Transcript of the BTF ‘pregnancy and thyroid disease’ webinar Q&A session

This is a summary transcript of our ‘Meet the Experts’ webinar on pregnancy and thyroid disorders held on 28 September 2022.

Our speakers were:

Professor Kristien Boelaert, consultant endocrinologist, Birmingham

Dr Catherine Napier, consultant endocrinologist, Newcastle

Key: KB – Prof Kristien Boelaert, CN – Dr Catherine Napier

Hyperthyroidism and pregnancy

Once definitive treatment has taken place (thyroidectomy) is someone still considered to have thyroid disease?

Once the thyroid has been removed it brings stability and it certainly makes the journey through subsequent pregnancies smoother. But Graves’ disease fundamentally is a problem with the immune system. By removing the thyroid, we do not remove that fault in the immune system, so you would still be considered to have Graves’ disease. We know that following thyroidectomy, TSH Receptor antibodies (TRAb) levels do fall in the months and years after surgery, but I would be keen to see you in the endocrine obstetric clinic in the years following your thyroidectomy so I could monitor you during your pregnancy. (CN)

Should Thyroid Peroxidase (TPO)- or TSH receptor (TRAb) antibodies be checked during pregnancy particularly if the patient is euthyroid? 

If you have a history of prior Graves’ disease, whether or not you have had definitive treatment with radioactive iodine or thyroidectomy, we check your thyroid receptor antibody levels. If you have an abnormality in your thyroid function tests that presents for the first time during early pregnancy, we need to know what your thyroid antibody levels are. There is a key differential diagnosis of gestational hyperthyroidism/transient thyrotoxicosis in the setting of pregnancy, and using thyroid receptor antibodies can help delineate whether it is Graves’ disease or a transient problem with pregnancy. If I am not sure whether or not you have an underlying thyroid problem and I am seeing you in pregnancy, then I will check your TPO antibodies as well because it will give me a guide as to whether or not you have autoimmune thyroid disease. (CN)

The next question is about how to monitor a patient post-delivery.  I presume that relates to your presentation about postpartum thyroiditis and how to monitor thyroid function post-delivery.

So, there is no universal screening postnatally for thyroid problems, but targeted screening would be appropriate if you have a history of autoimmune conditions, autoimmune thyroid disease or a strong family history, for example.

It is very reasonable for your thyroid function tests to be checked three months after delivery if you develop symptoms that might be caused by a thyroid problem. I would encourage you to get your thyroid function tested if you are encountering problems with mood changes, weight loss, feeling unwell or difficulties with breastfeeding. These would all be very valid reasons to have your thyroid function tested and to be screened for postpartum thyroiditis, which we know is a common problem. (CN)

Is there any treatment for high antibodies following removal of the thyroid?

At the moment ‘no’ but watch this space about upcoming clinical studies in Graves’ disease over the next few years. Essentially once your thyroid is removed your antibodies will slowly decline. And after radioiodine as definitive treatment we know there will be a spell in the following three to six months where there will be higher levels of TRAbs. But once you get to 12 months or longer after surgery or radioiodine treatment, the level of those antibodies decline. So, we cannot give you anything to take the antibodies away, but having definitive treatment will encourage them to fall and should make the management of the subsequent pregnancy more straightforward. (CN)

Which antithyroid drug would be your preferred choice (PTU or carbimazole) and what is the suggested dose?

PTU (propylthiouracil) is our preference for the first trimester or for women who are not using secure long-acting methods of contraception and are open to getting pregnant. Once we get past the first trimester, so somewhere between 12 and 16 weeks (opinions differ), it’s best to aim to transfer over to carbimazole. Changing antithyroid drugs can destabilise the thyroid function. During pregnancy we are very keen to maintain stability, but we’ve got to balance the risks of liver function problems (on PTU) and the risks of problems in the developing baby.

The suggested dose depends on the characteristics of your Graves’ disease. Do you have severe Graves’ disease with high levels of circulating thyroid hormones and high levels of antibodies? If so, you are likely to need a higher dose of an antithyroid drug to gain control. That said, we will absolutely dose minimise in early pregnancy, throughout pregnancy, and during breastfeeding. So, the lowest possible dose needed to keep you euthyroid will be what we use. Antithyroid medications can concentrate in baby, so it is a careful balance between your health and baby’s health, which is why a joint antenatal endocrine clinic is the optimal place to be cared for. (CN)

If TSH receptor antibodies (TRAbs) are positive but only just above the top end of the reference range after pregnancy, and thyroid function tests indicate overactivity, is that Graves’ disease or is that postpartum thyroiditis?

