Autoimmune expert: Dr Mark Vanderpump is an endocrinologist specialising in thyroid disease and reproductive endocrinology including PCOS

In this episode, I interview a leading Endocrinologist based in London, Dr Mark Vanderpump, on autoimmune diseases, with a special focus on thyroid conditions. 

In this episode, I ask him: 

• Why are women more imapcted by autoimmune diseases than men?
• What are autoimmune diseases and why do they occur? 
• What are the autoimmune diseases triggers and treatment 
• Conflicting researching surrounding increases and decreases in rates of autoimmune disease 
• His view on lifestyle medicine and how gut health might impact 
• Why is there a delay for so many women when it comes to diagnosis 

About Dr Vanderpump

Dr Mark Vanderpump is a consultant physician and endocrinologist OneWelbeck in London, specialising in thyroid disease.

Dr Vanderpump is a highly experienced endocrinologist. He was a Consultant Physician and Honorary Senior Lecturer in Endocrinology and Diabetes at the Royal Free London NHS Foundation Trust for 17 years, until he moved to full-time private practice, in 2016, after more than 30 years working in the NHS.

He is the past President of the British Thyroid Association (2014-2017), and a 2017 and 2022 Top Doctors award winner. He is the former Chair of the London Consultants’ Association.

He is a published author with a book and chapters on thyroid disease, and he regularly contributes to medical publications and teaches and lectures nationally and internationally.

Transcript

In this episode, we'll speak with Dr. Mark Vanderpump about autoimmune diseases, with a special focus on Hashimoto's and thyroid conditions. We'll speak about what is an autoimmune disease, why it disproportionately affects women, what can trigger an autoimmune response, and why there may be a delay in diagnosis. One key takeout from this episode for me was to ensure that you're eating a diet rich in iodine, especially if you're thinking about fertility or if you're pregnant. Dr. Vanderpump explains why in this episode.

So thank you, Dr. Mark Vanderpump, for joining us today on the Living Hellth Podcast to speak about autoimmune diseases with a special focus on Hashimoto's and thyroid conditions. So to set the scene up for the listeners, there's around 80 known autoimmune diseases, and unfortunately, 80% of those impacted are women. Hashimoto's is just one of the types, but it is, I believe, the most common autoimmune thyroid disease.

Now, before we jump into the questions, before we get started, I like to ask my guests a bit of an icebreaker question that I think is quite indicative of health, either around cycles or sleep. But of course today I'm gonna ask you about sleep and how you slept last night, and how do you find sleep generally? 

So anyway, having been warned I'd be asked about my sleep, I've reflected on this lot. I would say that until COVID I was actually okay. I found that really disrupted my sleep pattern thereafter. It might just be coincidental with my age. The other factors—I've got a lateral fat impingement of my knee, which has kept me awake last night, and also, but I've been partially helped by West Ham winning a couple of football matches, which has helped my stress levels this week specifically.

That's good. That's good. Good to hear it. I wanna start with a bit about you for our listeners—your area of expertise would be great.

So I'm a consultant endocrinologist, so I specialise in hormonal conditions. My career was in the NHS for 30 years, but for the last seven years or so, I've been just in private practice. I was based at the Royal Free Hospital. My research and the main focus of my specialist area within endocrinology is thyroid disease. And I was involved in a research project many years ago that looked at the long-term outcomes of people in the population who had abnormal thyroid function tests and what happened to them within a 20-year follow up. So that's how I made my name in terms of my research background and my MD. And then since then, I've just kept my thyroid research going and I was the former president of the British Thyroid Association.

Mm, yeah. You've done so much in the space outside of your day-to-day work. Can I ask why did you go into this area of medicine?

When you are a junior—we're not allowed to call them anymore—resident doctor, when I was a junior doctor as we were called then, you rotate through various specialties and so you get a flavour of where. And I must admit, I'm practically completely useless. So if anything involved putting a tube in anyone or doing anything, any procedure, I was a disaster. So I quickly learned I needed a talking specialty. And so endocrinology worked well with that. And then I worked for a guy called Simon Walford in Wolverhampton, who was quite influential in my early career. He got me started, I went to Newcastle, I did my research, and so I've just stayed within it ever since.

Now, let's start with the basics. What is autoimmune disease, and then what is Hashimoto specifically? 

So autoimmunity essentially means that your immune system has made an error—i.e., it should be fighting a bug or a virus. And for reasons we'll discuss, it starts turning on the body itself. And so the autoimmune—you're starting to make an antibody that's fighting something within your own body. It's not fighting the foreign agent, essentially. So it's not really quite clear. It might just be due to the location of the thyroid and its particular susceptibility, but thyroid disease is within this box—you mentioned 80 tablets.

When I talk to patients, I like to talk about a box of autoimmunity—the thyroid circle is the big circle in the middle, and then on the edge there are satellite circles outside that, but they're all in the box. So for example, if I see a person with thyroid disease, I'd be telling them they've got a much higher chance of getting vitiligo, which is where you get white patches on the skin. I might say there might be a 1% risk. If I go to a vitiligo clinic and see a hundred vitiligo patients, I'd be expecting about a quarter of them to have thyroid disease. Although these other conditions within the autoimmune box are still rare in thyroid patients, they're much commoner than in the general population; the satellite autoimmune conditions often have thyroid coexisting with them at the sort of 25% level. So other conditions are lupus, rheumatoid, and pernicious anaemia, alopecia.

