Environmental Influences on Thyroid Function: Implications for Human Health
1:00 pm US Eastern Time
Call Transcript
1) Welcome: Elise Miller, MEd, Coordinator, CHE Learning And Developmental Disabilities Initiative, and Executive Director of Institute for Children's Environmental Health
2) First Speaker: Tom Zoeller, PhD, Professor, Biology Department, University of Massachusetts-Amherst
Unfortunately, there was a problem with the recording of this call. Although most of the call was unaffected, the first 5-10 minutes were cut out. Presentation transcripts for the first speaker, Dr. Tom Zoeller, are therefore missing. We hope to provide you with a presentation summary in the next week. For more information on Dr. Zoeller’s work, please visit: http://www.bio.umass.edu/biology/zoeller/.
3) Second Speaker: Kevin Crofton, US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Neurotoxicology Division
The US EPA actually has a mandate under FQPA, which is the Food Quality Protection Act, to use a cumulative risk assessment approach for chemicals that share what is termed a “common mechanism.” From an environmental perspective, a concern with this is that thyroid disruptors – and I use that term very broadly, to mean a chemical which will disrupt the function of the gland, which would include what Tom talked about, in terms of hormone synthesis, transport of the hormones to the cell, use of that hormone in the cell, and even, and most people don’t think very much about this, but the liver. The liver actually plays a large role in catabolism, meaning metabolism or disruption of the hormone. Anything that disrupts any of those processes is what I call a thyroid disruptor.
And there are a number of well-known environmental targets for these. So you can hit, as I’ve said, uptake in the glands; you can hit synthesis in the gland; you can disrupt the transport; as Tom says, there are some direct effects on the receptor that we know about; and we know that a lot of environmental chemicals will up-regulate the process of catabolism. These processes all lead to disruptions in the circulating levels of hormones, with one exception, and that’s the effects that are direct on the receptor, that Tom was talking about. Our goal has been, and the project that we’ve had ongoing for quite a while now, is to better understand the risk of these simultaneous exposures to chemicals, and how they disrupt circulating levels of hormones, where the ultimate goal is protecting against adverse effects on neurodevelopment.
Elise actually said that I should mention a recent study that we published. I’ll spend about a minute describing this, and then tell you a little bit about what happens, or what we found. We used a short-term rodent model to look at the effects of a large mixture of PHAHs. Those are polyhalogenated aromatic hydrocarbons. Those include chemicals like dioxins and dibenzyl furans and PCBs. These are very commonly found in pretty much any environmental media you want to look at, including humans.
We used a short-term rodent model for this, because we’ve shown that these in the past have been a good and sensitive marker for the kinds of mechanisms that these compounds will disrupt. We measured thyroid circulating levels of hormones in these animals. We did extensive characterization of the dose-response curves for 18 PHAHs. That’s kind of important because in the kind of statistical modeling that’s used to analyze this data, the better the dose response function, the better you are able to actually analyze the data. We then actually tested a mixture of these 18 chemicals. The composition of this mixture was based on human exposures. By that, I mean there were very small amounts of dioxin in this mixture, and there were large concentrations of some of the PCBs, like PCB153.
We actually went to sources like human breast milk samples, human fat tissue samples, and samples of beef and fish to find out what the mixture concentration was to try to create a really, truly environmentally relevant mixture. The other thing we did was we actually went down into the low-dose range. We actually tested doses given to the rat, which are roughly equivalent to that of human background exposures.
What did we find? We found that additivity theory actually predicts effects at the low-end of the mixture dose. If you’re using dilutions of that mixture which represent something in the neighborhood of where humans are getting exposed, that additivity theory – the statistics behind that – will actually predict those effects. We also found a small amount of synergy at the high end. So if you’re talking about doses which are orders of magnitude higher than what humans would get exposed to, then additivity theory actually under-predicts risk there, but not by very much. We’re within about a 2-fold range of predicting, which is pretty good.
