24-Hour Urine Testing for Hormones: Rational Wellness Podcast 85
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Dr. Frank Nordt discusses 24 Hour Urine Testing for Hormones with Dr. Ben Weitz.
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1:07 My goal for this podcast is to gain some insights in what we can learn from 24 hour urine hormone testing that can help guide patients to feel better and be healthier. Hormones can be testing using serum, urine, saliva, blood spot, or dried urine. Serum testing is the most common method since it’s easy and is usually covered by insurance. But urine testing also allows you to be able to test not only hormones but their metabolites, which can be helpful, esp. with estrogen metabolism. Dr. David Zava from ZRT Labs has argued that the best way to monitor hormones administered topically is to use saliva testing. And the dried urine testing from DUTCH has recently become one of the more popular methods with the Functional Medicine community.
6:00 Dr. Frank Nordt, the CEO and director of Rhein Labs explained that there are various methods of hormone testing today, including blood, blood spot, 24 hour urine, and dried urine testing. With regard to dried urine testing, while it is convenient to do, since all you have to do is urinate on a piece of filter paper and send it in the envelope, but there is not one published study that supports the validity of dried urine spots. Therefore, according to Dr. Nordt, it is junk science.
7:28 Let’s start by talking about 24 hour urine testing for hormones. It provides insight into the metabolism and turnover of hormones in the body. Dr. Nordt believes it provides the best measure of hormone levels in the tissues. You cannot directly assess hormones in the tissues without taking a biopsy, but that can’t be done on an outpatient basis. So while urine is measuring the levels of hormones that have been excreted versus serum which is measuring hormones in the blood, the key is to find out what levels are in the target tissues of the body.
9:12 Dr. Nordt divides the Rhein Labs 24 hour urine hormone report into estrogens, androgens, and corticosteroids. Estrone (E1) is the storage form of estradiol (E2) and the Estrone:Estradiol ratio should be 2:1, though in the case of estrogen dominance, this can be 4:1. The reference ranges that are reported are divided by decade and include plus or minus one standard deviation from the mean. Some doctors like to look at an ideal reference range, though they may have different ideas what this is. Some feel ideal is what a woman’s levels are in their 20s and other feel it is what hormone levels a woman in her 30s would have.
15:10 When we look at the estrogen metabolites, it appeared a number of years ago from the literature that an increased amount of the 16 hyroxyestrone and looking at the 2:16 ratio would indicate a higher risk of breast cancer. But the more recent research has not really panned out. With respect to oncogenesis, the 4-hydroxyestrone appears to be the better indicator of higher risk than the 16. If the 2 hyroxyestrone is especially high and the 2 methoxyestrone is unusually low, then the person is not methylating properly.
24:02 When we look at testosterone and the other androgens, we can see what is up and down regulated. For example, in men, 5-alpha-reductase upregulation leads to an increase in DHT levels. Or 5-alpha-reductase can be downregulated by drugs like Finasteride, which completely knocks out the 5-alpha-reductase and this can lead to impaired sexual function. If a patient is taking DHEA we can see if it is converted into androstendione and it can then be converted into testosterone or into estrone. For men, DHEA typically does not raise testosterone levels to any substantial level, though it can do this in women.
39:21 Progesterone cannot be measured directly in urine, but we measure the metabolite, pregnanediol, which is a very sensitive indicator for progesterone.
40:14 Dr. Nordt explained that when you measure hormones with either saliva or blood spots, you are only measuring hormones at one spot in time, when hormones are produced in a pulsatile fashion. What if you measure testosterone in the morning and it is normal in the morning but it is low later in the day? You will miss that. One of the problems with saliva testing is that many people have buccal microbleeds, or bleeding from the gums, which will contaminate the samples. Another problem is that saliva testing uses immunologically based assays and these antibodies can have cross-reactivity, which can alter the results. Also, as we age, we have less saliva, so salivary testing gets more difficult to do. If you have difficulty generating enough saliva, then this can create stress and raise cortisol levels.
46:12 Dr. Nordt talked about some of the issues with blood spot testing for hormones, where you prick your finger and drip some blood onto a piece of cardboard. In such a situation, blood often gets contaminated with interstitial fluid and therefore the results are not as reproducible. With respect to the dried urine testing, the results collected at different times during the day are normalized by using an algorithm an algorithm should have no place in a clinical lab. All the results are normalized to creatinine, but to accurately measure creatinine, you need a 24 hour collection. Dr. Nordt’s 24 hour urine collection testing is not available for direct testing to patients but must be ordered by a clinician. Rhein Labs can be contacted through their web site, RheinLabs.com or by calling 503-292-1988.
Dr. Frank Nordt has a PhD chemistry and is the CEO and the Laboratory Director of Rhein Consulting Labs, which offers quality 24 hour urine testing for hormones for both men and women and you can call 503-292-1988.
Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.
Dr. Weitz: This is Dr. Ben Weitz with the Rational Wellness podcast, bringing you the cutting-edge information on health and nutrition from the latest scientific research and by interviewing the top experts in the field. Please subscribe to the Rational Wellness podcast on iTunes and YouTube and sign up for my free ebook on my website by going to drweitz.com. Let’s get started on your road to better health. Hello, Rational Wellness podcasters. Thank you so much for joining me again today. For those of you who enjoy listening to the Rational Wellness podcast, please go to iTunes and give us a ratings and reviews so more people can find out about the Rational Wellness podcast. Today, our topic is to look into 24-hour urine testing for hormones and what we can learn from looking, not only at hormone level but at the hormone metabolites that are also excreted in the urine. My goal for this podcast is to gain some insights in what we can learn from this type of hormone testing that can help guide patients to feel better and be healthier.
To analyze our hormones like estrogen, progesterone, and testosterone, there are various testing methods available today, serum, urine, saliva, blood spot, and dried urine. Serum hormone testing is the most commonly employed method by doctors in the US, especially conventional MDs. It’s certainly the easiest testing requiring only a blood draw on the part of the patients and it’s often the cheapest since it is more likely to be covered by insurance. Many Functional Medicine doctors like urine testing since it allows the measurement of the metabolites of estrogen, which are important for assessing the risks for breast and other estrogen-related cancers. On the other hand, urine testing is not directly measuring hormone levels in the bloodstream or in the tissues, but instead, is measuring hormones and metabolites that have been excreted.
Besides serum and 24-hour urine collection for hormones, there is also saliva, blood spot, and dried urine testing. David Zava from ZRT Labs has published a number of widely read articles that have been published in the Townsend Letter. And he argues that serum, urine, and saliva can all reliably measure our natural hormones, though there is a difference when measuring hormones that patients are taking. He argues that saliva is the best way to monitor hormones that have been administered topically. I’ve read articles by and spoken to other prominent functional medicine doctors who’ve told me that saliva is very unreliable. I also know there are very successful clinicians who use serum, urine, and saliva. They all use different methods, and they all claim to get good results.
The newest method is to use dried urine testing, which is quite popular now with the Functional Medicine community. And it was the most popular form of hormone testing in an informal poll that I gave to 1,300 Functional Medicine practitioners on our closed Facebook page.
So what is the most effective method for testing hormones, both for looking at natural hormones, and to monitor hormones that patients are taking? To sort out this controversy, I’ve asked Dr. Frank Nordt, the president and lab director of Rhein Consulting Laboratories in Portland, Oregon to join us. Dr. Nordt has a PhD in biochemistry and he’s published extensively on hormone testing methodologies. Rhein Labs is a small boutique lab that was the first to develop a reproducible, accurate, and clinically relevant hormone profile for both men and women in 24-hour urine, long before the entry of Genova and others into this arena. Dr. Nordt, thank you for joining us today. And can you tell us about your background and how you came to start Rhein Consulting Labs?
Dr. Nordt: Yes. First of all, I appreciate the opportunity to speak with you and your audience today and I hope to clear up a few or throw some fire on, some controversies that have arisen over the years. My background, as you said, I received a PhD in biochemistry and biophysics at the Oregon Health Sciences University, after which I did a postdoc at the Max Planck Institute in Munich. I went on into industry and worked in pre-clinical research. I was primarily interested in blood flow properties and I worked in the area of stroke. I came back to academia at the medical school and worked in neurology. And to be quite frank, no pun intended, I got sick and tired of academic politics and decided that my skills and interests were in the private sector. And I like to innovate. I continue to collaborate with academia and continue to publish. I’ve been doing this since 1991, and I’ve been doing hormone testing since then using various modalities, primarily serum and then the 24-hour urines.
You’re right, there are various matrices, blood, venous blood, blood spots, 24-hour urine, and as you said, the dried urine testing, which has gained popularity in the last five years or so. I will be quite direct with regard to the dried urine testing. It is convenient, certainly. All one has to do is urinate on a piece of filter paper, basically, and send it in in an envelope and hopefully, get results that are meaningful. I can tell you that there is not one published study that supports the validity of dried urine spots. I have been asked by people to collaborate in regard to this, but I won’t because, quite frankly, it is junk science and I will stand by that. And I will elaborate on that a little bit later.
