Cortisol Results Inconsistent Between Saliva Testing and Blood Testing

This post may help to explain why sometimes we might see an inconsistency between the result for an 8:00 am morning cortisol blood test (which includes free and bound cortisol) compared to the free cortisol measured in a cortisol saliva test.

It is very important to realise that cortisol saliva testing and cortisol blood testing measure entirely different things. A cortisol blood test measures all the cortisol contained in the blood, i.e. both the free/unbound cortisol and the cortisol bound to protein (cortisol binding globulin or CBG). A cortisol saliva test only measures the free cortisol. In some cases, a person may have very high or very low bound cortisol (the non-free portion). This can make the cortisol blood test result appear either high or low in the range compared to cortisol measured in saliva.

Clearly, every situation is different and the entire history and situation with an individual needs to be taking into account.

The link explains that the amount of cortisol produced and the amount of free cortisol available can be very different in some scenarios. Measuring both allows for insight into the rate of cortisol clearance/metabolism. Here are two examples:

1) Higher levels of metabolised cortisol (compared to free cortisol) are often seen in obesity where adipose tissue is likely pulling cortisol from its binding protein and allowing for metabolism and clearance. The adrenal gland has to keep up with this cortisol sequestering and excretion, so cortisol production is often quite high (as seen in an 8:00 am morning cortisol test or in the levels of metabolized cortisol if using the Dutch test). This insight is quite helpful for those looking to lose belly fat and suspect cortisol/stress is a major factor. These patients are often misdiagnosed as having low cortisol production when only free cortisol is measured because high blood cortisol and low saliva cortisol is seen.

Increased cortisol clearance (and low free cortisol in saliva and urine) may also be seen in hyperthyroidism and is suspected to be part of the chronic fatigue story as well. 

and

2)  In patients with low thyroid, the opposite pattern is often seen. When the thyroid slows down, or if there is peripheral hypothyroidism where free T3 cannot get into the cells, the clearance (or metabolism) of cortisol through the liver slows down. As a result, free cortisol starts to increase and may show up elevated. Note: this is a pattern I have seen multiple times with thyroid patients.  It is useful to know, as assuming on-going tissue-level hypothyroidism may be the best way to go forward when low/normal blood cortisol and high saliva cortisol is seen. Simply assuming that the saliva test is correct and the blood test is not may be wrong sometimes. 

Here is the link:
https://dutchtest.com/2017/09/25/metabolized-versus-free-cortisol-understanding-the-difference/

The bottom line is that I am a great believer in testing both free cortisol in saliva and total cortisol in blood at 8-9:00 am, as you get the whole picture. Relying on free saliva cortisol only is not sensible. There can be inconsistent results between blood cortisol testing and saliva cortisol testing and this needs to be assessed properly. This position is very clear in all my books, including the latest one, The Thyroid Patient’s Manual.

Using the same test laboratory all the time is equally important if you want to see how cortisol has changed after making any adjustments to your regime. Different labs can have extremely different results.

It is also possible that a lot of patients who have apparently high cortisol from a saliva test are being given guidance to lower the free cortisol with adaptogens, when what they really need to do is to fix the tissue hypothyroidism with more thyroid hormone. In some cases, the person might have low total cortisol (a blood test at 8 or 9:00 am will show this). In this case, raising total cortisol with CT3M might also help.

I think the above is an insight worth knowing about. It also emphasises the importance of both blood and saliva testing. There can be inconsistencies between the two cortisol testing methods. It at least should prompt people to think harder about the cortisol test results and question what is really going on.

Other causes of inconsistent cortisol blood and saliva test results:

A. The use of natural progesterone creams can corrupt the results in many saliva testing labs. The progesterone molecule is so similar to cortisol that many labs cannot distinguish between the two and show higher cortisol as a result. Even stopping the cream/gel a few days before might not stop this as it sits in the tissues.