I also wanted to outline a little bit of some of the uncertainties in this work to make sure that people don’t make too much of this. We only tested one of the sort of tox-pathways. When I talked earlier about the different target sites that can be disrupted, the only one that these chemicals really aim at primarily, is up-regulating liver catabolism. Tom and some others have some evidence that there may be a small number of direct effects at the receptor covering two pathways. There was also only short-term dosing. We used rats. Everybody, I think, on the phone is pretty well aware of the uncertainties that happen when you try and take rat data and extrapolate it to human.
Then one of the other things that’s really important is one of the pathways that we looked at – it’s the molecular target for these chemicals that causes the up-regulation of enzymes in the liver which then causes a decrease in the circulating hormone level. It’s called the CAR PXR pathway. Without getting too in-depth on it, there is a little bit of in-vitro evidence which would suggest that some environmental chemicals which act as agonists at that pathway, actually act as antagonists at that pathway in human tissue. That’s in-vitro evidence, and it’s something that we’re trying to follow up. I just wanted to make sure people understood that the sky’s not falling, based on this work. But it does suggest that we need to do a lot more work in this area.
Elise Miller: Thank you so much, Kevin. It’s so important that we begin to do this kind of additive and synergistic research. As you’ve stated, it’s been very rare. Thank you for your work in that arena.
4) Third Speaker: James Haddow, MD, Professor and Division Director, Department of Pathology, Division of Medical Screening Women and Infants Hospital of Rhode Island
The work that I’m going to talk about that we have done, focuses on a different area in that we really weren’t able to examine some of the basics that have just been discussed; namely, some of the environmental antecedents of thyroid deficiency. What we did do was look at a general population of women who had been pregnant. We had an opportunity to do some routine testing on them. Then we were able to go back 7-9 years later, and examine their children – and also, to follow the women up – to see how they were doing, as far as their thyroid function was concerned.
We had discovered that the children of women who were thyroid-deficient but not diagnosed as being thyroid-deficient - in other words, they couldn’t be treated during pregnancy - had IQs that averaged 7 points lower than control children. We were able to do this study because we had serum from 25,000 pregnancies that had been tested in our laboratories. We were able to do the thyroid testing – specifically the TSH or thyroid-stimulating hormone testing – 7 years after the pregnancy, determine which of the measurements were consistent with thyroid deficiency, then, to set up a case-control study, in which we went out and found the women and asked them to come with their children, so that we could do the appropriate testing.
The first finding was, as I’d mentioned, that the IQs averaged 7 points lower on the children whose mothers had been untreated and thyroid-deficient during pregnancy. The second finding, which I think would be relevant to this call, was that when we inquired of the women what their current status was, as far as they knew, as far as thyroid was concerned, we discovered that 2/3 of the women who were thyroid-deficient but not treated during pregnancy now were permanently hypothyroid. We were able to extract the same information from our controls. And we learned that about 4 percent of those were now thyroid-deficient. That’s consistent with reports from other long-range follow-up studies.
The presence of thyroid deficiency, as measured by TSH in pregnancy, turns out to be a strong marker for permanent hypothyroidism in the years that follow the pregnancy. Furthermore, we discovered that it took an average of 5 years for the diagnosis to be made clinically. And about 4 or 5 of the women had not been diagnosed until we actually helped make the diagnosis, 7 or 8 years later. This, to us, was a revelation. We actually didn’t anticipate that this large a percentage of women would actually turn out to be permanently hypothyroid. This led us to begin designing further studies, to try to learn more about how to deal with this, and how to avoid some of the adverse consequences that might occur if the women were not diagnosed. I think that’s pretty much the summary of the relevant information.
Elise Miller: Excellent. Thank you so much, Dr. Haddow. Finally, Dr. Gregory Brent will focus on the implications of public policy on some of the research and thyroid screenings and testing that have been described.