It depends on what your antibody status was like before pregnancy. So, if you had a clear, secure diagnosis of Graves’ disease but your TRAbs were declining over time, you need to be mindful of that resurgence of immune dysfunction that we see post-pregnancy and the high likelihood of a relapse of your Graves’ disease. There is often the need for an escalating dose of antithyroid drug therapy in the months and year postpartum. That said, we know if you have thyroid antibodies that you can also develop postpartum thyroiditis. So, it depends a little bit on what was happening with you before pregnancy, or in the early stages of pregnancy, and looking carefully at your thyroid function tests and your antibody levels over time.   

And what about newly presenting thyrotoxicosis, how can you tell whether it is Graves’ disease or postpartum thyroiditis?

If it has not been diagnosed before pregnancy and your TRAbs are positive, you have probably got Graves’ disease. And of course, you can get Graves’ disease without positive TRAbs – just to complicate the picture – but that is our job to figure out. There are other clinical and biochemical features we can use, such as the ratio of your free T4 and free T3 hormones. This can help guide whether you have Graves’ disease or whether you have more of a thyroiditis type picture. We can think about your personal and family history of autoimmune conditions and weigh up what is more likely, but regular monitoring will reveal the answer. (CN)

Yes, I agree. So, a technetium scan is very useful because there will be no uptake in thyroiditis so I find that is a further, very useful tool. The first six months after delivery it is more likely to be postpartum thyroiditis. If it is between six and twelve months it is more likely to be Graves’ disease but none of these things are absolute. (KB)

There is a question about betablocker use during pregnancy and the treatment of gestational hyperthyroidism related to high levels of the pregnancy hormone HTG.

We do not use antithyroid drugs to treat this. Many women will not need treatment at all but simply monitoring. But if you have symptoms of hyperthyroidism we will use betablockers but we will use them at the lowest possible dose. We usually use propranolol and you normally do not need more than two- or four-weeks treatment. It is also worth knowing that if you need treatment for symptoms of hyperthyroidism in the setting of postpartum thyroiditis, different betablockers have different levels of transfer into breast milk. Dose minimalisation is key and propranolol is a reasonable choice. (CN)

Hypothyroidism and pregnancy

If a pregnant woman is severely hypothyroid following a previous thyroidectomy but has good compliance what would you recommend? What other things should we consider to improve the thyroid hormone levels during pregnancy? Are there any alternatives to levothyroxine as a treatment for hypothyroidism in pregnancy?

It is very unlikely that someone with a very high TSH is compliant with their treatment. So, what you should do is increase the dose and I would suggest that we have sufficient iodine replacement as well. But there is not anything else that we can give to someone who is hypothyroid. The replacement treatment here is levothyroxine.

I saw earlier that someone was asking about T3/T4 replacement. It is very clear that T3 does not cross the placenta. So in women who are on T3 treatment or T3/T4 combination treatment, if I have the opportunity of speaking to them before they become pregnant, I say actually when you are trying to become pregnant and during pregnancy I would like you to just be on levothyroxine because we know that crosses the placenta. And it may be if you are on T3/T4 replacement that your thyroid function is actually fine but the baby does not get enough thyroid hormone because T3 does not cross the placenta. The guidelines are very clear that during pregnancy it should be levothyroxine replacement not T3 replacement nor combination therapy. In someone with a high TSH you just need to increase the dose of levothyroxine until you get normalisation of thyroid function and TSH within the target range. (KB)

Following a thyroidectomy are you considered differently? Does overt hypothyroidism mean that you have had a thyroidectomy and should you have thyroid hormone replacement change during pregnancy?

Yes, again the requirements will be the same. What we know is that in someone who has a thyroid gland that is affected by autoimmune disease, and that therefore struggles, will need to increase the dose of levothyroxine because that thyroid gland is not able to make the increased amount. If you do not have a thyroid gland then again it is a very similar situation that you need to increase the dose.

So, anyone who is on levothyroxine replacement for overt or subclinical hypothyroidism, according to our latest guidelines, should increase the dose, ideally by doubling it on two days of the week. But also, and this comes with a caveat, I ask my patients to double it on two days of the week but also that they have a relatively early thyroid function test so that more targeted changes can be made if needed. (KB)

If a person’s TSH is already in the optimal part of the reference range, should they still be increasing their levothyroxine, even if their levels look good?

I would still increase it. So, the only situation where I do no increase the dose, and this is only a handful of women, are those on TSH suppression for thyroid cancer and who are already taking high doses. In those women I would probably do a thyroid function test first before we increase it because we know that overdoing it is also not good. (KB)

Can women take standard pre-pregnancy and pregnancy multivitamins or would you recommend additional supplementation?