As you said, there is this sort of—the box is more common in women and there are reasons why that might be the case. In terms of why women do get autoimmune disease, in terms of thyroid disease specifically Hashimoto's thyroiditis, which we'll discuss later, is that it's about 10 times commoner in women than in men. And one of the—I remember during the COVID pandemic—is that there was this thing where men had worse outcomes than women. And so there was this reason why, you know, and it was said men's immune system might be slightly weaker. So the downside is that you have a worse effect from an actual infection, but you then have a lower rate of autoimmunity. And there might be something within our evolutionary biology that women have a better immune system, so they're better able to fight COVID, but they also seem to have this increased predisposition to develop autoimmune diseases at the same time. So it's a bit of a double-edged sword: benefit in one way, less chance of COVID illness, but or bad outcomes compared to the men. You remember there was a sort of three to two men to female outcome difference. But it is quite interesting why that has always happened.

But in general in autoimmunity, what you inherit within this box is you inherit a predisposition. So you just—you have to have the genetics—and then what you need with an autoimmune disease is to meet something in the environment that triggers the production of the antibody. So there might be loads of us walking around with the potential; we will still need another event before we get the disease. The other argument, particularly with thyroid disease for women, is that there is an increased risk with pregnancy in the menopause. So the peak age of getting Hashimoto's thyroiditis is in the sort of fourth, fifth decade. So again, the endocrine causes might be relevant as one of the triggers for autoimmunity, which obviously men don't have the same.

So for example, within three to six months of a pregnancy, autoimmune disease is quite common of any type, but particularly thyroid disease. And that's because your immune system comes down in pregnancy, particularly the second half, to allow the baby to grow and develop. Then as soon as the baby's born, your immune system wakes up and there's an immunological switch. So you switch back to your previous immune state and it's thought that trigger somehow is the initiating event that triggers the thyroid antibody as your sort of autoimmune phenomena.

Oh wow. So we have the genetics, but then it's the trigger that unlocks the— 

Yeah. So the idea would be—but I mean there's been some very good twin studies looking at evolving. So the best—I say the best one in terms of it's been 'cause it's easy to follow—is with type one diabetes, where there was some famous twin studies many years ago based in Kings. And so they followed twins; so they watched Twin one get diabetes and then they followed twin two. And so what they showed—they, i.e., both twins, identical twins, had the same genetics. And then when twin two was being followed, they saw him develop the antibodies about six to nine months before his sugar went up or her sugar went up.

So you've got this sort of natural history and observation that you develop the antibody, it starts attacking the pancreas, you reach a point where you're not making enough insulin, and that's the point your sugars go up. And we see a similar phenomenon in an overactive thyroid, which is called Graves' disease. And Graves' disease is similarly thought that usually within six to nine months—often a bit sooner—you develop the antibody and then it's that, that then triggers the thyroid overactivity two, three, six months later.

And when thinking about typical symptoms, what symptoms do you see commonly and maybe uncommonly in some of your patients? 

So specifically on Hashimoto's thyroiditis, the one of the common observations is that thyroid disease in the community is quite common. So if you look particularly in middle-aged women, about 10% of them can show evidence of thyroid antibodies, and about half of those might show their thyroid starting to struggle. So what we have in our brain, in our pituitary gland, is a monitor—like a shop steward—looking down at your thyroid factory, okay? And what you make is a hormone that reflects your economy; so it drives the thyroid production.

Now the thyroid gland is a fairly straightforward gland. It's like a factory being asked to make a hundred cars a day. You make more when you're pregnant. But other than that, the amount of cars you make is fairly standard. Whether you're stressed, quiet, exercising, it's a fairly constant amount, and that amount is genetically set. So we know that because when people have thyroidectomies—when they take their thyroid out—you give them thyroid, thyroxine back, there's quite a wide range of dose. Some people need 75, some people need 300 micrograms. So there's no right or wrong dose; it's what you need.

And so when we say how much do you need, what we look at is not the level in the blood, but actually what the shop steward thinks. So the TSH is the main—is for thyroid stimulating hormone. It's made by the pituitary gland, and it's made in response to the amount of thyroid you have in the bloodstream. So the pituitary monitors the T4 and the T3. Just to make it clear, T4 is the main hormone we make, but it's inactive—it doesn't do anything. The four relates to the number of iodine molecules on the T4. You have to take one iodine off to activate the hormone. So T3 is the hormone that does all the action of thyroid hormone; so there's a clever enzyme called a deiodinase that takes the iodine off to create your active hormone.

So when you're taking thyroxine, for example, you're just topping up a reservoir. You're a muscle cell and need some thyroid hormone action, you pull in the T4, you take off one of the iodines, and that gives you your active hormone. So the pituitary gland is monitoring that process, seeing how much T4 and creating this TSH. So the amount of TSH you make is proportionate to how well your thyroid economy is. And so we have a reference range, which we define as being what's measured in the healthy population of between 0.4 to 4. As a sort of—if you measure a hundred people, that's normally there; 95 of them are between those two numbers, which also means that 2.5% of healthy people are below and 2.5% of healthy people are above those numbers. So a reference range is a guide—it's not like you have to be within those.