B. The use of any HC cream can do the same and inflate cortisol saliva test results.

C. Those patients on oral oestrogen replacement can have much higher cortisol in blood tests, than in saliva tests. The reason for this is that oestrogen increases cortisol binding globulin (CBG) and falsely elevates any cortisol blood test. So, patients who need to do a cortisol blood test or a Synacthen test (ACTH Stimulation test) need to be off oestrogen replacement for 8 weeks prior to the test. The oral oestrogen replacement tends to leave the free cortisol levels the same but blood cortisol levels can be much higher than normal. Note: transdermal oestrogen replacement does not affect CBG. See: https://pubmed.ncbi.nlm.nih.gov/17492949/

I believe that this is because the HPA (hypothalamic-pituitary-adrenal axis or system) uses free cortisol as its input. Oral oestrogen replacement raises CBG thus binding more of the free cortisol to protein. The HPA then responds by requesting the adrenals to make more cortisol to compensate for higher CBG. The net result is that all cortisol blood tests can show falsely inflated cortisol levels. Whilst the free cortisol in saliva tests remains unaffected. Note: the same thing can occur in those women with unusually high oestrogen levels.

D. Gene mutations can lower cortisol binding globulin, thus increasing free cortisol but lowering total cortisol.


I hope that you found this article interesting and useful.

Best wishes,

Paul
 

Paul Robinson

Paul Robinson is a British author and thyroid patient advocate. The focus of his books and work is on helping patients recover from hypothyroidism. Paul has accumulated a wealth of knowledge on thyroid and adrenal dysfunction and their treatment. His three books cover all of this.

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4 Comments

  1. Eve on 20th November 2022 at 4:02 pm

    Hi Paul,

    Thank you for this useful blog on cortisol.

    I was wondering why one can have normal blood cortisol (551, range up to 800), while salivary cortisol is low in range?
    My FT3 is high in range along with FT4 (FT3 78%, FT4 75% – measured 24hrs after NDT) and I’m curious if that could be depleting cortisol from saliva? My endo measured also my blood cortisol 2.5 hrs after taking NDT and it was over range, while it was normal over midrange in the morning before medication.
    I currently resemble symptoms of thyroid overmedication (tremors, shaking, hunger, overheating etc.).

    Thank you for all your posts, they are very helpful!

    • Paul Robinson on 20th November 2022 at 4:19 pm

      Hi Eve,

      One immediate observation is that with high FT4 and high FT3, often there can be high reverse T3. So rT3 ought to be tested as you might need to have the NDT reduced and some T3 added – so that you have less FT4 available to go into rT3. This is worth checking as you might not have the available FT3 that you think you have.

      Over-medication symptoms can be caused by other things. For instance, low free cortisol causes adrenaline to be released – the same symptoms. In addition, excess rT3 clearing can also cause this type of symptom to occur.

      Also, estrogen when high or estrogen dominance can lower saliva cortisol. The blog post discusses points A, B and C at the end that might be relevant.

      Hope this helps.

      Best wishes, Paul

  2. Lotty on 19th February 2024 at 1:52 pm

    This is very interesting as I have just had a normal blood test but a saliva test shows I have chronic HPA axis dysfunction and low DHEA. I use a Symbicourt asthma inhaler, hrt patches, testogel, ompeprazole and Armour Thyroid – and those hormones are now optimal. All blood tests came back normal apart from raised platelets.
    I have all the usual symptoms of low cortisol and am losing weight but also palpitations and high pulse rate. Would adaptogens be sufficient to bring my levels up? Many thanks.

    • Paul Robinson on 19th February 2024 at 2:20 pm

      Hi Lotty, no, adaptogens all tend to lower cortisol. There is a lot of daft information on the Internet and the info on adaptogens is a good example. Some say that adaptogens will lower high cortisol and raise low cortisol. But that would imply that they have some kind of brain or computer and can make a decision over what to do. It makes no sense. My experience with adaptogens is that they are quite good at lowering high cortisol but for low cortisol they just make things worse.

      I would use some of the Armour to attempt to use my CT3M protocol (see the Recovering with T3 book). An alternative can be trying to use LDN. However, one of the biggest causes of low cortisol is insufficient FT3 levels in the night.

      The other thing is what is normal for thyroid results? Most people need to be in the right place in the range for FT3 for them – not just in the range. So, again more FT3 might help:
      https://paulrobinsonthyroid.com/research-shows-free-t4-and-free-t3-ranges-for-individual-thyroid-patients-are-less-than-half-as-wide-as-the-wide-population-laboratory-ranges/

      Best wishes, Paul

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