By now we all know that high cortisol is very undesirable. However, high cortisol isn’t the only issue here… it’s also the dysregulation of cortisol that’s a major concern.
There are three main ways of testing cortisol, namely, blood, saliva and urine.
If I were to test my hormones in general, I’d do a blood test first. This would include thyroid, gonadal and adrenal hormones.
If my cortisol wasn’t normal, I’d consider doing a salivary test, which would test only the free fraction of the cortisol in my saliva. The reason why saliva is not the primary go-to test for cortisol is because it doesn’t show you how much cortisol you’re producing in general. You could have sky high cortisol, but low free cortisol, and then you or the doctor might think you have low cortisol in total because of the low free cortisol, which would not be the case.
A salivary cortisol test is useful to test the 24 hour cortisol diurnal rhythm, the cortisol circadian rhythm, where your cortisol should be high in the morning and low in the evening. Ideally, you want to take your first measure right upon waking and then also 30 minutes after waking, as then your salivary cortisol is at its highest; the cortisol awaking response (CAR) reading. An exaggerated CAR could be indicative of increased perceived stress or being under stress constantly and low CAR is associated with reduced response to stress or waking; ACTH insensitivity. Roughly a 50-160% increase at the 30min mark is normal.
Blood testing for cortisol also tells you almost nothing because it’s just a snap shot in time. You might have felt very relaxed while waiting for the blood draws or very stressed and that could have given you a false reading.
Next up is the salivary & urinary test – the DUTCH test.
This test is very useful to see what is happening to you cortisol. It can test for your free cortisol as well as cortisol excretion.
It tests for salivary free cortisol and cortisone and then urinary tetrahydrocortisone (THE), tetrahydrocortisol (THF), αTHF, βTHF and βTHE. α and βTHF and βTHE are the 5α and β reduced metabolites of cortisol. The 5α & β-reductase enzymes are also largely involved in cortisol inactivation.
The problem with salivary and urinary cortisol is that it doesn’t show you how much cortisol you’re actually making, only the free fraction and at what rate you’re excreting it.
But nevertheless, it can be very useful. Let’s talk salivary cortisol first.
You’ll take about 5 measures during the day: right after you awoke, 30min later (to measure the cortisol awaking response), 60 min later, then one in the afternoon and the last one before bed in the evening.
Diurnal variation in cortisol
As you can see from this example, waking cortisol is normal, but there is no cortisol awakening response (CAR) and all the rest of the measures are low. This indicates low overall cortisol production and adrenal insensitivity to ACTH. Excretion metabolites are also low, which could indicate low overall cortisol production or just reduced excretion.
From this example you can see waking cortisol is low but there is an exaggerated CAR and then cortisol stays relatively high the rest of the day. This shows that the individual is hyper-responsive to stress and is also under a lot of stress during the day. The excretion metabolites are also high, so this could indicate adequate excretion, but just an excess production.
From this example you can see that free cortisol is fairly high and free cortisone is mid range, which could indicate reduced conversion of cortisol to cortisone during the day (due to hypothyroidism or inflammation), but more so later in the day, most likely due to a reduction in overall stress and an improvement in thyroid hormones.
Ideally you want a normal waking cortisol level, a 50-160% increase 30 min later, a 0-70% elevation 60 min later and then a gradual drop during the rest of the day.
You also want to see your cortisone pattern mimicking your cortisol pattern and the one not being higher or lower than the other.
Salivary cortisol patterns
Elevated cortisone with low cortisol during the day indicates an increased conversion from cortisol to cortisone. This is most common in hyperthyroidism and obesity. A high NAD:NADH ratio can also speed up this conversion. If you feel good and full of energy, then you don’t have to worry too much about it.
Low cortisone and high cortisol could indicate reduced conversion of cortisol to cortisone and this is most often due to inflammation and hypothyroidism. If you suspect it’s inflammation, have your high sensitivity (hs)CRP tested along with fibrinogen and homocysteine.
Low cortisone and low cortisol is most likely due to an excess of cortisol binding globulin (CBG) to protect the body against excess cortisol or reduced cortisol production, due to either low ACTH or ACTH insensitivity. If both are low, get a blood test to see actual cortisol levels.
High cortisone and high cortisol indicate high production of cortisol or reduced excretion.
This could be due to hypothyroidism, inflammation, high ACTH (or ACTH hypersensitivity) or an adrenal tumor.
Ok, let’s dive into the urinary markers. The most common markers are the THE and THF as well as the 5α and β reduced metabolites, depending on what test you get.
In a hyperthyroid state, you have increased deactivation of cortisol because the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 is increased by thyroid hormones. So in a hyperthyroid state you’ll have an increased ratio of cortisone:cortisol and THE:THF, whereas in the hypothyroid state, you’ll have an reduced cortisone:cortisol and THE:THF ratio.
Thyroid hormones also greatly increase the 5α-reductase enzyme, so you might have more αTHF as well compared to the hypothyroid state.
When total cortisol is high and cortisol metabolites are low, cortisol production might be adequate or in excess whereas excretion is reduced, most often due to low thyroid hormones. In this case you might simply want to boost thyroid function to increase excretion and maybe use an adaptogen to lower cortisol if in excess.
When total cortisol is high and cortisol metabolites are high, cortisol production is in excess whereas excretion is adequate. Focus on lowering cortisol.
When total cortisol is low and cortisol metabolites are high, not enough cortisol is likely being produced and most of it is being excreted. This could be either due to low ACTH levels or adrenal unresponsiveness or simply excess excretion due to elevated thyroid hormones. Again, if you feel good and have lots of energy, no need to worry about this.
An additional blood marker
Another marker you want to look at in blood tests is the DHEA-S (sulfate):cortisol ratio.
The normal range for DHEA-S it’s 280 to 640 µg/dL. The reference ranges vary a bit from lab to lab, but ideally, you want to be in the upper third of the range for both DHEA and DHEA-S.
The normal amount for cortisol in the blood in the morning is 140 to 690nmol/L (you want to be in the mid to upper range else you might experience fatigue, cravings, weakness, low motivation, etc.).
A DHEA-S:cortisol ratio of around 1 or more is ideal.
With a reduced ratio you stand a much greater chance of catabolism, mental disorders and suffering health symptoms.
For further references, read here to:
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