A nice example, I think, is that when a baby's in the womb and developing, there's a one in 3,000 chance that you're born unluckily without a thyroid gland. So you are okay in the womb because you're getting your thyroid hormone through the placenta from mum. But when you are born, you're then on your own, okay? Now, congenital hypothyroidism is pretty serious 'cause if you've got no thyroid hormone in the first couple of years of life, you get permanent brain abnormalities and poor development, and it was one of the commonest causes of sort of mental retardation many years ago.

So the brain actually—long before the baby looks like it is—there is a clinical syndrome with underactive thyroid baby, but long before the baby can be detected as having it clinically, the pituitary gland has noted that you've not got a thyroid. And so the TSH is rising almost immediately you are born. And so when the midwife does a heel prick on babies on day five, they're measuring the amount of TSH. And if the TSH is quite high, then you know the baby's been born without your thyroid.

So the point I'm making is that within five days, the pituitary gland is screaming at your thyroid gland saying, "Where is my hormone? I need it now". And so you can use the TSH. So the point is that within the natural history, as we say, of thyroid disease, your shop steward is right on it all the time, so any minor increase or decrease in production, your pituitary gland is working to bring you back in line and say, "No, I don't want 105 cars a day, I don't want 95—I just want a hundred cars a day". It's a bit like having an air conditioning system where you set your room temperature at 70—the moment you go to 69, your radiator kicks in; the moment you go to 71, the air conditioning kicks in to bring you back level.

So the point of that actually is that the TSH and the pituitary gland is telling you there's a problem long before the person in the room knows there's a problem. So you and I might walk in a room at 60 degrees and say, "Look, this is freezing, what's happened here," but at 69, 68, we might still be there and not notice. So we've got this early warning system almost to tell you. Within the community, lots of people have early warning systems and signals that things aren't quite right; they don't necessarily know the room temperature has changed. And so when people have been looking at populations, they would say, "Okay, we'll go to a health fair and we'll measure thyroid function in 20,000 people from Colorado or something". And they get them to do a questionnaire, they measure their thyroid function, and then they correlate the symptoms with the blood test and see who've got it.

Now, one of the problems with thyroid disease—particularly underactivity—is there's a long, wide range of symptoms which are quite common in the population. For example, in this famous Colorado study, about a quarter of the population—now you have to remember, this is Colorado, I dunno their quality of life, I'm assuming it's good, I think it's pretty good in Colorado—but a quarter of the population were tired, miserable, overweight. There was a general feeling that a quarter of us are unhappy most of the time. Yeah, and until your TSH got to a certain level, statistically you had to be more miserable than the background population to detect a difference.

So we feel that—so when people are being given treatment targets or diagnoses, it's more that there are data around which should tell you when people start noticing the change in the room. So for example, that's why in the thyroid world they've chosen 10 as the sort of cutoff for this TSH number, because it's at that time that the symptoms start appearing more and you've got more chance of it having a benefit. So if there's more marginal elevations, the patient or person would often not detect it. And also, again, many years ago, they put people in those more marginal situations into randomised trials with thyroxine supplements or placebo, and not all of them detected which side they were in. And a lot of people who were given thyroxine dropped out of the study because they felt worse on thyroxine.

So it is not—sometimes there's a bit of trial and error, and it depends on how the person's come to you. So if you go screening in that Colorado health population and they're at a health fair, they're presumably quite well and they wandered in. Having said, if you are a 55-year-old female teacher who's having a tough time, and they have the blood, there's a difference in how we approach a single individual and how they're diagnosed in what circumstances versus somebody who's been found as part of a population screening. So there's a little bit of a difference in how you approach a population versus the individual in front of you, which sort of means that some people, for example, may notice the change in the temperature in the room much earlier than someone else. So a lot of the medical statistics are based as a group; so that's why it's sometimes difficult to define 'cause you can clearly have individuals who behave at different ends of that spectrum and might benefit or not—so that's giving you a background of how the data has evolved over the last 30 years.

How to track those symptoms and then lead to— 

Yeah.

So what would you say is the most common symptoms and especially the early signs? 

Yeah, I just say the other slight issue here is that the timing of the peak incidence correlates with the menopause. So certainly in women—men slightly different, come back to that—but in women between 40 to 60, they would often assume they're tired, gaining weight, dry skin, poor quality hair. They might assume it's the menopause, for example, and it's their thyroid. Equally, they could have a thyroid condition that's treated and not know that their symptoms are caused by the menopause. So one of the issues—the patient population at higher risk—there's a strong overlap between the two states and so you can misattribute your symptoms to the menopause when actually it's your thyroid, or vice versa. So I think it's just making people aware that you're allowed to have both conditions and not assume one is not the other.

Yeah, that is quite interesting. I spoke to the menopause expert this morning and it's so hard to get the symptoms and understand—is that vitamin deficiency or is it the menopause or perimenopause? It's hard. 

