Stress Reduction (Part 1): You Can’t Manage What You Don’t Measure
Well, the busy, stressful holiday season has begun and I have been tasked with writing about Stress Reduction for this month’s posts. Now there are without a doubt many hundreds, nay thousands, of health-centred blogs in North America. I’m sure every last one of them has dealt with holiday season-induced stress at some point and advises the same things: pay attention to your sleep, exercise regularly, don’t overdose on sugar and alcohol, stay hydrated (100-proof rum does NOT count!)
If you’re reading this blog, you probably already know all this stuff. And truth be told, we should be thinking about stress year-round. Not just during the holidays. Also, I have repeatedly mentioned hormones in other posts so I felt it was time to get down into specifics.
So. I’m going to devote this post to focusing on the stress hormone cortisol as part of the overall strategy of testing a wide range of hormones in one 24-hour cycle. When it comes to stress, the cortisol pattern throughout a 24-hour cycle can be far more informative than one sample taken at one time point. Identification of aberrant cortisol patterns can go a long way toward informing what treatments might be helpful for stress-related problems. I’ll discuss basics of testing and then identify interesting cortisol patterns that may show up. In a second post later this month I’ll discuss what you can do about these patterns and how they might fit in a larger framework.
I realize that this information is arriving a little too late to be helpful over the next few weeks but it will be good to have at your fingertips to kick off 2023. I promise. Otherwise, you can send me a lump of coal next Christmas.
There are numerous ways to measure hormones: blood, saliva, urine, hair, sweat. For many years, my laboratory, Rocky Mountain Analytical, focused on saliva but in the last five or so years, I came to have a greater appreciation for the wealth of information offered by urine testing as it especially helpful for looking at cortisol patterns.
Cortisol is produced in pulses throughout the day. It’s distributed to tissues, delivers its messages and is then rapidly broken down into inactive cortisol metabolites and excreted mostly in urine. This seems wasteful but it enables the adrenal glands to rapidly adjust cortisol output to changing demand. Measurement of the cortisol metabolites has been shown to reflect production of cortisol (Prezio 1964, Salehi 2005). A good analogy would be to look in someone’s blue bin to determine how much stuff they order from Amazon by counting wrappers and cardboard boxes.
The other cortisol measurement that is important in urine is free cortisol, which is thought to reflect what the bodily tissues are exposed to at any given time. It’s the difference between peering into the blue bin every few hours versus peering into it every other day or so. Another analogy might be that the cortisol metabolites are your salary and free cortisol is what’s in your wallet or purse at any given time.
The following graph represents a profile of free cortisol constructed from 4 urine samples collected across 24 hours. The Waking(A) sample reflects all the urine made during sleep and up to the point of waking-typically 8 hours. The Morning(B) sample reflects the urine produced in the two hours after waking. The Afternoon(C) sample reflects the urine produced in the two hours before the evening meal and the Night(D) sample reflects the urine made in the two hours before sleep.
Note: This plotting format is used in the report for a 4-point urine steroid test, the Dried Urine Test for Comprehensive Hormones or DUTCH, offered by Precision Analytical Laboratory in Oregon. This is the go-to urine test used in the EvolveWell Clinic. In addition to cortisol profiling, the DUTCH offering yields the same information on many other hormones that you would get by sending a sample of all the urine you voided (and carefully saved) in a 24 hour period. This approach is inconvenient and not feasible in many cases.
Per the above, on waking, free cortisol output surges briefly (AàB) and this surge is called the Awakening Response. While you were sleeping your brain was already getting ready to start a new day by making cortisol. When you become awake and realize it, your body produces an extra little “jolt” of cortisol to get you on your feet and en route to the coffeepot.
Free cortisol then declines steadily throughout the rest of the day until bedtime (B->C->D). When you have been asleep for several hours, free cortisol reaches a low point (not shown) and then begins to rise again toward waking the next morning and the cycle starts all over again.
Exercising artistic license here, the below graph with the lilac-shaded area at the right takes the Morning point (A) point and “replays” it at the right end of the graph as (A*). The line drawn from the Night(D) point to (A*) helps you better picture what is going on with your free cortisol while you’re sleeping.
It’s important to know that 4-point urine testing is the only way you can find out how much cortisol you’re making during sleep. Point samples of saliva and blood aren’t feasible and don’t reflect what’s really going on. Too much or too little cortisol production overnight affects sleep quality, metabolic health and how you feel when you wake up in the morning.
Repeat after me: “I am supposed to make cortisol while I sleep.”
The foregoing might be difficult to digest for some people who aren’t used to looking at graphs. Just remember that the Waking or “A” point should be higher than the Night or “D” point indicating that free cortisol production overnight increased beyond what was being made at bedtime. Similarly, the Morning or “B” point should usually be higher than the Waking or “A” point, indicating that there was an awakening surge of free cortisol.
Don’t worry. There isn’t going to be a test at the end of this post and the practitioners at EvolveWell are willing and able to walk you through the interpretation of your urine test report, should you choose to do one.
I’m now going to display various common free cortisol curves that are often seen in clinical practice with the DUTCH urine test and make a few brief comments for each. The patterns will be discussed in more detail next post, along with treatment approaches, as mentioned. Note that on the actual reports you see only the A,B,C and D points. If you draw a line back from point D to Point A, that line should slope up to the left.
The following profile indicates that there is very little free cortisol being produced as the patient line hugs the bottom end of the normal range limit curve. Nevertheless, there is a rise in free cortisol overnight and an awakening surge in the morning. Some patients who display this profile may feel fine: others may display this profile and feel terrible as will be explained next post.
This next profile reveals that the patient has a large amount of free cortisol and I refer to the profile as a “Redliner” since the patient points all lie above the high end of the normal range. There is a very large increase in free cortisol overnight accompanied by only a small increase after waking. This patient may have some significant metabolic issues.
I call the next pattern a “Sprinter” because all the free cortisol production is concentrated in the period from waking to bedtime. Little cortisol is made overnight. The patient may literally leap out of bed, “sprint” through the day and collapse into bed that night.
The Loss of Regulation pattern indicates just that: little or no variation across 24-hours. This pattern can have serious long-term implications if not rectified.
I refer to this last pattern as “Early Takeoff” because free cortisol drops from the morning peak until suppertime (B to C) but then rises until bedtime (C to D) and stays relatively high throughout the night. It’s as if a plane landed, taxied, and then took off again too soon.
At the risk of repeating myself, I know I’m pushing things somewhat in this post by introducing all this information. The main things the reader needs to take away at this point are the following:
- Free cortisol rises and falls across 24-hours in a predictable pattern
- Loss of this variation can be a serious problem
- There are key features to the pattern that include an overnight rise in free cortisol and an additional surge in free cortisol after waking
- The profiles need to be interpreted in the light of how the patient feels throughout the day and night. A careful history is important.
- The profiles can provide useful insight and can be indispensable in helping the practitioner to choose the best treatment strategies.
Please tune in for the next post when I’ll discuss treatment and also how the cortisol patterns fit in with other hormones and the health of the liver.
Author: George Gillson, MD, PHD, CCFP
EvolveWell Medical Director
References
Prezio JA, Carreon G, Clerkin E et al. Influence of body composition on adrenal function in obesity. J Clin Endocrinol Metab. 1964 Jun;24:481-5. doi: 10.1210/jcem-24-6-481. PMID: 14187285.
Salehi M, Ferenczi A, Zumoff B. Obesity and cortisol status. Horm Metab Res. 2005 Apr;37(4):193-7. doi: 10.1055/s-2005-861374. PMID: 15952076