So why don’t we, first of all, talk a little bit about the 24-hour urines and then I will go into what I think of the other modalities, including blood. As you say, it’s convenient. It’s the most widely used. But let’s go and first look at what I think a profile should look like. And a profile is not just a “panel”, but it’s a well thought out, I think, profile, which, again, provides insight into the metabolism and turnover of the hormones in the body. You mentioned that it’s what is excreted, you’re absolutely right. It is excreted, but I think it provides the best measure of hormones and hormone levels in the tissues. You can’t directly assess hormones in the tissues without taking a biopsy. There have been studies that have actually done that, looked at, for example, breast biopsies, looked at local concentrations of estrogens, androgens, et cetera. But, obviously, that’s not an approach that can be used on an outpatient basis.
Let me throw up a … Can you see that?
Dr. Weitz: Yeah, we can see that.
Dr. Nordt: Okay. First of all, I divide the report into estrogens, androgens, and corticosteroids. On the following page, this is an example of a graphic format. Some people like it, some people don’t. Patients tend to like it because it’s colorful. Frankly, for me, it’s attractive, but not that easy to look at. So mostly what we do is we stick to our old format. This is kind of difficult because I can’t see the sharing. Oh, here it is. I’m sorry. I found it. I’m working with more than one monitor here. So anyway, here we go. So what I want to do is go through what I call the tabular format. These are the same results and as I said, we have estrogens, androgens, and corticosteroids. Starting with the estrogens, we look at estrone. This is an example of a premenopausal patient that is menstruating regularly, and it’s an example of a typical, let’s say 30 to 40 year old. We have all of our reference ranges divided into age by decade. So from 30 to 39, 40, to 49, et cetera. So this is a typical reference range for a 38-year-old in this case, and we see her estrone at 9, estradiol is about half of that.
The importance of looking at ratios, the estrone is the storage form for estradiol and there is an equilibrium between estrone and estradiol. And in aberrant cases, the estrone, for example, in estrogen dominant women, the ratio of estrone to estradiol will be much higher. And we look at that, for example, down here, what I call the potent estrogen ratio, which varies between approximately one and four. Ideally, that ratio is around two. In the graphic format, we have what I call ideal reference ranges. I’m not exactly sure what ideal means, but a lot of the functional medicine people would like to see something idea, an ideal reference range where, for example, a 20 to 30 would be … Some people think we should adjust hormones in postmenopausal women to what they were for a woman in their 20s, some people feel it in their 30s.
As I say, I’m not exactly sure what people mean by an ideal reference range. What we’ve done is taken it from, basically, plus or minus two standard deviations of the mean. We’ve taken it down to plus or minus one standard deviation approximately. What ideal is, is oftentimes in the eyes of the beholder.
Dr. Weitz: I think it’s common in the Functional Medicine world for there to be labs to have normal ranges. And we often consider normal meaning like for example, you measure vitamin D and if it’s above 30, that’s considered normal. But most people in the Functional Medicine community feel that, based on the research, you have the least risk of chronic diseases if you get that level up between 50 and 70. So that’s what we consider an ideal range versus a normal range from a lab.
Dr. Nordt: Right. Now, the problem with hormones is that the research in terms of what is ideal is lacking. And I think there is also a lot of misinformation out there regarding how one should, for example, adjust the postmenopausal woman. As I say, some people think it should be where hormones were in their 20s to 30, others 30s to 40s. Other people feel that, and this is quite controversial and I don’t agree with it. There are what I call high estrogen protocols where women who are postmenopausal actually start menstruating again.
Dr. Weitz: Yeah, that’s because they cycle the progesterone for two week periods to sort of duplicate.
Dr. Nordt: Correct.
Dr. Weitz: Basically, the idea is, or the theory is, that you’re duplicating the hormone levels and the sequence of a woman in her 20s.
Dr. Nordt: Exactly. Again, it’s in the eyes of the physician what they feel is ideal for their patients. As a laboratory, quite frankly, I don’t think it’s my place to prescribe what various practitioners should do.
Dr. Weitz: So let’s go into some of these estrogen metabolites like the 2-hyroxyestrone, the 16-hydroxyestrone, and the 4-hydroxyestrone.
Dr. Nordt: Right. Now, let’s, first of all, talk about the two. Normal metabolism of, for example, estrone, and we use the metabolites of estrone because it is the most abundant if you will estrogen that is active. In other words, the two active ones are estrone and estradiol. There’s more estrone, so we use the metabolites of estrone because the fidelity of the measurement is better than it would be with estradiol. The estradiol actually mimics the estrone, so I’ve never found much point, and we’ve done some work in this regard, I’ve never put a lot of emphasis on measuring the metabolites of estradiol because they, basically, mimic those of estrone. Having said that, there has been controversy about the two to sixteen ratio. Some people continue to feel that it’s a valid marker for-
Dr. Weitz: Breast cancer.