One of the interesting concepts I've come across is that because it's so difficult and because the questionnaire scores are so useless, is that what I've described to people is what's called a retrospective awareness of disability. It means that—here's your blood test—assume your TSH is eight; you're uming and ahing—do you want to take thyroxine? Within three months, you can get the TSH back to the perfect level of one or two or something. And then at the three-month point, you say to someone, "Do you feel better or not?" If you do and you actually say, "Actually I now, you know, blah, blah, blah," you can say, "Great, you're on it and you're fine". If you feel worse, you can stop taking it. So you are allowed an individual treatment trial to determine whether someone wishes to or justifies the replacement therapy.

You spoke about it then and how you identify it in the population versus individual experiences. Some studies showed that the global prevalence of, I think it's Hashimoto's has increased; others show that it's decreased—it's confusing. What would you say to that? 

The overall suggestion is that it's probably more case finding than true increasing in incidence. You've got to come out with a theory why autoimmunity might move more pro. Now there are reasons why that might be excessive hygiene, for example, compared to our history. There are general theories as to why autoimmunity might be more common, but in general, I suppose within the thyroid, I think there's much more awareness and much more testing. So I think if you went to your GP 50 years ago, I think it was quite a struggle to get your thyroid tested, whereas nowadays there's a much lower threshold, more thyroid awareness. People are being tested; they're being tested more around pregnancies or the menopause. I just think—so it is difficult to know whether there's a true increase or whether you've just got increased case finding because you've just got more aware, both medical and, but actually more importantly, the patient population. 'Cause it's often them saying, "Can I have thyroid disease?"  Yeah, okay.

And the doctor can't say yes or no without a blood test. So, well, I think sometimes the patients now are demanding more testing as well because they've read that it could be a cause and it's a simple thing to exclude—you've got a good blood test, let's see if you've got it or not. So I think it's difficult with all that going on to know whether there's a true increase—sort of like ADHD; it's like—is it increasing or are we just getting better at diagnosing? 

I don't think there's much evidence that the thyroid antibody status has increased, by the way, in terms of autoimmunity, in terms of the available population studies. But even that's a bit more difficult because I was involved in a study that looked at thyroid antibodies in the early seventies—we repeated it in the early nineties. Even between those two decades, the technology for measuring thyroid antibodies has changed. So sometimes your detection, because you've just got better assays, can actually give you an apparent increase as well. Of course. So there are methodological reasons why things can increase; it may not just be a true increase.

Okay. I thought it was interesting that you cover PCOS as well. How does that link to autoimmune disease? Obviously, I know it's hormonal—part of our endocrine repertoire of the conditions we assess. 

Now, there's no clear link between PCOS and autoimmunity. You mentioned endometriosis earlier—actually, there's not much evidence of that either; people really don't know much about endometriosis. The problem is that I'm seeing mostly a female population for the reasons we've talked about, and PCOS, again, if you look hard enough, may be present in a quarter, 20% of the female population. So sometimes there's a bit of coexisting bit of data—in terms of what's called insulin resistance, which is the main cause or driver probably of polycystic ovary syndrome. The polycystic ovary syndrome genes are linked to type two diabetes, so that the genetic pathway is different.

Type two diabetes is not an autoimmune disease. There is some evidence in certain circumstances that insulin resistance might influence your thyroid function, but in general, I suspect most of us would see them as two separate conditions and not intrinsically linked. But again, the symptoms of PCOS can be quite tricky and often would prompt a check of thyroid function. So again, you're into the disease acquisition—that if you come and see me, I'll probably check your thyroid with your PCOS; I probably would find you—if you hadn't come with your PCOS, I might not have done the test. So again, it can just be case acquisition. So I don't think there's a true relationship and I don't treat PCOS women on the basis of their thyroid; they're treated separately.

Okay. That's really interesting. I read somewhere that you can get multiple autoimmune diseases at the same time. Is that true? 

Yeah. So there are some—within this genetic package, some people can present with two or three or four autoimmune diseases at the same time. Yeah, so once you are in—once you've got your big thyroid circle in the middle—how many of the 1% satellites you collect is a bit determined by your genetics. So there are what they call polyglandular syndromes, where you're affecting more than one organ. So the commonest one is usually the adrenal gland, where you get what's called Addison's disease, where you don't make cortisol. If I go to a type one diabetes clinic, I probably find about a third of the young women will have thyroid autoimmunity.

So some of these sort of satellite conditions can appear in families together. So we don't screen for them, but you're on the lookout for those other conditions; but you tend to be more readily screening for thyroid disease in the satellite conditions 'cause as we've talked about, the prevalence is so high in them. So that's what we call case finding in a high-risk group. Whereas the population screening is a bit more—maybe 50 is the ideal age for a woman type thing—because that, or maybe in and around pregnancy. So there are some key moments when you would screen, but there are certain conditions where you'd be more active on your screening programme.

You spoke about it before, but I just wanna have a clear question and answer on: why does autoimmune disease affect women so much more than men? 

So I don't think there's a clean answer to that. As I said, I gave you a few postulated theories. As I said, I presume that men have the same genetic risk, but they still need the trigger. I could see a man presenting with an autoimmune disease at 85 years old—he's had the genetic predisposition all his life. He's had a load of stress; he's probably had a load of different diets and whatever environments. What made it appear at 85 suddenly out of the blue when he's had that risk all his life? It's very difficult to know and that's why, although we speculate a little bit—'cause I think patients quite like a narrative. So if they get a disease and they're diagnosed at 45, they'll say, "Why has it happened?"  They say, "Okay, I got divorced last year." Sometimes it's actually quite difficult, particularly with Hashimoto's, 'cause as I showed with the 20-year study, is that you can have a 20-year lead-in time. So if you are diagnosed at 45, you could have had a blood test at 25 that showed you were potentially at risk. So your initiating event was more than 20 years ago; it just took another 20 years for it to fully declare.