5) Fourth Speaker: Gregory A. Brent, MD, Professor of Medicine and Physiology, David Geffen School of Medicine at UCLA, and Chief, Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System
It’s a pleasure to be on the call today. I really come at this from a couple points of view: one, as a basic researcher in iodine-transport and thyroid hormone action; but also, in my role as Secretary of the American Thyroid Association. I’ve been involved in the last several years with trying to translate some of this information you’ve heard about into public policy, and trying to impact things.
Just to pick up on what Jim talked about, his studies have just a huge impact on the area. Not only to look at identifying women who are hypothyroid and the impact on the intellectual development of their offspring, but just understanding that pregnant women and their fetuses are a marker of susceptibility to reduced thyroid function, and agents that might do that – some of which you heard about, before.
So I’ve had a lot of interest in looking at that. Some examples of that would be iodine nutrition, which in some areas of the US may not be adequate, and this would be a target for intervention, in terms of iodine supplementation during pregnancy. Some very recent information is showing that women with this mild sort of hypothyroidism that Dr. Haddow talked about may also be at major risk for preterm delivery. Of course, there are lots of impacts of preterm delivery, in terms of intellectual development and neurological development.
At the public policy level, we’re really trying to get all the people that are involved in identification and study of these diseases as well as treatment, together. From the medical point of view, we’re trying to especially enlist the cooperation of OB-GYNs who see many of these pregnant women, as well as pediatricians. And also, to expand the information that you’ve heard about from people that are doing the basic research - toxicologists, epidemiologists.
Actually, just to call your attention to some of the materials that are in the resource section on this – there have been efforts of working with the National Institute of Environmental Health with the CDC, to try to identify what the issues are. There are proceedings from some of these conferences that are posted for you, as well as efforts we have of the upcoming conference on March 24th, 2006, that will bring these people together, to expand not only looking at environmental impacts on thyroid hormone action, as you’ve heard about in synthesis, but even looking at some of the increased incidence of thyroid diseases, such as thyroid cancer, which seems to be on the increase, autoimmune thyroid disease, and what potential environmental triggers there could be for that.
The goal in this area is to both identify the diseases and what the connections are, as well as to look at some ways to intervene. The key, really, to those interventions are cooperating across disciplines and across agencies. You can see some examples of that stored in the “Resource,” section. I look forward to the questions and discussion.
Elise Miller: Great. Thank you so much to all four of you for being so clear and succinct. Probably one of the best modeling of that, that we’ve had on these calls. Thank you very much. I’m sure you’ve also provoked a number of questions in peoples’ minds. I think we’ll now open it up to q-and-a. We have about a half hour, or so.
6) Questions / Comments/ Discussion
Dr. Philip R. Lee: This is Phil Lee. I’d like to ask Brent a question about the policy. To what extent have you involved organizations like Kaiser Permanente or other organizations with large numbers of pregnant women, where you might effect studies of those populations on a fairly systematic basis?
Dr. Gregory A. Brent: Yes. That’s a great question I’m sure that Dr. Haddow will have more. He’s really done the epidemiology for those large studies on pregnancy. I’ll make a quick comment, and then let him comment on the question, too. I think that what you’re asking is, how do we translate some of the information to the large groups, both to effect change and how they practice clinically, as well as to use the information from those large groups? I guess the answer, from our point of view, is that we’re working on a number of levels, especially, to impact OB-GYN behavior. We’re working with international organizations.
Part of the problem is knowing exactly what to instruct - we know that there are women who are hypothyroid and pregnant who are not being identified - and what the best ways are to screen those women, and how to identify them. That’s certainly it. I’m going to turn it to Dr. Haddow, because I know that he’ll have some comments on that question.
Dr. James Haddow: I think the policy is still in the shaping stage for how to deal with this situation of thyroid-deficiency in pregnancy. All the way from trying to make sure that the laboratory performance is correct because there are some variations in the way that these tests are measured in the TSH levels during pregnancy, from non-pregnancy.
Beyond that there’s a question, and I think it’s certainly a correct question that’s been raised, that we don’t know yet if we can avoid the IQ problems by identification and treatment of the women during pregnancy. We can correct the problem in the mother, but whether or not the brain problem has already occurred is not yet clear. That’s a matter that I think several groups have been trying to figure out a way to study.