Dr. Nordt: And frankly, a review of the literature would indicate that it isn’t what it was cracked up to be. We continue providing those levels for those people who continue to feel that it is important. And there are people and there is literature that would indicate that it is, so what we do is we provide the information and let the practitioner deem and interpret it how they wish to. I think in terms of oncogenesis, a more current hypothesis revolves around the metabolite that are what we call depurinating adducts leading to apurinic sites leading to errors in DNA repair and mutations and then leading to breast, and in males prostate cancer. Also, the role of catechol estrogens, the estrogen quinones, specifically the oxidation, unfortunately. And catechol estrogen quinones, the oxidation of 4-hydroxyestrone, they act as carcinogens that damage DNA leading to again, cancers of the breast and prostate.
Dr. Weitz: So what you’re saying is that the 4-hydroxyestrone may be a better measure of potential breast cancer risk than the 2:16 ratio.
Dr. Nordt: Correct. And then, following from there is the final metabolism, the hydroxyestrones, it leads to the methoxyestrones, namely 2-methoxy and 4-methoxyestrone. We can get an idea of the efficacy of methylation by looking at those levels. Now, the 4-catechol estrogens in animal models are carcinogenic. The two 2-catechol estrogens are not. There haven’t really been any studies that I’m aware of in humans, but again, like I say, the hypothesis is that it’s the 4-hydroxy and 4-methoxy, if the individual is methylating that those are the “carcinogenic” if you will, estrogens.
Dr. Weitz: Yeah, I interviewed Dr. Lindsey Berkson, and she actually takes the 2-methoxyestrone and she had a whole series of cancers prior to doing this. And she feels that is really significant in helping reduce cancer in her body and I know she was working on possibly trying to get that approved for use.
Dr. Nordt: Yeah. Again I think the evidence is sketchy. I think that we have hints as to what is going on. And to be at the forefront, I think it’s important to measure these and if they are way out of range, if the person is not methylating by, for example, looking at the relationship between the estrone and the 2-hydroxy and 2-methoxyestrones, if the 2-hydroxyestrones are inordinately high and the 2-methoxyestrone is inordinately low, that is an indication that the person is not methylating. I will tell you that the 4-2-methoxy and the 4-hydroxyestrones are relatively low in most individuals. And in most cases, you cannot detect with any degree of certainty that the levels of 4-methoxyestrone in urine. They will be, quite frankly, mostly on the low side and we take the 2-hydroxyestrone and the 2-methoxyestrone to be the indicator of methylation.
Dr. Weitz: By the way, I wanted to mention to the listeners that if you’re listening to this on your phone or in your car, if you want to see the slides that Dr. Nordt is putting up, go to the YouTube page, the Weitz Chiro YouTube page and the video version of the podcast will be there.
Dr. Nordt: Good.
Dr. Weitz: I noticed that you have a separate reference range for women who are taking hormone replacement.
Dr. Nordt: Correct. Because we divide the reference ranges for the estrogens by decade, women who are on hormone replacement are going to have somewhat different levels of estrogens. And most practitioners feel that they do not have to replace the estrogens to the levels of premenopausal women, but should replace them to the point where the patient has no symptoms. And those reference ranges tend to be lower. And again, we provide those reference ranges and they’re taken, basically, from a cohort of patients who are on hormone replacement.
Dr. Weitz: Would it matter what for of estrogen that they’re taking though?
Dr. Nordt: Most people these days are on topical estrogens. If they are on oral estrogens, which I think most people have gotten away from because of the significant first pass effect which occurs. These estrogen levels are primarily from topicals whether they be topical creams or, for example, the patch. I will tell you that with the patch, you can get away with lower doses of estrogen using the patch because it tends to be more efficacious in getting through the skin and into the circulation. And we find that with these lower levels, patients will be without climacteric symptoms. We look at the androgens also and the androgen metabolites of testosterone. There are many women who are on testosterone replacement. The does there generally vary between one and four milligrams per day. Generally, you can get away with one to two milligrams and get adequate levels. The metabolites become important, and I should point this out, metabolites become important in looking at the … Let me bring up another slide here.
Dr. Weitz: Well, right now you’re talking about the metabolites of testosterone, which, if we’re not doing 24-hour urine or dried urine, we are not testing. So what are some of the benefits of looking at these? What can these tell us?
Dr. Nordt: These tell us, I think, if you can see, this is a flow chart. What we can look at and infer are the enzymatic activities which lead to these metabolites, and what is up and downregulated. As an example, 5-alpha-reductase metabolism in women is less important than in men. In men, 5-alpha-reductase upregulation leads to increase in DHT. And the downregulation of 5-alpha-reductase, for example, by drugs such as Finasteride, which completely knocks out the 5-alpha-reductase. And in some men, it cannot recover, which is referred to as the Finasteride syndrome. Oftentimes, these people will probably never have prostate cancer, but sexual function is impaired. Finasteride, the commercial name, if it’s for BPH is Proscar. If it’s for hair growth for the follicularly impaired, it’s known as-
Dr. Weitz: I see that you’re scratching your bald head there Dr. Nordt, for those who are listening and not watching.