Okay. And maybe thinking about autoimmune diseases, but also Hashimoto's—what are the biggest myths and misconceptions you see maybe in your day-to-day, maybe online? 

I suppose in general it should be a fairly straightforward condition to diagnose and treat. The treatment is essentially risk-free. You're replacing the T4 your body wasn't making; so instead of you making the a hundred cars a day, you get given the a hundred cars a day every morning with a tablet that—if I'm a muscle cell and I need some T4 and I pull it in from the bloodstream—I can't tell whether you've made it yourself or whether you've got it from Boots that morning on a prescription. So it is almost the perfect replacement strategy because you're taking a single—I mean if you told a diabetic patient on insulin injecting five times a day that the alternative is a once-a-day tablet, they'd be in a dream world, frankly. So in theory we've got the ideal answer.

I suppose what we don't do is go back to the problem and say, "Okay, let's find out why your immune system's gone wonky and can we do anything to prevent it?" Because the system was so easy to replace, we give up on the failure. I just give you the hormone back and say, "Forget why it happened, but here's the answer in terms of the tablet". I suppose it's the more difficult thing to answer. So I think the difficulty for us is that often people are presenting at a later stage when the damage is almost done. So if you're going to employ that tactic, you probably needed to know five years before you got the condition, not 25 years when you're on the inevitable slope of decline.

So I think that's the difficulty, 'cause people do want something they can do to change the outcome and there's very little evidence anything that we can do in term—what I would call lifestyle measures—that really change the outcome. And I suppose the one that people talk about most is going gluten-free. And, but I always think if you said to me, "Look, I've had my measles jab and I'm immune to measles now; if I just go gluten-free, do you think my immune system will forget measles once it's got the template?" And it's making the antibody—it's quite difficult to think it's gonna suddenly switch off just because I've gone gluten-free, for example. There's a bit of a theory about your gut microbiome driving the autoimmune process—maybe through that sort of mechanism.

So I think in terms of myths and difficulties, I suppose it's more people struggling to understand, and in that sort of world where there's no real answer, you are also struggling with autoimmunity often being a fluctuating process. So you can see naturally antibodies—so if someone's got multiple sclerosis, for example, you can see them having periods of remission, relapse, doing a pattern like that. And you can see it in thyroid disease as well. So when you're doing an intervention, it's difficult to know whether you're just observing what you might expect is the natural history or whether your intervention is truly calmed down the immune system—that's the problem. So the difficulty is those studies probably would take 20 years and they're just not gonna happen.

There's a lot of people on thyroxine in this country; I think it's about 5 million. It's about the second most prescribed hormone or tablet in the whole NHS. And it was a colleague of mine in Cardiff who looked at the diagnostic blood test at the start and maybe 15, 20% of them had a normal blood test before they started their hormone supplement. And then one study that looked at people who'd been on thyroxine for a few years and just re-evaluated the original diagnosis—and about a third of them didn't need it. So there is quite a lot of probably overtreatment.

The idea is that when you've got a funny blood test, you watch and wait for a bit to see if you've got a definite problem, whether you've got a naturally improving problem, and there is good evidence—certainly within the TSH range less than 10—that a lot of people spontaneously improve and get better. So if you dive in quite early, you can be on thyroxine and not know you are in the group. So until you revisit the diagnosis years later, you wouldn't know whether your thyroid had actually recovered or not.

Have you seen any of your patients being able to manage their autoimmune disease through lifestyle, like maybe alongside or instead of? 

I must say I never stop anyone doing anything they want to do. That's the first thing. So whatever they feel comfortable with—all I'm saying to them is that as a conventional endocrinologist, it's not that I tell you this is what you now need to do, but if someone comes back to me and says, "I've read up about going gluten-free"—I must say there's quite a lot of low-grade gluten intolerance in the population. They might come back and say, "I feel so much better then"—I'm not gonna say don't do it. Whether it's gonna change the outcome of their thyroid disease is a bit less clear, but certainly their perception of health might be better; but we don't give them the thyroid diet, if that makes sense.

And do you think that—I guess it's hard 'cause you said things might have improved for them if they had known five years earlier—but there's no test that is widely available to just know five years earlier. Are you sort of hopeful with where tech is going, where those tests are going? 

So when looking at this 20-year follow-up study, there are a couple of main observations. One is that within what they call the normal range of this serum—this mark of this serum TSH—the people towards the upper end of it were in a higher-risk group than were previously suspected. It's not that they're symptomatic at the moment; it's that they're in the group who over 20 years are more likely to become underactive. That if you look in that group, they tend to have a few more antibodies, and they tend to be in that group. So when you start looking at 20-year predictors, you can actually—from a baseline blood test and thyroid antibody profile—actually determine your risk of becoming underactive within 20 years of needing thyroxine.