When it comes to the long-term consequences to the mother, I think that those are less an issue. In other words, we know – we’ve documented – that women with thyroid-deficiency, most of them will go on to become truly hypothyroid. This is not just from our study, but from a study in England as well. I don’t think that that’s such a problem. Although, I do feel from having looked at the literature recently, that we could gain by having more specific information about where the cut-off is for risk of going into the state of permanent hypothyroidism. How thyroid-deficient do you need to be, in order to be at high risk? These are more questions of refinement than they are the primary issue of the fact that there is this risk, at least in a select group of women who are thyroid-deficient during pregnancy.
In any case, the one area that you might be interested in is that we surveyed all major practices in the State of Maine, late in 2004, and it’s just coming out into publication in the next couple of months. It was to see what proportion of physicians were screening routinely. It turned out that in Maine, about 2/3 were screening – either routinely or close-enough to routinely – that it could be considered in that category. As a word of caution, that is probably unusual, in that the original studies that I quoted were done in Maine. The physicians in Maine were sensitized to this. I think that many of them simply picked up on the fact that even in their own state, we have this finding that occurred from our study.
The short answer is that we’re still – I think – in a state of flux about establishing a permanent policy. As with any of these matters in medicine, it really does take time, and a lot of working through. I think that Gregory and the ATA are pursuing a steady course, trying to help everyone understand what direction might make sense. There are other groups, as well, involved. There are some variations in the ways they view policymaking, right now. I think we’ll see a clearer story emerge over the next 2 or 3 years.
Elise Miller: Thank you. I just want to remind participants that Dr. Phil Lee is Chair of the Collaborative. We really appreciate that excellent question and the very helpful responses. Other questions, please?
Donna Barnett: Yes. My name’s Donna Barnett. I’m an individual that was interested in a conference call because I had thyroid cancer. I was diagnosed in 1984, when I was 24. There’s been no history of cancer in my family. I’m dependent upon Synthroid right now. There’s been talk that Synthroid’s has had some problems. But it’s the only thing I’ve known. I was wondering if you could speak to the effectiveness of Synthroid or other hormone replacements, and what hormone disruptors I may be aware of or should be aware of.
Dr. Tom Zoeller: Yes. This is Dr. Zoeller. Greg Brent probably has a much better sense, since he is the clinician that prescribes thyroid hormone. He can give you a sense of the different activities of the preparations. At least I hope that’s right, Greg.
Dr. Gregory Brent: Yes. That’s fine. Maybe I could make a comment and maybe turn it back to you, Tom. I guess the question is, well there are a couple there. When you take the synthetic thyroid hormone, it is chemically identical to what your thyroid makes, in terms of the composition T4. But it would be equally affected if there are the kind of disruptors that Dr. Zoeller and Dr. Crofton talked about, relative to the thyroid-hormone action. So that would be independent of the preparation you’re taking.
There is some interest in the thyroid-hormone field, in terms of the mode of replacement, whether you only use levathyroxine – so-called T4 – or add, additionally, the activated form T3. It may be that some of these environmental toxicants that we’re talking about, in fact, Dr. Crofton mentioned this, that may be acting in the liver that would effect thyroid-hormone metabolism. If one were especially exposed to those, or sensitive to them, it may be that you’d have a different mode of replacement. Like some of the other things we’re talking about, this is an area where – based on animal models – it may be the reality is tough in an individual patient, to do the kind of tests, to understand how thyroid-hormone is acting in these tissues. But there’s a lot of interest to do that.
The other issue that you’ve mentioned, in terms of thyroid cancer – the best model is in Chernobyl. Clearly, radiation exposure has increased thyroid cancer. The incidence of thyroid cancer in women in the US is going up. We’re actively trying to look at areas. There are investigators at the National Cancer Institute, trying to identify what those factors are that are promoting it. So there are kind of 2 parts to the question.