Dr. Nordt: Yeah. I’m a little follicularly impaired, yes. In any case, even at low doses of Finasteride, which is, as I said, known as Propecia commercially, it does lead to knocking out, basically, the 5-alpha-reductase. We can look at other enzyme systems. I’ll go back to the profile and-
Dr. Weitz: Yeah, so what do we learn out of looking at these metabolites? So we’ve got the DHT and so the benefit there is we can look at that for prostate health and hair loss. Right?
Dr. Nordt: Correct.
Dr. Weitz: What do we get out of these other metabolites? What can they tell us?
Dr. Nordt: Well, we’ve gone a little bit through the estrogens as far as looking at the various estrogen metabolites and the risk in breast cancer, et cetera. With the androgens, primarily, for example, taking DHEA, DHEA is preferentially metabolized to the other 5-beta-reductase to etiocholanolone down here. Again, the relationship between androsterone and etiocholanolone is 5-alpha and 5-beta-reductase. When we go to the corticosteroids, these metabolites … The corticosteroids starting here with cortisone, again we have the THF and 5-allo-THF, 5-alpha and 5-beta-reductase. But then there’s also an equilibrium between cortisol and cortisone, which is a 17-beta-hydroxysteroid dehydrogenase. And there are two forms of this enzyme.
Dr. Weitz: Hang on one second, Doc. Let’s just finish with the testosterone stuff. So you mentioned DHEA, which converts into androstenedione into testosterone and then into etiocholanolone.
Dr. Nordt: Etiocholanolone and-
Dr. Weitz: What’s the benefit of looking at that? What does that tell us?
Dr. Nordt: Okay. Androsterone, for example, has androgenic activity, whereas the etiocholanolone does not.
Dr. Weitz: Okay.
Dr. Nordt: Eating a lot of DHEA, for example, you can see, by looking at a profile, you can see if there is significant conversion of DHEA into estrogen. These are things that you’re not going to gather from any kind of blood test. You’re not going to be able to see that in any kind of saliva testing because they do not measure the metabolites.
Dr. Weitz: I got it. So you have a patient, they’re low in testosterone and they’re low in DHEA, and you give them supplements of DHEA hoping that’ll boost their testosterone levels, but it may get pushed over into forming more estrogen.
Dr. Nordt: Correct. And that’s especially true in men who oftentimes eat DHEA like candy and end up with mild forms of gynecomastia.
Dr. Weitz: What does eating DHEA like candy mean?
Dr. Nordt: What I mean by that is higher than 50 milligrams.
Dr. Weitz: Okay.
Dr. Nordt: We see people taking 25, 50, 100 milligrams of DHEA. In men, you can never eat enough DHEA to raise testosterone levels in a clinically significant way.
Dr. Weitz: Okay, so you’re putting an end to the thought that some clinicians have and patients who are trying to boost their testosterone levels, you’re saying that taking DHEA in no way is going to meaningfully boost testosterone levels.
Dr. Nordt: That’s correct. In women, in some cases, you can because the testosterone levels in women are much lower than in men. You can raise, in some cases, the testosterone levels in women in a clinically significant way.
Dr. Weitz: On the other hand, I have male patients who when we’ve given them a modest dosage DHEA, like 25 or 50 milligrams, notice significant difference in the way they feel in terms of energy levels and things like that.
Dr. Nordt: Correct. But again, if you look at the testosterone levels per se, and I think in some cases when you look at DHEA, DHEA, as you say, there are some physical effects that people tend to feel better. This is true in women also. But you have to watch it in terms of the aromatase activity, which is oftentimes upregulated.
Dr. Weitz: Which would convert it into estrogen instead of testosterone.
Dr. Nordt: Correct. So they may feel a little bit better, but again, looking at their testosterone levels, per se, you’re not going to see an increase as a result of the DHEA. Some people use 7-Keto-DHEA because they feel that it is not converted to estrone and so we measured-
Dr. Weitz: Is that true?
Dr. Nordt: First of all, if you take 7-Keto-DHEA, it is always going to be outside of the “references range”. The supplementation will lead to higher levels than for example what we call here, the 45 micrograms per day. I’ve seen indications that this is probably a misnomer that 7-Keto does not lead to. Although, chemically, it should not revert to DHEA, so I don’t quite see how it ends up as estrone because once the ketone group has been added at the 7 position, it is then oxidized to the hydroxy and I just don’t see a way of it getting back to estrone. I don’t know what your experience is. I just talked to someone who felt that giving 7-Keto has no advantage in terms of they see that estrone levels are increased by giving 7-Keto. I don’t have enough data.
