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CASE NOTES
Tuesday 1 April 2008, 9.00-9.30pm
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BRITISH BROADCASTING CORPORATION

RADIO SCIENCE UNIT


CASE NOTES Programme No. 1 - Thyroid



RADIO 4

TUESDAY 1ST APRIL 2008

PRESENTER: MARK PORTER

REPORTER: LESLEY HILTON

CONTRIBUTORS: MARK VANDERPUMP


PRODUCER:





NOT CHECKED AS BROADCAST

PORTER
Hello and welcome back to a new series of Case Notes - as usual we'll be covering a diverse range of medical conditions over the next nine weeks, including herpes, knee problems, and the latest thinking on sciatica and prolapsed, or "slipped" discs. And there is still a chance to get in touch if you want us to cover a particular subject - I'll be giving you the details of how to do that later on.

But first today's programme - which is all about thyroid disorders.

The thyroid is a butterfly shaped gland lying under the skin just in front of the voice box. Despite weighing in at just 20g - less than an ounce - it packs a major punch thanks to its ability to manufacture and secrete two hormones that influence the metabolism of every one of the trillions of cells that make up the body.

I'll be discovering what happens when the thyroid goes into overdrive and produces too much - a condition called hyperthyroidism - and how it can result in some unusual effects.

CLIP
Well I couldn't hold anybody's gaze because I knew that in holding a gaze my lids were retracting and I looked as though I was staring and when you stare you do look aggressive, you tend to have your chin lifted up so that you can see because there is double vision often and that also makes you look quite aggressive.

PORTER
And I'll be talking to a man who is concerned that as many as 1 in 40 pregnant women could have an under active thyroid gland, and that if it's not picked up - as it often isn't - it could have major repercussions.

CLIP
Nineteen percent of the children born to mothers who had a mildly abnormal thyroid function had an IQ of less than 85 aged seven years, compared to 5% of the controls. And that was highly significant.

PORTER
My guide through the thyroid maze is Dr Mark Vanderpump, he's an endocrinologist at the Royal Free Hospital in London.

Mark, we will be focussing on what happens when things go awry in the thyroid a little late on in the programme, but perhaps we should start by explaining how levels of thyroid hormone are controlled when everything is working normally.

VANDERPUMP
Well thyroid hormones are produced by the thyroid gland and there are two important hormones - T4 and T3. And the four and the three relate to the number of iodine molecules that are incorporated into the actual hormone. And the T3 is the so-called active hormone but the majority of hormone that's produced is in the form of T4 and one of the ID molecules from that is taken away mostly in the liver, so that the T3 is then available to enter into cells and exert the thyroid hormone action.

PORTER
And what's it actually doing at that cellular level?

VANDERPUMP
Well in essence it's in charge of our metabolism, so it keeps the engine running, it makes the cells work normally, utilise oxygen. And so therefore if you're lacking in thyroid hormone things tend to become sluggish and slow down. If you've got too much hormone they raise and you tend to become more agitated and over active.

PORTER
Now those levels of T3 and T4 are crucial - too much we run into trouble, too little we run into trouble - so how are they tightly regulated?

VANDERPUMP
Well the main command centre for the endocrine glands in total and for thyroid gland as well is the pituitary gland and that's a tiny pea shaped gland at the base of the brain which produces a hormone called TSH or thyroid stimulating hormone. And the pituitary gland monitors the level of thyroid hormone in the blood in a very sensitive fashion and then controls by sending out the signal TSH to the thyroid gland so that we carefully regulate the amount of T4 and T3 that we produce.

PORTER
So too much you don't produce any TSH or very little, too little and it produces a lot of TSH.

VANDERPUMP
And that's called the negative feedback principle.

PORTER
So what goes wrong? Let's start with people who produce too much hormone - hyperthyroidism - what's causing that in most cases?

VANDERPUMP
Well in most cases it would be due to something called Graves' disease, which is what we call an autoimmune disease, so that's a disease in which the body produces an antibody, so normally these are proteins that we produce to fight viruses and bacteria, and this antibody actually targets your own thyroid gland, so it's autoimmune, and actually stimulates the gland to make more thyroid hormone than you need. And the antibody is actually closely mimicked, the TSH receptor, so actually the thyroid is responding appropriately to a protein produced by yourself to make you make more hormone.