Dr. Tom Zoeller: The only thing I might add to that is that there are a number of studies that are trying to associate body burdens of a variety of factors. Like polychlorinated biphenyls and Polybrominated Diphenyl Ethers with thyroid function. While some of these studies have seen an association – that is the higher the level of PCB body burden, for example – the lower your thyroid-hormone levels would be.
Still, those thyroid-hormone levels are within the normal range for the population. So at this point, it’s not really clear to what extent environmental chemicals are impacting human thyroid function. That’s a difficult issue. I’m, for one, not convinced that there isn’t an association because I don’t think the kinds of studies that need to be done have been done. Those are the kinds of chemicals that you would worry about.
Donna Barnett: I just want to mention that in the early 1980s, I lived with my boyfriend who I slept with every night, who was working on the nuclear power plants in Orange County. I don’t know if he brought anything home. I don’t know if other people in that area have a higher incidence of cancer.
Dr. Tom Zoeller: That’s a good point.
Dr. Ernest Sternglass: I’m Professor Emeritus at the University of Pittsburgh Department of Radiology. I have been investigating the role of very low levels of radioactivity from nuclear plants, and from dental radiography. I wondered whether or not Dr. Brent might want to comment on the article by Dr. Hujoel and others in the April 28th JAMA on Ante Partum dental radiography, and infant low-birth weight, which clearly indicates that very small doses - such as we get from x-rays, dental x-rays – to the thyroid, and from environmental small concentrations of releases from nuclear plants, could be a significant synergistic factor in the rise of hypothyroidism and cancer.
Dr. Tom Zoeller: I’m not familiar with the article. Though I certainly would echo that there’s a lot of interest in what you’re describing. There’s a recent article in The Scientist on just tracking from the nuclear fallout in previous nuclear testings – trying to track effects on thyroid function. This is significant, I know. When I go to the dentist and get x-rays, I’m sure that my thyroid is covered. Maybe Dr. Haddow or the other panelists have more knowledge on this.
Elise Miller: Other comments?
Dr. James Haddow: The one thing, though, I would say – which we should be a bit cautious about – is that making the connection between the dental radiography, thyroid and low birth weight – I think is something that we have to be very careful about. Although I haven’t looked at the stories directly of dental x-ray, the association between thyroid deficiency and low birth weight is weak. It’s there, but it’s not a strong association. I think we’d have to really look into it more closely before making any definitive statements, as far as the x-ray factor is concerned.
Dr. Sandra Ross: This is Sandy Ross, at Health & Habitat. I wonder if there’s any information on the incidence of hypothyroidism and fluoride in the drinking water.
Dr. Kevin Crofton: Not that I know of.
Dr. Gregory A. Brent: Yes. I was going to defer to Dr. Crofton, but I was involved with the perchlorate committee on National Academy of Science. I think we looked at every aspect of water related to thyroid function. As far as I know, this did not come up.
Dr. Roy Ozanne: I’m a practicing physician. I’ve been working with – primarily – nutrition, for the last 25 or 30 years. I wonder a little bit about the forest and the trees, here. We see, as time’s going on, as we get increased toxicity, decreased nutrition or whatever it is – both diabetes, adrenals, thyroid, reproductive hormones… We can talk about every single system of our bodies. What I see in patients that really take on a very serious approach to nutrition is, they have fewer of all of these problems. All of their problems get less severe. And their children are markedly better, when we work on their health.
We need all this specific documenting what chemicals do what, but not to lose track in the meanwhile, that one of the best overall protections is an extremely good diet – which is not easy to do these days. Then, I’m wondering. The best nutritional group I’ve found is the Weston Price Foundation. They’re doing an excellent job of promoting high-quality foods. Especially, targeting mothers and pre-conception nutrition. There are quite a large number of people now very motivated in that foundation. It’s a grassroots organization. There might be a large-enough group to get some really good information about how do these different factors change, when there is a very high level of nutrition? It might be a wonderful group to get some more information. It might be very practical and useful, in terms of how do we cope with this increasing burden of toxicity.
