Chris Kresser: It’s true. High free cortisol and low metabolized cortisol, hypothyroidism is one of the causes of that imbalance, and the reason for that is that thyroid hormones are peripherally required for metabolic clearance of cortisol. That means metabolizing free cortisol into tetrahydrocortisol and tetrahydrocortisone, which are the metabolites that are excreted in the urine. So if you see high free cortisol and low metabolized cortisol, then that can be a sign that the level of peripheral thyroid hormone activity is inadequate to complete the metabolic pathway. In fact, this ratio is actually being investigated as a way of diagnosing subclinical hypothyroidism. In other words, hypothyroidism could possibly show up in this fashion before it appears in the blood work, so it is something important to pay attention to.
Licorice supplementation can also cause this presentation because licorice increases the half-life of cortisol and prevents its conversion into cortisone, which is the less active form, so that can lead to high free cortisol levels. Inflammation is another thing that can cause this pattern, and then, as you mentioned, in some cases, liver issues could, although I tend to associate that more with the opposite pattern, with low free cortisol and higher metabolized cortisol. It can be both.
Also realize that, in some cases, high free cortisol and low metabolized cortisol can be normal and nonpathological. I think we discussed that in the course. I can actually even give you the exact slide number, although I’m not sure you even see slide numbers, but it was at the very, very end of DUTCH Test, Part One. I talked about how, in order to understand why this can be nonpathological, you have to understand how the test procedure works and where urine cortisol metabolites show up relative to when cortisol is produced. Cortisol maxes out in the early morning sample because overnight and early morning is when cortisol production is the highest, but remember that urinary metabolites lag behind cortisol production by about 90 minutes. If you check that last slide in DUTCH Test, Part One, you can see how the absolute max for cortisol that comes out in the early afternoon corresponds to the early morning cortisol if that’s missed. So if someone is relatively high in the early morning and then lower the rest of the day, the DUTCH test can miss a disproportionate amount of the metabolites that come from that morning surge, and that person will show up with having high free cortisol and apparently low metabolized cortisol even though that’s not the case. It’s kind of a tricky nuance of interpreting this testing, but if you see the high free cortisol and low metabolized, I wouldn’t just, on that basis alone, diagnose hypothyroidism, but I would filter through everything that I just told you and then look at other aspects of the case and other types of testing to determine if that person does have hypothyroidism.