Dr. Weitz: Okay. So let’s move onto the cortisone and cortisol, and maybe you could start by explaining what’s the difference between cortisol and cortisone.
Dr. Nordt: Okay. Just like estrone is the storage form for estradiol, cortisone, in essence, is the storage form for cortisol. There is an equilibrium between cortisol and cortisone. And in cases where cortisol is needed, there is the reverse direction going from cortisone to cortisol. And there are, basically, three metabolites that I look at in terms of corticosteroid metabolism. That’s the THE, which is tetrahydrocortisone, the THF, tetrahydrocortisols.
Dr. Weitz: So what can that tell us, looking at THE?
Dr. Nordt: Okay. There are two things to look at. One is, if the enzyme is upregulated to metabolize cortisol leading to a depletion of cortisol to cortisone, then that cortisone, in order to get rid of it, it is metabolized at the THE.
Dr. Weitz: Okay.
Dr. Nordt: If you look at the sum of the three metabolites, and I think that’s probably the most important thing that we can say, the THE plus THF plus 5-allo-THF, if that is elevated in men greater than about 6,000 to 7,000 micrograms per day, you can almost bet that individual is insulin resistant, has metabolic syndrome, is pre-diabetic, or frankly, diabetic. We have found, I’d say, over a dozen cases where these enzymes with the THE, THF, and 5-allo-THF rise to levels greater than about 15,000, you can almost bet that individual has most likely an adrenal adenoma. And the cortisol levels continued to be normal. What happens is the body compensates for the increases in cortisol by upregulating the enzymes, metabolizing cortisone and cortisol, and until, basically, there is no more headroom and you end up with very high levels of these metabolites.
At which point, when you do run out of headroom, it’s at that point that the cortisol levels actually elevate. And we’ve had, like I say, around a dozen, a little bit more, about fifteen of these kinds of cases where the surgeon then remarked, when imaging these individuals, “How did you ever find this?” These people end up in the physician’s office. They measure 24-hour urinary cortisols and they are perfectly normal. They’re sent home but they know that something is wrong.
So there are two advantages to measuring these metabolites. One is an early warning indicator for insulin resistance. And the second one, like I say, which is relatively rare, but nevertheless, you can catch these adenomas at a very early stage, and at least watch them until they become clinically significant and need to be surgically removed. There are a couple of other metabolites, the 11-beta-OHAN, which is the androsterone. Again, the relationship there is 5-alpha and 5-beta-reductase metabolism. The same kind of thing the corticosterones, THA, THB, and 5-allo-THB. Some people ascribe significance to those in terms of their metabolism toward aldosterone. We have clients that want those. I don’t personally ascribe that much significance to these other than, again, an indicator of 5-alpha and 5-beta-reductase metabolism. But again, like I say, we try to cover the bases if you will.
Dr. Weitz: Okay. That’s good. I don’t want to get too much into the weeds on some of this stuff. We may lose some of the viewers and listeners.
Dr. Nordt: Right. This is the problem and some of this stuff, certainly for lay individuals, gets to be pretty technical. And as you say, especially for lay people, I tend to stay out of the …let me put it this way, over interpretation. I do want to say something about progesterone. Progesterone cannot be measured directly in urine. We use the metabolite, which is pregnanediol. It is a very sensitive indicator for progesterone and there is a lot of fidelity to the measurement. If you’ve ever looked at progesterone in serum, in premenopausal as well as postmenopausal women who are on replacement, serum levels are oftentimes quite low. The reason for that is the progesterone is rapidly compartmentalized taken out of the serum. But if you look at the target tissue and you look at the urine where you actually are looking at turnover, you can get very nice measurements of progesterone.
I do want to say something about both the saliva testing and blood spots, as well as urine spots. The major drawback of any kind of spot testing, in other words, it’s a single point in time. Hormones are produced in a pulsatile fashion. And in serum, for example, testosterone is a good example, testosterone measurements in serum should be taken in the morning. That’s convention. What happens after the morning is oftentimes not looked at at all. And we have lots of indications that testosterone levels may be perfectly normal in the morning, but decrease over the day and become quite low in the afternoon and evening.
The issue there is that if you look at a spot test, whether a blood spot of a saliva test, and I should say that saliva tests for the sex hormones are controversial because of the relatively low levels, and all of the saliva measurements and this is where I think some people find them to be useful. Some people say well, I get different levels all the time testing the same patient. All of the saliva testing is done using immunologically based assays. In other words, they involve using an antibody to the hormone which is being measured. The steroids and again, this gets technical, but the steroids to an antibody tend to look the same. And there is a considerable cross-reactivity. In the case of testosterone in women, for example, using an immunologically based assay, and there’s a serious paper out there, you can guess better than you can measure because the measurements tend to be all over the place.