So although across the population, if you've got a good blood test now, antibodies are probably less than 1%. If you've got a borderline raised hormone and some positive antibodies, the chance of converting is about 60%. If you've just got the antibody, it's 25%; if you've just got the blood test without the antibody, it's about a third. So you can give people a risk. And that then means that over time you can say, "Look, you make sure you have an annual blood test"—you dunno when it's gonna happen.

And also, particularly in younger women, you give them a sort of instructions in and around pregnancy, 'cause as I mentioned, pregnancy has got a high risk of inducing autoimmune thyroid disease if you've got the predisposition. So again, you might tell a young mom to make sure she has a blood test before the pregnancy, during, and importantly, three months after to see if she's in the group that's more likely. 'Cause again, particularly after a pregnancy, a lot of women would attribute symptoms to just being pregnant and that's how you're supposed to feel, which is the common thing everyone tells me. So sometimes thyroid disease—again, like the menopause—can get undiagnosed because people are assuming it's related to the pregnancy, not another condition that hadn't been thought of.

So how do they get that test? What if they don't know if it's in their genetics? 

Well, yes, you don't know your genetics. That's one thing. So the antibody test at the moment is recommended if you are in an at-risk group or if you've got a borderline test to help you make the decision at the moment. I suppose with increasing access to private clinics, people are getting the antibodies done more routinely, but certainly within an NHS environment, you'll get a straightforward look at the thermostat of me—what's my TSH doing? You wouldn't get the antibody test until you've got some abnormality within that first screen. That's just the standard rules at the moment. Whether there's any benefit in knowing the antibody from the start is a bit more disputed 'cause you've got—in any screening programme—you've got to look at cost-effectiveness: either the cost of doing the assay, what you do with the information, what you then do thereafter.

So it's not quite as simple as people think, even just a simple blood test to know over 20 years did the population benefit. So actually knowing something doesn't always offer you a health advantage. A screening programme which is evidence-based looks at the people who are harmed and those who are benefited. It's quite more nuanced evidence-based than people just say, "Oh yeah, fine, but it's much better if I know you've got antibodies or not". And then the other—it's a bit like, again, if people do all these sort of imaging screening now where they have everything scanned, but if you have a normal scan in August, then you develop symptoms in December, what people tend to say is "Oh I was all right in August, I was fine". They don't get the new symptom looked at. So again, you can be falsely reassured by the normal scan and not look at a new symptom. There is a harm in a screening programme as well as a benefit, and obviously if you're found to have cancer and you're cured, then obviously that's a great outcome, but there's a group who are falsely reassured and a group that are falsely alarmed as well as the people who benefit.

Now moving on to diagnosis. What's the journey look like for someone? 

In the UK now, there are probably two ways that you get diagnosed. One is you go for a health test—a health MOT, or some of your GP or your work medical or something. So you'll then have a blood test which shows the abnormality. So the assumption on that is you've gone in well, you've not got symptoms or not—you don't know you have yet. Obviously that comes back to the retrospective awareness issue we discussed. So you are told you've got an abnormality and then you do something about it or not.

The other one is the more individual case where someone comes into their GP and they'll say, "I've just had my menopause, but I'm on HRT, but I'm still really tired and there are other symptoms". And then they're given a blood test to exclude thyroid disease. So one of the things about the pituitary gland, as I was saying earlier—by the time someone's got symptoms, the blood test is usually quite obvious. I.e., at the point the room temperature has changed that you and I know it's either hot or cold, the pituitary has been screaming at you metaphorically for months and years and says, "Look, I've been telling you for ages, you've just not been listening".

So actually by the time someone's got a symptom, and if you said to me, "Look, I feel really tired at the moment"—if your TSH is 1.5, I can almost say the only thing you haven't got is thyroid disease because it's so comfortably normal that it would've—by the time you had the symptom—you'd be expected the biochemistry to be clear cut. There's gonna be one or 2% that doesn't fit. I'm just saying as a general health-based policy. And indeed, some clinics still just use that as their only test of thyroid function; they don't even do any others at all. At a population level, I'm talking—when you do millions of tests in a community, there is a reasonable evidence base that's not a bad screening test. There are things that you miss—obviously when you do that, you miss people who are going up and down. You miss people who've got a pituitary problem. So the TSH test is reliant on you knowing you've got a normal pituitary function. So for example, in pituitary disease—low libido or poor erectile function in men; in women, it might be hot flash.

And that sort of brings you on to some women feeling like they aren't getting the diagnosis early enough, or they don't feel listened to, or they don't get the full panel of testing—how can they advocate for their health better? And why do you think that delay exists? 

One of the problems in this area generally—'cause it's quite a common—there are two sort of things, I suppose. One is that within the undiagnosed group, there's quite a high prevalence of thyroid antibodies in there—it would be in Hashimoto's. It doesn't necessarily mean that your thyroid has yet malfunctioned. So if your TSH is still normal and you've got the antibodies, you've got the condition, but your thyroid factor is still managing, 'cause if you weren't producing less than you needed, the pituitary gland would've told you.

