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 may also be seen in hyperthyroidism and is suspected to be part of the chronic fatigue story as well. 


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:

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 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 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 oestrogen replacement tends to leave the free cortisol levels the same but blood cortisol levels can be much higher than normal.

I believe that this is because the HPA (hypothalamic-pituitary-adrenal axis or system) used free cortisol as its input. Oestrogen replacement raises cortisol binding globulin (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 will 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 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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