The other problem with saliva testing, there are two issues. One is buccal microbleeds. The hormone levels in serum or in blood are approximately 1,000 times higher than they are in the saliva. Depending on the oral health of that individual and all of us have buccal microbleeds to one extent or another.
Dr. Weitz: You’re talking about tiny bits of blood in your mouth.
Dr. Nordt: Correct.
Dr. Weitz: From your nose or something like that.
Dr. Nordt: Yeah. From the gums. Some people who have oral health that is somewhat compromised, you crush your teeth and all of a sudden you have some blood on the toothbrush. If you contaminate the saliva, even to a level where you cannot see the blood, that measurement in the saliva will be compromised. The other issue with saliva is the lack thereof. People, as they grow older, the amount of saliva that is secreted decreases significantly depending on stress levels. We’ve all experienced this. So you get a dry mouth syndrome. Dry mouth syndrome is also an issue in people who are on certain medications. Saliva testing becomes really problematic and unless done under very rigorously controlled circumstances, these measurements on an outpatient basis are oftentimes not particularly efficacious.
So to summarize there, a contaminated saliva sample is a compromised sample. If you stimulate saliva flow using chewing on cotton. Some labs have you try to stimulate saliva flow. That also becomes a compromised sample. I work with the primate center here, the Regional Primate Center here in Oregon where cortisol measurements are taken from monkeys in order to evaluate stress levels. They are very, very careful not to stress these monkeys before taking the saliva sample because even the act of collection, and this is true in human also, the act of collection can change the cortisol levels.
Dr. Weitz: But, Doc, living in the modern world, I feel like we’re all a bunch of stressed-out monkeys.
Dr. Nordt: You have a point. Right now, to be honest with you, I’m a little stressed talking about all of this and I have a dry mouth. People who will sit for 30, 45 minutes trying to collect an adequate specimen. It’s problematic.
Dr. Weitz: Hey, let’s go back to full screen view for the last few minutes here.
Dr. Nordt: Are we back?
Dr. Weitz: Yeah, that’s good.
Dr. Nordt: Let me then talk a little bit about blood spots.
Dr. Weitz: Okay.
Dr. Nordt: And I’ve asked this question and I’ve never gotten an adequate answer.
Dr. Weitz: This is where you prick your finger like you would do to check your blood glucose.
Dr. Nordt: Correct.
Dr. Weitz: Some practitioners like this form of testing as do patients because you don’t have to go into a lab to have it done and you can just put the blood on a little piece of cardboard and mail it in.
Dr. Nordt: Correct. I hope and I don’t know how many people in your audience are aware of the Theranos Labs.
Dr. Weitz: Yeah, but I think that’s not really comparable to-
Dr. Nordt: Well, no it’s not.
Dr. Weitz: I mean that was a big scam. They were claiming that they had this machine that you could just put the blood in. Meanwhile, somebody took the blood, brought it in the back, had a bunch of lab technicians using the normal testing everybody else is using and it was just a big show for the investors.
Dr. Nordt: Correct. It goes beyond that. I asked the question what is the difference between a blood spot taken from a finger prick on a piece of filter paper and a blood spot in a nanotainer. The issue here is every time you take a finger prick, that blood is contaminated with interstitial fluid. This goes back to my days in graduate school. Much of my work was done on the red blood cell membrane. If you did a finger prick and you looked at, for example, the surface properties of red cells from a finger prick, they will be different every time, and it’s because of the absorption of proteins from the interstitial fluid. One of the hypotheses of why the nanotainer didn’t work is because of the contamination. And there were some really good editorials in the Wall Street Journal from experts in this field that feel that finger pricks, and I certainly share that, that finger pricks lead to blood samples which cannot be tested adequately and reproducibly. Having said that, blood spots the same problem, you have a point in time. Getting to-
Dr. Weitz: Of course, there could be benefits to having a point in time too. Like, for example, when we do the salivary cortisol testing, we don’t just learn what the total cortisol level is, but we learn is it low or high in the morning as opposed to the evening, if it’s supposed to be higher in the morning and then it’s supposed to drop in the evening. If it’s lower in the morning and then it’s higher in the evening, that interferes with sleep. So there could be benefits to knowing where hormones are at a certain point in time during the day.
Dr. Nordt: Yeah, the issue again gets back to adequate collection of the samples. And we actually did a study in conjunction with the University of Washington, the Fred Hutchinson Cancer Research Institute, on cortisol levels in shift workers. And quite frankly, there are very few people who work a normal shift, in other words, a day shift, who have abnormal cortisol rhythms. They may have low cortisol. You will discover low cortisol and at the 24-hour urinary cortisol is still the gold standard in that regard. If you have low cortisol overall, you will see that in the 24-hour urine. If you have high cortisol levels in the morning, for example, you will see that in the 24-hour urine.
