiabetic PPARgamma agonists and LXRalpha agonists [diabetic drugs] significantly reduce 11beta-HSD1 mRNA and enzyme activity [the enzyme that is primarily responsible for recycling cortisol], suggesting that suppression of 11beta-HSD1 in adipose tissue may be one of the mechanisms by which these drugs exert beneficial metabolic effects.”

Measuring cortisol in the blood doesn’t necessarily tell you about how much is in the tissues because some tissues, particularly fat can recycle their cortisol and may have high levels inside the tissue even though it’s low in the blood.

High cortisol in the fat tissues seems to play an important role in the complications of obesity like high blood pressure, insulin resistance, and messed up cholesterol levels.

Diabetic drugs seem to, at least partly, block the enzyme that primarily recycles cortisol, lowering the amount of cortisol in the cells and lessening the bad things.

UPDATE:  Many other great docs out there have talked about how our idea of “adrenal fatigue” has evolved over the years, and while I still use the term, we recognize now that for many people it’s not really “low cortisol” that’s the issue, it’s a deranged “stress response”.

Most people don’t need more cortisol (although some do!), they just need to get everything balanced out.

I also rarely do cortisol saliva tests any longer, as for most people, I generally find they don’t provide valuable, actionable information that can’t be gathered elsewhere.


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Photo attribution –

Another Interesting post:

Women! Stress can mess up your gut bacteria as much as a bad diet



This Post Has 4 Comments

  1. Kerry says:

    Hello, thanks for this blog post, it’s really interesting and hard to find info like this! I’ve been trying to do my research on cortisol as I recently had a 24 hour hormone level test done (urine not blood) including Free Cortisol and Metabolised cortisol (THF+THE levels)
    Over 24 hours, my Free cortisol levels sat on the ‘low range limit’ which they said best represents the tissue levels… whereas my metabolised cortisol was within range. Would this indicate any kind of adrenal fatigue syndrome to you, in your opinion? Or would the normal metabolised range indicate it is functioning normally and tissue levels are just low for some reason not related to adrenal function…
    Sorry for the overly personal response and hope you have a moment to give your ideas!! keep up the good research..

    • Tim Gerstmar says:

      Hey Kerry,
      Thanks for the comment. Adrenal fatigue is a tricky term as you know – and tissues levels don’t necessarily reflect adrenal production of hormones. Low free cortisol is probably the most accurate indicator we have of the tissue levels of cortisol, so if your levels are on the low end of normal it could signify that your tissue cortisol is low and you have “adrenal fatigue” (but not necessarily because of low total production). Do these results make sense in light of how you feel?

      Hope that helps!
      Dr. Tim Gerstmar

  2. Sheri says:

    What is your opinion of saliva testing through the day vs blood for cortisol?

    Enjoying your blog, studying functional nutrition, naturally curious about everything

    Sheri .

    • Tim Gerstmar says:

      Hi Sheri,
      Good job educating yourself! It’s one of the keys to staying healthy.

      Cortisol in the saliva has been proven to have good relationship to blood cortisol levels and is easier to collect as it doesn’t require needles. Cortisol fluctuates over the course of the day so a single reading can be helpful but often doesn’t show us the true picture of what’s going on. I will sometimes get a morning blood cortisol if that’s what’s available as it can give us a clue.

      Having said all that, no test is perfect, they all have their downsides – so whether it’s blood, or saliva, or urine, none of us give us all the information we’d like to have.

      Hope that helps!

      Dr. Tim Gerstmar

      PS – IF we can help you with anything, please give us a call at 425-202-7849 or send us an email at

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