Elise Miller: This is a really important question, and we’ve given some thought in the collaborative, in terms of the overlap between toxic chemicals and nutrition. Are there any comments from the panel, or on the nutrition question?
Dr. Kevin Crofton: Yes. One of the things that has worried me, and we are actually beginning a very small research program on, is the potential interface between what I call “marginal iodine deficiencies.” These are people who would not normally be tagged by a physician for having an iodine deficiency, but maybe sort of on the cusp. The interface between that and environmental chemicals that might impact the thyroid-hormone system.
Dr. Roy Ozanne: I might add that it is a good idea to watch the natural iodine, because it is protective against the uptake of small amounts of radioactive iodine. That could be a big factor in the diet, as well as antioxidants that are involved in the protection of the body against free radical damage, which is the dominant damage from low-level ionizing radiation. The last comment on the nutrition: when doing iodine challenge tests, where you measure excretion before you give iodine, give 50 micrograms or whatever that was – level of iodine - then retest. I don’t find a normal person in my practice in terms of iodine sufficiency. I think that’s true - it’s not just iodine that we’re deficient in. Thank you for considering the situation.
Dr. Lynne Cannon: This is Lynne Cannon, from the Learning Disabilities Association. I have a question for Dr. Haddow. I wanted to know, in your group of untreated patients, whether you’ve studied any subsequent pregnancies of those patients, and in fact looked at the younger siblings - the IQ of the younger siblings – of the children that you identified with lower IQs. I wanted to know if there was a further lowering, whether there was no lowering, or whether it was essentially the same as the first child that you were studying.
Dr. James Haddow: We did not look at subsequent children. We weren’t smart enough in our study design to include that. This is one of the things that we regret. We’d love to have had that information. We had a certain resource to work with, and we had to focus on the primary children – the index children.
Tom Muir: This is Tom Muir, retired Environment Canada. This is to Kevin Crofton. Do you have any plans on adding any more chemicals into the mix? Like brominated flame retardants or pthalates or bisphenol A?
Dr. Kevin Crofton: That’s actually a great question. The answer is, “Yes.” Maybe not brominated flame retardants, because we think they act quite similarly to the PCBs. But definitely, to add things like fungicides which act to block synthesis of the hormones. Perchlorate, which will block iodine uptake, and then maybe even add a nutritional component, as I said, by actually doing this in marginally iodine-deficient animals. That’s an excellent question.
Tom Muir: I think I was asking about the brominated flame retardants just to get the dose up, to better reflect the real-world exposures, as you pointed out. Not just the mechanism, but to add something else, making it worse.
Dr. Kevin Crofton: Oh, I see. I hadn’t thought of it that way. That’s a very interesting comment. Depending upon the population you’re looking at, you could actually almost double the entire PHAH load.
Elise Miller: Other questions, please.
Dr. Phyllis Mullinex: I might make one comment. It was mentioned earlier – a question about fluoride. There are some new studies out that are coming from countries that have fluoride-poisoning problems in the drinking water. Usually higher than what we have, here. Nonetheless, there are several research papers that have looked at the iodine levels in conjunction with fluoride levels, and found that there was an additive and synergistic effect between fluoride and iodine levels. These papers have shown where they’re looking not only at the PSH level, but they’re also looking at fluoride-receptor effects and effects on other enzymes, and synthesis-and-release. I just wondered if there was any comment, if you’ve been following any of that new research.
Dr. Kevin Crofton: Actually, this is Kevin, if I could take the first stab at that. First thing, it’s, “Hi, Phyllis.” The second is could you send me those references? I haven’t been following that, at all. If there really is an interaction between fluoride and iodine, then I’d be very interested.