The theory on that is that the general state of autoimmunity tends to be debilitating. So if I speak to a rheumatoid patient—"My joints are doing this or that, but I still feel generally knackered". So there is a sense in autoimmunity—it can be draining on you physically without necessarily being the thyroid being the cause of your symptom. And that's similarly the other way around—and the people who have all those symptoms, they've got the thyroid condition, they get given thyroxine, they don't always feel better. So we have that as a probably say, "Look, actually your blood test perfect now, we've got you exactly where you want it to be, where your brain says this is where you've been genetically," and yet they'll say, "I've still got all the symptoms I had before". So to give you an example, those are two situations which are difficult to manage—it's not that doctors aren't listening, it's more how do you then move ahead with that as a problem because you're a bit stuck.

I wanted to ask you, just moving on slightly: what is drug-induced thyroiditis and why would that happen? 

Okay, so if you're looking at the population who developed thyroid failure, they fall into two groups. One is called spontaneous and one is called post-treatment for hyperthyroidism. So the people who have an overactive thyroid can receive a treatment that makes them underactive, and that's about a third of cases in the community. In worldwide terms, iodine deficiency—if it's severe—can cause underactive thyroid. In Europe, although we're low in iodine—particularly in young women, which may have implications in terms of pregnancy and childhood development—it's not a cause of thyroid failure per se.

So if you're then looking at this sort of—the two-thirds who get spontaneous thyroid failure—the majority, vast majority, will be Hashimoto's thyroiditis. Their immune system attacks the thyroid, and that's why they're deficient. There's a subgroup—a small group of people with thyroid disease—who have it caused by a drug they've been taking, and the commonest ones historically have been drugs like lithium, which they use for manic mood disorders. There's a heart drug called amiodarone, which has got a heavy amount of iodine in each tablet, and that can block the thyroid and cause it to fail or also be stimulated.

In the new world, actually one of the commonest causes we see is the new immunotherapies. So people who have breast cancer or other cancers—they're often put now on these new magical immunotherapies, which are giving great outcomes. And I saw somebody this week who'd been treated for breast cancer, and she developed a thyroid problem six months after being treated with one of these new therapies. And actually the data on that is quite interesting because the patients who develop the thyroid problem seem to have better outcomes than those who don't. So actually, I usually say to them, "It's great that you're seeing me, 'cause if you've had this reaction to your thyroid, it usually means the tumour has been attacked successfully by the immunotherapy as well". And the interesting thing is though—although it's behaving like a Hashimoto's thyroiditis, they don't have the same antibodies. So it is an unusual mechanism as to why they get a very completely similar picture to what we'd see in Hashimoto's, but they haven't got the antibody presence that we'd expect if it was genuinely autoimmune in terms of the standard autoimmunity. So in my practice, those would be the three commonest types.

Okay. And now moving on slightly to sort of treatment. You've already mentioned the medications that you would prescribe. And we've already spoken about that nutrition and things like that aren't really something you prescribe.

But I'd be doing that for everybody—yeah, what you're talking is a healthy lifestyle that should apply to everyone, not specifically those with thyroid. What I'm saying is, I suppose it's not very thyroid-specific, but there might be ways to enhance your health with a diet and exercise programme that can complement thyroid management.

Yeah. What I was going to ask is how you thought gut health specifically can be linked to autoimmune diseases—could you talk about that? Is it linked? 

Yeah, I'm not sure in terms of the theory, as it were. That it's—as I understand it—that you can have gut microbial populations that are linked to certain diseases and that you can make dietary changes that change that population and that somehow that lessens the impact or reduces. So as far as I'm aware, that's still quite speculative and unproven, but it's the theory. In terms of the cause or what's triggering the autoimmunity, it's one of the potential theories being discussed at the moment as to whether there is something—your gut health or gut microbiome—that's generating the autoimmune response.

You probably spoke a little bit about it before, but in seeing where care for autoimmune diseases has moved in the last 10 years and the technology to come—how do you think it compares and what are you most excited for? 

In terms of thyroid disease management, I suspect that not much has changed over the last 50 years, almost since I started training. So in terms of the underactive group—as I mentioned—we still are not yet in a position where we offer someone immunotherapy to prevent the ongoing autoimmune destruction of the thyroid. We still concede it's better to give you the hormone replacement rather than try and have the side effects or whatever of immunotherapy.

I suppose in that world, there's more discussion regarding the role of combination therapy where there's a hormone called T3. So I mentioned earlier that the active hormone is T3. Although you are given conventionally T4 alone and you convert the T3 from the T4 'cause you have an enzyme that does it, there are about 5% of patients estimated—it's difficult again to get true figures, but in that sort of range—who just don't have a perfect blood test and don't feel better, and particularly those who have had a thyroidectomy as well, which is a removal of your thyroid gland.

So in that group, there is a reasonable chance that some of them may benefit from switching their regime to what we call combination therapy, which is more mimicking the normal physiology. The theory is that if we're making our pool of T3, which is our active hormone, if we've got a functioning thyroid gland, about 80% of it comes from the T4 and this remove of the iodine. But in normal health, we'd make 20% of our pot direct. So if you haven't got a thyroid gland, you've got to make a hundred percent from the T4 because you've got no supply line of your own. So some people combine T4 with T3 as a way of mimicking normal physiology. So that's something we try in this group who are not better symptomatically despite having an optimal thyroid function test on the conventional replacement. So I think that's become more mainstream as a practice over recent years.