PORTER
And who's most likely to get Graves' disease?

VANDERPUMP
Well it would be about 8-10 times common in women compared to men. And it tends to be younger women as well. But the peak incidence would be in the menopausal years between 40-50 years.

PORTER
And how might a woman know that she was running into trouble, what sort of symptoms do you get if you have too much thyroxin?

VANDERPUMP
Well you have palpitations, you might have increased bowel frequency, you feel sweaty, you feel agitated, a woman's periods might stop. If it was a man they might lose their libido. You might exhibit some of the other signs of hyperthyroidism in Graves' disease, such you might feel your thyroid is swollen and that's called a goitre.

PORTER
A swelling of the front of the neck.

VANDERPUMP
A swelling in the front of the neck. And you might notice the eye signs which can be present in a proportion of people with Graves' disease but not all.

PORTER
Well those are all symptoms that would be all too familiar to Janis Hickey. She was diagnosed with an over active thyroid in the early '80s - but only after she developed problems with her eyes.

HICKEY
I do remember waking up one morning and thinking that my eyes felt a bit peculiar and they were quite sore and I realised that I was blinking quite a lot. So I went to the first aid box, as people probably do and probably shouldn't, and got myself some golden eye ointment out and stuck that in my eyes, thinking that whatever it was would go away. And then a few weeks later it hadn't improved so I took myself along to the doctor who told me that I had conjunctivitis. So gave me some drops. And I suppose during that time I realised that I was looking a little bit different, when I looked at myself in the mirror I thought that I looked as though I was staring. And I do remember at the time we had a family photograph taken, I just thought that I looked quite different from what I'd normally look like. So then I took myself back to another doctor and had a blood test and sure enough I realised I was told that I had an over active thyroid gland and thyroid eye disease along with it.

PORTER
Did you have any symptoms, looking back now, of the thyroid trouble?

HICKEY
Yes, yes, when I look back I realise that actually I had all the classic symptoms but it was a question of putting them together to make the full story. By the time I was properly diagnosed it was November and at that time I'd started opening windows in the car - you know and it was quite cold outside - and opening windows at work and people were saying to me what are you doing, you know, and now I realise that that was one of the classic signs. I also had lost quite a lot of weight, so I was down to just under eight stone, and I was particularly anxious and fraught and irritable and blew my top at anything really. I remember putting my hands over my eyes and thinking oh they feel a little bit prominent and I did mention this to a friend of mine who was a nurse and she said oh well maybe you've got a thyroid disorder. Discussing it later with my parents I discovered that my maternal grandfather actually had Graves' disease and had thyroid eye disease but I unfortunately never knew him.

PORTER
Presumably once your thyroid problem was diagnosed the doctors treated that but what did they say could be done about your eyes?

HICKEY
Well the eye situation was really just left. They said soothing words like oh well it will get better, it could get better and I wasn't referred to an ophthalmologist - an eye doctor - for quite some years really, it was a long time afterwards. And of course by that time the damage had been done.

PORTER
And when you saw the ophthalmologist how was it explained to you, what were you told was actually going on in your eye?

HICKEY
Well I was told it was connected to the thyroid disorder itself and that the muscles at the back of my eye had actually increased in size. And that they were therefore pushing my eye forward. I was staring and blinking a lot and then the eyes did move forward to the extent that I had the appearance of looking as though I was always angry or frightened. And it was that that caused quite a lot of distress to me because I could see how I was changing. And although I had very good friends and family who said it didn't matter at all to them, there were outsiders who would look at me and occasionally pass comment.

PORTER
So by this stage when you went to see the ophthalmologist you were told that a lot of the damage had been done, what treatment were you offered?