Dr. Phyllis Mullinex: Yes. As a matter of fact, one of the professors that’s been doing that type of research – there’s a lot of it going on in China, in particular – will be in this country and will be visiting with me. But they have been working on animal models that combine fluoride levels with the iodine level. They’re definitely showing further increases with lowering of IQ in children. They’ve done both animal models and human studies. I do have a relatively complete listing of those thyroid studies. Like I said, they’re mainly studies that have been done either in the late 1990s to just recently in 2005 studies. I can provide you references.
Dr. Kevin Crofton: That would be great. Thank you.
Dr. Ted Schettler: This is Ted Schettler with the Science and Environmental Health Network. I’m wondering, Dr. Brent, what your advice to women is, now. What I think we’re seeing is that there are some women who know that they’re thyroid-deficient or have sub-clinical hypothyroidism. But their clinical care providers are not aware of some of these issues. Because of the importance of thyroid hormone levels early in pregnancy, how would you advise a woman who is contemplating pregnancy, who is subclinically hypothyroid, in terms of how to approach this, if she’s not getting a proactive response from her clinician?
Dr. Gregory A. Brent: That’s a great question. I’m sure Dr. Haddow will have some comments, also. As Dr. Haddow said, although we’re not at a stage yet to say that the intervention – meaning normalizing thyroid-hormone levels in those women - definitely prevents the adverse outcomes, the reduced IQ in the offspring of preterm delivery. We all think that that’s highly likely – at least, based on the studies so far.
There is some controversy over those women who have been identified with mild thyroid insufficiency, whether they should be replaced. But it’s certainly our recommendation, which is in the reference materials from the American Thyroid Association and CDC conferences is those women should be normalized. In fact, because of the increased requirements during pregnancy – when it’s really a stress on the thyroid gland, the target TSH level – which reflects the amount of replacement – should be toward the low-normal range.
Dr. Haddow alluded to some differences in pregnancy. In fact, the normal TSH in the first trimester of pregnancy is significantly lower than in the normal population or non-pregnant population. The bottom-line is, our recommendation for those women with those qualifications is that they should be replaced to, actually, a low-normal TSH. Meaning slightly elevated thyroid-hormone doses. In fact, that first trimester probably is the most important. And if you wait until that time, you may be missing a window of opportunity, in terms of optimizing maternal thyroid status for the fetus. I’d welcome also Dr. Haddow’s input on the question.
Dr. James Haddow: Yes. I think that we all feel that trying to convince the clinicians involved with prenatal care to try to identify any thyroid problems as early as possible in pregnancy is extremely important. Of course, this is true for the women who are known to be hypothyroid, as well. They need to be attended to promptly.
One bit of supplementary information that might be of some interest is that we had an opportunity to look at blood samples that had been collected from women in both the first and second trimesters of pregnancy. In other words, the same woman would have a sample drawn at 8 weeks gestation and then – say – at 16 weeks. This was for another study that was being done.
Then we turned around afterward and realized that we should have looked at some of the thyroid measurements, as well. We discovered that in the first trimester, a number of the women had - a small number, but predictable - had values in the upper range. In the range that would be considered between just thyroid-deficient and frankly, hypothyroid.
The same women in the second trimester had values that were not elevated. In other words, without anything being done on our part or anything being said or even known, the medical care appeared to have been focused enough on this that the values had come down to or close to the normal range.
There is activity going on at the primary care level that would say to us that the message is getting through. I thought this was quite encouraging, because we did see, earlier-on, that this was not the case when we used the same kind of laboratory evidence to see what was going on.
Dr. Roy Ozanne: I’d like to add a comment, here, and give my experience and that of other physicians who are nutritionally minded. The low-thyroid mother or sub marginally low-thyroid mother – they do wonderfully, well mostly, with nutritional replacement. I’m really talking about food - the type of diet that does that is well described. Since it doesn’t hurt anyone, and it prevents problems in all other organ systems, and delivers beautiful children, I think our primary care physicians in this country really need to get more behind good nutrition. Just a resource was the July issue of “Wise Traditions,” from the Weston A. Price Foundation. It’s a fantastic journal – totally devoted to preconception and pregnancy nutrition and post-natal. It’s wonderful.