In terms of the overactive group, there are three main treatments there. There's a tablet that can calm the situation down; there's an operation to remove your thyroid; or there's something called radioiodine, which can kill off the iodine cells. Both the surgery and the radioiodine tend to create an underactive state, which you then replace with levothyroxine. And again, I think historically people were given radioiodine much more commonly than they are now.

And I think more recently on that side, the drug role and having repeated drug courses of drugs and/or perhaps staying on the drug long-term is a sort of a patient preferred option. This is becoming increasingly used in management, whereas historically, I suspect it was always more process driven—that in terms of the NHS management of follow up, if you were on thyroxine, you were discharged to your GP and that was it. If you're on carbimazole, you have to stay with the specialists. So I always felt we were finding a way to enable the discharge, but increasingly patients are choosing to stay on a long-term dose of a drug to calm the thyroid down rather than get rid of the thyroid and take a tablet to bring it back up again. So I think that's interesting.

There's also work on people who have bad thyroid eye disease—so there's something called thyroid orbitopathy. 'Cause particularly in the people who have an overactive thyroid called Graves' disease, about 20% of them, the antibody that's attacking the thyroid gland to turn up the dial and make extra hormone also attacks the back of the eye so people can present with prominence of the eye, swelling, inflammation. So there are some new antibody treatments around looking at targeting, 'cause that's a pretty devastating complication of thyroid disease, particularly in young women, 'cause it doesn't take much to change your features and people to recognise there's a problem. So it's a really debilitating long-term outcome of thyroid disease management and it's a major cause of poor quality of life scores.

Okay. And then maybe thinking about prevention. Say if someone's had their genetics tested or they've seen their mother go through something similar, what kind of things should they be thinking about? 

As I said earlier, I'm not sure there's much evidence that anything you can offer them in true prevention. The main advantage and what I would tell—so if I saw a chap yesterday with thyroid disease, I might say, "If you've got any daughters—you got two—how old are they? Twenties and they're getting pregnant"—I might just say, "Look, if you've got thyroid disease, your daughter's risk of thyroid disease has gone up from 5 to near 20%, even higher". It's more about increased surveillance and testing and being thyroid-aware.

I suppose it's more awareness, and so if they're seeing their GP and they've got a funny symptom, thyroid's included in the package of testing, or if they're pregnant, it's made sure it's optimised. 'Cause on the pregnancy it's particularly important because outside mum and her symptoms is that there's a crucial role in keeping the thyroid hormone environment optimised during the pregnancy for the baby's development. So particularly during the first 12 weeks, the baby's completely dependent on mum. You've got to make sure mum's thyroid hormone status is optimised. So once the baby's about 14 weeks old, its own thyroid is started to work; so it's pretty okay from then on. Yeah, if it's still working—of course we come back to the one in 3,000—it never did.

So the first 12 weeks are particularly crucial, and there's the one we call the physiological changes of pregnancy is that your thyroid makes an extra 25 to 50 micrograms when you're pregnant. So if you're on thyroxine, you need to anticipate the rise because you know you're not gonna make it yourself. So if I've got a woman on a hundred micrograms a day, I'll be telling her as soon as your pregnancy test is positive, you go up to 125 a day, do a blood test a couple of weeks later, make sure it's all okay. You might need a further increase for the remainder of the pregnancy; you get them thyroid aware.

And the other issue on that in more general population is it's increasingly recognised, particularly in the UK, that women are iodine deficient. So even if they've got normal thyroid function tests, a low iodine status in mum may have an impact on the baby's development, obviously, 'cause iodine is a crucial part of thyroid hormone production. So the British Thyroid Association are really trying to, again, trying to make the government, et cetera, iodine-aware because it's a bit of an unrecognised problem in this country specifically, particularly affecting young women who are the ones who are likely to get pregnant. And there are various reasons for that, possibly due to change in milk intake, 'cause about half our iodine tends to come from milk. So if women suddenly drink oat milk or move to other alternatives and just don't drink milk anymore, they've suddenly lost a lot of their iodine content in their diet. And that even at subtle levels, again, may have implications on the baby's neurodevelopment.

That's really important and really interesting. I didn't know that. A couple of last questions here. What advice would you offer a listener—in the first season we're focusing on women's health—so maybe a female listener who is struggling with an autoimmune disease, a piece of advice that you would give to them? 

What I suppose in terms of the—there's a recognition that the state of autoimmunity can give you symptoms in its own right. You are allowed to feel tired or flat because you've got an autoimmune disease—what you can address is the direct cause of the problem. So in the thyroid world, we can say, "Look, we can optimise, we can help support." So when you are addressing your autoimmunity through your lifestyle, you can know you've got some comfort in knowing that your thyroid status has been optimised. And so sometimes it's the reassurance—that they can park that to one side and focus on the other side—I think can be helpful.

The other thing, as I mentioned earlier, particularly with other conditions, is the awareness that thyroid is a common condition. If you've got any of the other satellite, rarer autoimmune conditions, then the thyroid is quite a common coexisting one. So just make sure you're getting it periodically tested. You could ask for the thyroid antibody to determine your risk. You've got to accept that things can be normal and change. So if you're okay in 2020 but you're not in 2025, you get the test repeated. As I've said earlier, once the room temperature has changed, the blood test will tell you.

Mm. Okay. Great. Thank you so much. We're actually at time.

Very good