Dr. Weitz: Right.
Dr. Nordt: The rhythm is very rarely an issue per se.
Dr. Weitz: I would say just to give you a little argument, pushback on that. Would say that most of us in the Functional Medicine community, myself included, feel that the majority of our patients are stressed out and we do see that the cortisol tends to be lower in the morning and it’s not unusual to get a spike in the evening when they’re not supposed to.
Dr. Nordt: Yeah. The evening spike, oftentimes, and this I st problem, you don’t really know how to interpret it because you don’t know under what circumstances that sample was collected. Let’s say that individual is, in the evening, they normally don’t collect their saliva in the evening, they sit there, they have a little bit of trouble producing enough saliva. And then, all of a sudden, that cortisol level is artificially increased in the evening. It’s true in some people, not true in others. How do you know when?
Dr. Weitz: You mean they’re so stressed out from having to spit into the tube that their cortisol level goes up?
Dr. Nordt: Absolutely, absolutely. This is exactly what I’m getting at. Not in all cases, but if you don’t know and you see the spike in the evening, is it due to stress.
Dr. Weitz: Well, you know, I would say that I’ve seen enough patients with that sort of effect who report having trouble with sleep. And then we use adaptogenic herbs that help to calm out the adrenal levels and sometimes glandulars. And we often find that those patients feel better. I think that there’s some truth in that.
Dr. Nordt: I think this is really important because, as you mentioned, the urine spots have become very popular.
Dr. Weitz: Yeah.
Dr. Nordt: As I indicated, there is not one publication out there that supports the validity of this type of testing.
Dr. Weitz: Okay.
Dr. Nordt: Number one. Number two, there are different modalities that are being promulgated, but a urine sample collected at 8:00 in the morning is, if you’ve gone to the bathroom at 5:00 in the morning, that 8:00 sample is going to be different if you didn’t urinate at 5:00 in the morning. The attempt is made to normalize these results by using “over several samples throughout the day”, the attempt is made to normalize these results and approximate the total production using an algorithm. An algorithm infers information that isn’t there. And I think an algorithm has no place in a clinical laboratory. If we can measure it, measure it.
And a third issue is that all of the results are normalized to creatinine. The creatinine levels that are reported as being the normal range are in these urine spots differ by a factor of ten. In other words, from low to high is a tenfold difference. In urine, in the 24-hour urine, that factor is roughly four, so it’s twice as much. Why do they have such a broad range for creatinine is to try to get relatively “normal” results. Creatinine varies with age, it varies with diet, it varies on the basis of genetics. Why do we take a 24-hour urinary creatinine level to measure kidney function? We don’t use a spot creatinine. We don’t use a serum creatinine. No, we use a 24-hour urinary creatinine.
Dr. Weitz: Okay. I got it, Doc. Yeah. You made some good points there. So we need to wrap.
Dr. Nordt: Okay.
Dr. Weitz: So why don’t you tell us how we get a hold of your lab testing and how do we sign up as providers? Is it available just through providers? Can patients-
Dr. Nordt: There is a law in the state of Oregon and I agree with it, that it can only be ordered on the basis of a provider.
Dr. Weitz: How do providers sign up?
Dr. Nordt: They give us a call at 503-292-1988. As you mentioned at the beginning, we are a small lab. We specialize in this. We do bill insurance. 24-hour urinary profiles are reimbursable by most insurance companies. We are preferred providers for a number of insurance companies. Even if we are not preferred providers, we oftentimes are successful at getting full, or at least partial reimbursement, usually somewhere around 80%. Our pricing is such that it is the same for all practitioners and patients. We bill insurance companies the same amount that we bill a patient without insurance. In that sense, and we pride ourselves in this, we do have transparent pricing. We don’t, like I say, charge an insurance company a different price than we charge a patient. The pricing is presently $280 for the full profile. I think that’s quite reasonable. I am available to help with interpretation. If you do one, two, or three of these and give me a call, you will become an expert in interpretation. The profile, like I say, is a profile you oftentimes have to take a little bit of a step back and not just look at each individual value, you look at it sort of like an impressionist painting. If you get too close all you see are dots. Step back and you get the complete picture.
Dr. Weitz: Sounds good, Doc. And what’s the website for your company?
Dr. Nordt: Www.rhein labs, that’s spelled R-H-E-I-N, as in November, R-H-E-I-N L-A-B-S.com.
Dr. Weitz: Excellent.
Dr. Nordt: We’re available and if you have more questions, if you want to talk about some of these things a little bit more in terms of the matrices, saliva, blood, whatever, give us a call, I’m available. We do answer our phones and you do get to talk to me also.
Dr. Weitz: Excellent. Thank you so much, Doc.
Dr. Nordt: You’re welcome.
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