HICKEY
The very first thing that I was offered was some drops which I believe relax the eyelid so that it wouldn't retract so much. But those actually made my eyes very red and bloodshot. But then I kept pursuing things because I was determined that something should be done. So the very first operation that I had - I've had nine operations altogether - was to stitch the corners of my eyelids together. The effects were okay for a start but you can imagine with the pressure of the eyeball behind the lid it didn't really last very long and actually the stitches gave way, the skin gave way, and I ended up with the same shape as I had before. So then I had various other operations, one to drop the top lid down and then I went really for the operation that really sorted things out for me, which is called orbital decompression and for me it changed everything. I didn't look like I used to look in 1984 but then nobody does do they.

PORTER
So after that - that major surgery - you felt that there was a distinct cosmetic improvement, you felt much more comfortable?

HICKEY
Yes, yes.

PORTER
And that was noticed in other people's reactions as well?

HICKEY
Oh yes, yeah, I remember my brother saying oh got the old Janice back, that was lovely, it was really nice to hear that.

PORTER
And looking back and when you had your first operation in 1984 how have things changed for other people that you meet with thyroid disease, is treatment of this problem better now than it was?

HICKEY
Yes, absolutely. I think there's more recognition amongst doctors that the psychological effects do have a massive impact on people. Whereas in my day I really had to fight to get this operation, I was told that I was within the range of normal. It's changed now and there is a greater understanding of the patient's perspective of how they feel and that is felt to be important.

PORTER
Janis Hickey, who is now Chief Executive of the British Thyroid Foundation, talking to me earlier about hyperthyroidism and her resulting eye problems.

You are listening to Case Notes, I am Dr Mark Porter and I am talking about the thyroid with my guest endocrinologist Dr Mark Vanderpump.

Mark, could Janis's prominent eyes have been prevented had her condition been diagnosed earlier?

VANDERPUMP
There's certainly very good evidence that early treatment recognition and correction of your thyroid status can prevent the progression of thyroid eye disease. Although in some cases you can see it have a life of its own, presenting before, during or indeed many years after the episode of thyrotoxicosis.

PORTER
And what sort of proportion of people are affected?

VANDERPUMP
Well if you looked hard enough on scans you might say up to 50% but in terms of people who notice the symptoms down to 20% and I think 5% would be a rough figure who present with such severe symptoms that they need help like Janice did.

PORTER
Can you quickly run through the treatment for an over active thyroid?

VANDERPUMP
In essence there are three treatments: there's drug treatment which we would offer for about 18 months normally; there's surgery which is more historical treatment ..

PORTER
That's to remove part of the gland...

VANDERPUMP
Just to remove the gland itself and the third way to remove the gland to prevent it being a problem is radio iodine, where you incorporate a very low level of radioactivity into an iodine molecule, that enters the thyroid gland and locally destroys the thyroid cells, making the gland shrink, shrivel and not make any thyroid hormone anymore, where you become under active afterwards in most cases.

PORTER
Because that's the problem with surgery as well isn't it, it's judging how much of the gland to remove or destroy with radio iodine and that's where I want to move on to next is the under active gland. Besides people who've been treated for an overactive gland who's likely to get a hypothyroidism or an under active thyroid?

VANDERPUMP
Well again it's much commoner in women, compared to men, and again it tends to peak at around the menopausal years, so in the 40s or 50s.

PORTER
And the telltale signs would be?

VANDERPUMP
Well lethargy would be one of the most common, people feel swollen and oedematous, they might notice swelling of their eyes or their ankles; constipation, dryness of the skin; thinness of the hair; periods might become heavy or stop. There's also an association with other autoimmune diseases such as diabetes, pernicious anaemia and other conditions as well. But ...

PORTER
It's much more common than an over active thyroid isn't it?

VANDERPUMP
Well in terms of the population about 1% of women have had an over active thyroid and probably up to 2-3% of women are on thyroxin, so it is generally much more common to be under active.

PORTER
What's your stance on the widely held belief, certainly if my post bag's anything to do by, that the tests that we use are too crude and that they miss people who have vague symptoms like weight gain and fatigue who feel that they might benefit from a boost in their thyroid levels?

VANDERPUMP
Yeah I mean this is a really big issue for most endocrinologists and the - I mean one of the important things to remember is that thyroid disease - particularly hypothyroidism - presents with very non-specific symptoms. And so there have been surveys that have suggested a quarter of the healthy population would be hypothyroid if you were simply being diagnosed by a questionnaire alone. What we have in the pituitary is a very closely regulated system, so that the very smallest changes in thyroid levels, either too much or too little, will produce a big change in your TSH level. And so the pituitary is the most sensitive part of us that monitors thyroid function.