Marcia Marks: Yes. I had a question. It’s really a policy question. Whether there’s enough data, now, to recommend testing for all females for thyroid disease. I wanted to use an example: When my daughter was 10 years old, she had Hashimoto’s Thyroid Disease. At age 10, that is. It was only after I was very persistent - because I have some medical background - that I got the doctor to test her. There must be a lot of children and other females who have this type of problem. We have so many radionucleides from the hundreds of nuclear reactors, and all the nuclear waste and endocrine disrupting chemicals. Wouldn’t it be cost-effective to catch all of this hypothyroidism early? Rather than have all these other problems?
Elise Miller: That’s an important question. Should we? Are we at a point where we can now say it should be required of all women of childbearing years – or even prior to that?
Marcia Marks: I think all female children.
Elise Miller: Yes. Thank you. Comments on that?
Dr. Gregory A. Brent: I’ll make a quick comment. This is certainly a major focus of concern. Certainly, anyone with any clinical suspicions or so-called case findings based on family history or symptoms should be tested. When you start to look at screening and questions of cost-effectiveness, you ask questions - which tests should you use - just the TSH or also the free T4 level of thyroxin or antibodies, because the antibodies could also pick up women who have post-partum thyroiditis, for example. Then there is the issue of the timing, which Dr. Haddow alluded to—pre-pregnancy would be optimal. It’s hard to capture all the women that way. The first trimester may be too late, but also may be more predictive of downstream events.
We’re all very interested in, certainly, identifying the women and trying to find the best tests and the way to do it. I think the answer right now, from an epidemiology point of view, and health services is that we don’t have the data yet to promote screening across-the-board for those kinds of questions that I’ve given. We certainly do strongly encourage anyone with any suspicion or risk factors for thyroid disease, which could include other autoimmune diseases – Type 1 diabetes, et cetera – to be tested. We’re trying to push for the testing, and then gather more data to better focus the kind of screening we’d do.
Elise Miller: Thank you. We probably have time for just one more question.
Dr. Vincent Garry: I’m Professor Emeritus at the University of Minnesota. One of the questions that I have is that in Minnesota, we screen for TSH function in the newborn period. There are lots of kids that have transient neonatal hypothyroidism. I’m wondering – should we go back to those mothers?
Dr. Gregory A. Brent: I’ll let Dr. Haddow comment, too. Definitely, some of those moms will be on antithyroid drugs, so the infants will get some of that, and have a transient elevation in TSH. But anecdotally, I’ve seen a number of cases where the moms are not tested, and in fact, do have some transient hypothyroidism. Sometimes there are blocking antibodies or a postpartum thyroiditis. I do think that should heighten suspicion. But Dr. Haddow, I know, deals with this, directly.
Dr. James Haddow: I can give some direct data from the same study I was talking about, earlier. We went to the newborn screening records at the Regional Laboratory in Boston, to see if we could document any information about thyroid deficiency in the newborn, transient or otherwise – among the study subjects of the mothers who were thyroid-deficient. We did not find any evidence in our study. That was a limited in numbers, of course. We had 62 out of 70 subjects.
Dr. Vincent Garry: We’ve got years’ worth of data on these kids.
Elise Miller: We’re going to have to wrap up, now. I’m really sorry to have to cut off comments. I know there were more questions. I just want to take a moment before I turn the call over to Eleni for final wrap-up, to thank all of our presenters. It was excellent. The questions were very informative and useful. Again, thank you to everyone who joined us, today, and particularly to our presenters.
Eleni Sotos: I just want to mention that we have scheduled the February National Partnership call. It will be on February 28th at 9 am PT, noon ET. The subject will be Nanotechnology and Environmental Public Health. Also note that we will be sending out our monthly e-newsletter this afternoon. Please keep an eye out for that. We’ll have some information about the call, as well. I thank everyone. We look forward to seeing you next month on the call. Bye. Thank you.