Standard pregnancy supplementation vitamins are fine to take. (KB)

Is it difficult to stabilise a patient’s dose of levothyroxine following their pregnancy?

It can be. Like I said, the increased levels of binding proteins will be present for about two more weeks. It can be difficult also after delivery as there can be a degree of postpartum thyroiditis which can do various things to thyroid function. In some patients it can be more difficult to find a balance there than in others. And again, the key is  close monitoring and making regular adjustments to the levothyroxine dose. (KB)

We have a question about checking thyroid function tests in early pregnancy if you have no previous thyroid diagnosis.

That is a very thorny subject: it is about universal screening for all women in early pregnancy. So experts are not in agreement about this. The stance  in most guidelines is that we have insufficient evidence to do universal screening in pregnancy. I think we should do targeted screening so women who are at increased risk of thyroid disease should have a screening. In women with infertility or recurrent miscarriage, again there, the jury is out but I would have a low threshold for checking it. But I do not think that every single woman who becomes pregnant should have their thyroid function checked. I do not think we have sufficient evidence for that.(KB)

What do you think about once weekly dosing for women who have treated hypothyroidism when they go into pregnancy?

A few of my patients have once-weekly dosing. They tend to be people who forget to take their tablets but for some time we have then established them on a once-weekly dose. I have actually taken quite a few women through pregnancy with a once-weekly dosing. So often women who have a very high TSH, and who say that they are compliant, come to our clinic where we give them their levothyroxine under supervision. In most of these women, their thyroid function normalises.

So, is it ideal? No. Is it safe? Yes. And it is better than the alternative which often is having a very high TSH which is definitely not good. (KB)

If women have iron deficiency alongside hypothyroidism how should we approach treating that?

Iron deficiency needs treatment. I tell all my patients that they may well have to go on iron tablets during this pregnancy: anaemia is common, iron deficiency is common.  I tell them to take their iron at least for hours away from taking the levothyroxine. (KB)

Does receiving a diagnosis of Hashimoto’s thyroiditis mean that anything should be done differently when they are on levothyroxine?

No, most people on levothyroxine will have Hashimoto’s thyroiditis, which is autoimmune thyroid disease. This is the most common cause of hypothyroidism in the Western world. So, the fact that they have Hashimoto’s thyroiditis by definition means that they have raised TPO antibodies and if they are already on levothyroxine there is no different approach. If they are not on levothyroxine and they are TPO positive then I think definitely if their TSH is over 4 mU/l  I would treat. But I would probably treat both TPO positive and TPO negative women with a TSH of over 4 mU/l. (KB)

Are there any dietary changes you would recommend to increase the chances of conception when you have a thyroid condition?

No, I think a normal healthy diet is fine. Vegan diets often result in iodine deficiency and I would recommend against those. If you are vegan then definitely take your pregnancy supplements. There is evidence in both vegan pregnant and non-pregnant women that there is iodine deficiency so that would be my only concern. Other than that, a healthy balanced diet with a reasonable amount of dairy is a good plan. (KB)

If a patient thinks they are allergic to levothyroxine what would you recommend?

There is very little evidence that there is true allergy to levothyroxine. Some people are allergic to excipients (fillers), which are the ingredients that bind the tablets together. I have looked at this repeatedly with our pharmacists and actually there is very little difference between the excipients in the different tablets. So, some people feel better on a certain brand of levothyroxine. If that is the case and if you can find that brand then it is fine. The guidance from MHRA (Medicines and Healthcare products Regulatory Agency), which I helped write, states that if patients do not tolerate the tablets or are allergic to certain forms then liquid levothyroxine is an option because that has less of the excipients. However, that is more expensive and therefore often GPs do not like prescribing it. But liquid levothyroxine may be an option in selected cases.(KB)

The final question is about what antibody levels should be aimed for?

This is a bit of a bugbear for me! So, we do not aim for antibody levels. Generally, I think it is a good idea to measure the TPO antibody levels in someone who has thyroid disease but there should be a single measurement. Because our treatment (levothyroxine replacement) is not governed by the level of antibodies.  

I often get a patient who has antibodies of 200 and then I get a letter saying that their antibodies have gone to 600. As long as you are replaced on levothyroxine then that is fine. Similar to TSH receptor antibodies (TRAbs) we don’t have any treatments to address antibodies. There is some patchy evidence that selenium might make a difference but I do not think that it is very strong and good evidence. So, I think what you need to do here is to address the thyroid function and look at TSH and free T4 measurements. (KB)

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