PORTER
And the bottom line being if your TSH is normal you're suggesting that if you've got symptoms you look elsewhere for them rather than at your thyroid?

VANDERPUMP
Absolutely, the one thing to just remember is that the thyroid gland may not be the issue and sometimes the pituitary gland can fail, so that you have to make sure that this is on the assumption that you have an intact and working pituitary gland.

PORTER
Okay. I want to move on to pregnancy now. Around 1 in 500 pregnant women will have some degree of hyperthyroidism which, if not managed properly, can cause problems for both mother and baby - including miscarriage, premature labour and heart failure.

But under-activity - hypothyroidism - is much more common. As many as 1 in 40 pregnant women will have low or borderline hormone levels. John Lazarus is Professor of Clinical Endocrinology at Cardiff University Medical School and behind the Controlled Antenatal Thyroid Screening - or CATS trial - designed to find out if pregnant women should be routinely screened. I asked him what was likely to happen if the condition was missed?

LAZARUS
Probably the most important complication that has emerged over the last 10 years or so is the realisation that the IQ of the baby might in fact be impaired. That has been studied with young children but also in children up to about the age of seven.

PORTER
And that's because the mother's circulating levels of thyroid hormone have a direct effect on brain development do we think?

LAZARUS
Yes we do think that. There's quite good evidence from animal studies, as well as human studies, that thyroxin, the main thyroid hormone, gets into the baby through the placenta and is responsible for aspects of brain and nervous system development. And in the first trimester the baby doesn't make its own thyroxin, so that it's really critically dependent on the mother's level of thyroxin for that development. It's also dependent on it right through pregnancy but obviously not quite so much because it makes its own thyroid hormone about 12-14 weeks.

PORTER
One of the problems is a lot of these women will have borderline under active thyroid that are often missed, how do we know what impact they're having on the children later on because presumably you don't know what the woman's thyroid function is like during her pregnancy?

LAZARUS
Well that's a very interesting question and that has been addressed. A few studies, some from Holland and one very big study reported from the United States in 1999 when they actually kept the sera - 25,000 sera - from pregnant ladies and then measured the thyroid function later on and so they were able to go back to women who had an abnormality in thyroid function but did not have it treated and compare that with a very carefully matched set of control women and look at their children as well.

PORTER
And what sort of differences are we talking about in terms of IQ, is it a significant gulf?

LAZARUS
Well in the study I've referred to from the North East of the United States 19% of the children born to mothers who had a mildly abnormal thyroid function had an IQ of less than 85 aged seven years, compared to 5% of the controls and that was highly significant. Now it's true that not all the psychological variables studied in that study were significantly different and that overall global IQ was different.

PORTER
You're involved in the CATS study I understand, could you tell us a little bit about that?

LAZARUS
Yes. Well we wanted to see whether we could get prospective evidence as to whether screening for thyroid function would be worthwhile. So to that end we have recruited 22,000 women less than 16 weeks pregnant and randomised their blood samples to either testing or not testing at that time. And in the tested ones if they've been - showed signs of an under active thyroid we've given the mothers thyroxin. In the non-tested ones we haven't tested them until after the babies have been delivered, so that we've now got two groups of children whose mothers have had an under active thyroid in early pregnancy. And we're in the middle of testing those children aged around just over three years for their IQ.

PORTER
And we won't pre-empt the results of the study obviously but one would suppose from what you're saying that intervening by giving the mothers thyroid supplements would protect their children's development?

LAZARUS
Well that's the hypothesis and that's what we're hoping to prove.

PORTER
We already test new born babies routinely for their thyroid function, we do routine tests on mothers for other things, so we have needles in their arms, we're taking blood samples from them, why don't we add thyroid tests to that if it's such a common problem?

LAZARUS
Well I think personally there's a good case for doing so, it's a very common condition, there is effective treatment. I think there is justifiable caution though, especially from our obstetric colleagues about the introduction of any screening test and it's got to be proven by evidence base to be significantly worthwhile. And there is no prospective data in relation to this strategy on the planet and that's why we're doing this study. So I think when the data are in and the trial has been done and if it's positive then I think we have a much sounder evidence base to strongly recommend this sort of thing.

PORTER
Do these women with borderline results have any detectable symptoms, could we be screening them by asking them how they feel?

LAZARUS
Probably not is the answer. Of all the women who are found to have abnormal thyroid function tests only about 1% of them have definitive hypothyroidism, that is a low T4 and a high TSH. The rest have a borderline low T4 or a high TSH. And they're really relatively asymptomatic. Women have complaints when they're pregnant anyway so it's difficult to dissect that out. So what we're saying is that for the moment women who have a family history of thyroid disease or other autoimmune disease or other problems that could be related to thyroid they might be more at risk and they ought to be tested.

PORTER
Professor John Lazarus talking to me from our studio in Cardiff.

Dr Mark Vanderpump, just remind us of which women might want to talk to their midwife about being tested? We heard there about people with family history of thyroid problems, who else?

VANDERPUMP
Well a family history of what we call other organ specific autoimmune diseases, that's diabetes, and also whether you've got those specific diseases yourself. And if you've had a history of thyroid disease in the past. So a lot of women have had Graves' disease 10 years prior to a pregnancy.

PORTER
And of course some women already have an under active thyroid before they even become pregnant and if you're going to be tested you might as well be tested before you even conceive to try and get things normalised.

VANDERPUMP
Yeah, I mean it's important to recognise that the baby is dependent on the mother's thyroid hormone status for the first 12 weeks of the pregnancy, so that's the crucial stage that you need to have normal thyroid hormone. So I think it's important for the mother to get her thyroid function checked prior to conception if possible or as soon as she knows she's pregnant. And we also recognise that women need an extra 25-50 micrograms of thyroxin during a pregnancy and that's needed in the earliest stages, not later on in the pregnancy.

PORTER
So present early rather than late, something to talk about to your doctor before you conceive rather than after.

VANDERPUMP
And to get regularly checked during the first 12 weeks of the pregnancy.

PORTER
Mark we haven't mentioned cancer yet, can abnormal thyroid hormone levels be a sign of a more sinister underlying problem?

VANDERPUMP
Thyroid cancer tends to present with just thyroid nodules and we don't associate either under-activity or over-activity with thyroid cancer.

PORTER
A lump basically.

VANDERPUMP
A thyroid lump yeah.

PORTER
But most lumps we find in the thyroid will not be cancerous.

VANDERPUMP
Well it's also important to recognise how common thyroid nodules are in the general population, so if you passed an ultrasound scan over every neck in London you'd probably find a third of the population would have thyroid nodules even very tiny ones. The problem is, is finding the very few that turn out to be thyroid cancer.

PORTER
Well to find out more about thyroid cancer we sent Lesley Hilton to Newcastle to meet Kate Farnell, and the team looking after her.

ACTUALITY
Hi Kate, how are you doing?

Hi Petros, I'm fine thanks. Feeling a bit tired but other than that okay.

Okay. Apart from that has anything else changed since the last time we met?

Yes I think I'm putting weight on. No matter ...

HILTON
Kate Farnell is at the Northern Centre for Cancer Treatment at Newcastle General Hospital for her regular check up with her consultant. She developed thyroid cancer eight years ago when she was in her 40s. Dr Petros Perros is a consultant endocrinologist in Newcastle. What does he think causes thyroid cancer?

PERROS
We know that there are certain cases where there is a genetic pre-disposition and that is the minority. It tends to be the mendullary thyroid cancers and in certain cases there is a faulty gene which predisposes families to develop thyroid cancer. We also know that exposure to radiation predisposes people to it but in most cases we really don’t know what causes it. And I think one way of thinking about it is that it's probably bad luck that a number of series of events happen to the same thyroid cell which causes its genetic content and predisposes them to produce cancers.

HILTON
Most people who have thyroid cancer will die of something else. The most common types of the disease are the papillary and follicular sorts. They are known as the differentiated cancers and have the highest rate of successful treatment with around 80-90% of patients being cured. But there's another rarer type called anaplastic - and that is a much more aggressive cancer which tends to kill within a matter of months.

ACTUALITY
I need to have a feel of your neck Kate, okay?

Okay.

Look forward, just look straight at me and swallow for me. Excellent. Very good. I'm going to feel from behind. Very good. Head down just a fraction, thanks.

HILTON
Kate had follicular thyroid cancer. Her only symptom was that one day she noticed that the side of her neck looked swollen. She had a scan and a biopsy and then surgery to remove her thyroid before she could begin radioactive iodine treatment. She found the whole thing very difficult which wasn't helped by having to be in virtual isolation because the treatment made her radioactive for a time.

FARNELL
It was awful I was particularly tired and very depressed. My son was coming up to his 13 birthday and we ended up having a Bart Simpson cake with all of us in bed eating the cake because by that time I was just so flat, miserable, my face was all puffed up. I went deaf in one ear and I actually had to go to theatre and have a grommet put in because of the build up of fluid. So yeah pretty awful time, pretty awful time. Dealing with all of that on top of the two operations and knowing that I had cancer.

HILTON
Consultant oncologist Dr Ujjal Mallick also works at the Newcastle centre. He outlines the treatment options for the different forms of thyroid cancer beginning with the differentiated type.

MALLICK
The treatment options available for that particular cancer is surgery first, followed by radioactive iodine. Radioactive iodine actually acts as a magic bullet for this particular cancer and in addition to radiation therapy, radioactive iodine, these patients also need a lifelong high dose of thyroxin which is necessary to keep another hormone called TSH well below the normal range. The mainstay treatment for medullary thyroid cancer is surgery. Radiotherapy has no - very little role, radio iodine actually has no role for this particular cancer. For anaplastic thyroid cancer the vast majority of patients are elderly and the disease presents itself late and very little could be done in the majority of cases.

HILTON
Kate is now doing well and living a normal life again although she'll always need regular checkups.

FARNELL
My prognosis is excellent. I am coming up to eight years on now. I've gone through all of the protocol of having treatment, having a number of what we call challenge scans to make sure that the treatment has been wholly successful. I will never be discharged from care. For the first five years it was pretty intensive - every four months, every six months, and now it's just once a year. I have good quality of life, although I have to be honest and say I don't feel the way I did before all this happened - I can't do as much, .I get tired.

PORTER
Kate Farnell talking to Lesley Hilton.

Mark, on a slightly different note, I've got some salt here, iodine used to be routinely added to table salt in the UK but doesn't seem to be any longer. Are thyroid problems becoming more common as a result?

VANDERPUMP
Well there are two issues. Firstly, historically, we were iodine deficient and this explains the Derbyshire neck, which was the thyroid gland growing and responding to the lack of iodine in the diet and indeed a third of the world is still iodine deficient.

PORTER
Derbyshire because it's presumably away from the sea?

VANDERPUMP
Away from the sea. And it's to do with the water, the iodine in the water supply. Nowadays we're considered to be iodine replete and we don't need to take any iodine supplements routinely.

PORTER
You do hear about people taking supplements - iodine supplements - natural seaweed and things, kelp, to improve their thyroid health, is there any evidence that that can help you with your thyroid?

VANDERPUMP
Well not really, is the answer, and there are two issues. One is if you've had an over active thyroid or are at risk of an over active thyroid iodine can actually precipitate that event.

PORTER
Yeah, act as an accelerant.

VANDERPUMP
And secondly, if you're on thyroxin replacement you've got your thyroid hormone ready made and you don't need iodine anymore because you're taking it within the molecule itself.

PORTER
Dr Mark Vanderpump, we must leave it there, thank you very much.

Don't forget to contact us if there is something you would like us to look into - you can e-mail us via the Case Notes website at bbc.co.uk/radio4 - where you can also ask for the programme to be sent to you as a regular podcast so you will never miss it again. And if you don't have access to a computer then you can call the Action line on 0800 044 044.

Next week I will be visiting a busy sexual health clinic to discover the latest on herpes infections, and trying to clear up some of the misunderstandings that so often surround chicken pox and shingles. 

ENDS


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