Information Living with thyroid disorders TED webinar FAQs TED: More than meets the eye’ webinar FAQs Thyroid Eye Disease (TED), also known as Graves’ orbitopathy or Graves’ ophthalmopathy, is a condition of the eye’s orbit. It occurs mainly in patients with an overactive thyroid (hyperthyroidism) caused by Graves’ disease, an autoimmune disease of the thyroid gland. About one quarter of people with Graves’ disease develop eye problems. TED can also rarely occur when the thyroid is underactive (hypothyroidism), functioning normally and after treatment for Graves’ disease. In our November webinar, opthalmic and oculoplastic surgeons, Miss Rachna Murthy and Mr Jonathan Roos, discussed surgical and non-surgical approaches to TED. They also looked at patients’ concerns around the aesthetic and psychological aspects of this distressing condition. The webinar was chaired by endocrinologist Professor Simon Pearce, who also led an interesting Q&A session. This is a selection of questions answered by our three experts. I’ve got Graves’ disease (GD) but no TED. What are my chances of developing TED? GD is an autoimmune condition. We recognise there are certain antibodies associated with GD that are also associated with TED. However, not everyone’s immune system responds in the same way. We are all very different. So, someone with a very high level of antibodies may have no TED symptoms. On the other hand, someone with a very low level of antibodies may have significant TED symptoms. There were some studies done in the 1950s where GD patients were scanned. These showed that even though some patients had no physical symptoms on examination, a lot of these patients’ scans showed enlarged muscles. So, the vast majority of people with GD will have some degree of TED, even though they may not have any symptoms. Are there risk factors I should be aware of to help reduce my chances of developing TED? The biggest single, avoidable risk factor is smoking and vaping. Genetics also play a role and we cannot, unfortunately, do much about this. We are learning more about triggers for TED. Certainly, infection plays a role too. There is lots of research going into the microbiome, particularly in the gut, and we are looking at the nasal microbiome. Sometimes the microbiome goes a little bit rogue and bad bacteria come in. These can trigger autoimmune disease. We often see, for example, that sinus disease creates changes in the nasal microbiome that can trigger TED. We cannot, unfortunately, avoid this. Another insult to the immune system is stress. It is very difficult to avoid stress, particularly when you have a disease that causes stress and when your hormone levels are going up, which also causes stress. This can sometimes, unfortunately, be a vicious cycle. Patients understandably feel stressed because of their eye symptoms, which makes their autoimmunity worse. So, their TED becomes worse. There are things that can be done to minimise risk though. Avoiding nicotine in the form of vaping and smoking is the single biggest thing you can do to reduce risk. Vaping is, in our opinion, worse because with a vape containing nicotine people tend to inhale more. More research is coming out that vaping can be harmful so it is worth bearing this in mind. If I have treated GD, could stress bring my TED on? We ask our patients at Addenbrooke’s to try and recall any triggers. Anecdotally the vast majority will say there has either been a stressful time or event. This is particularly true in patients without a family history of GD. If your GDis poorly controlled i.e. there are high levels of thyroid hormone (thyroxine) in your body, you are more likely to develop TED. That is why we feel it is so important to work together with other medical professionals as a team to look after each patient. Is there a particular diet or supplements you would recommend to improve my TED once I have it? It is difficult to be prescriptive about this. There’s research about probiotics and how they may be protective to the immune system and autoimmune disease. There was a large Italian study where they added selenium supplements to the diet of patients with mild TED. Patients’ symptoms improved within six months of treatment. However, as the study did not check the baseline level of patients’ selenium in the diet, they may well have been deficient in the first place. TED will also improve, in any case, over a six-month period as antibody levels go down in response to drives and triggers being better controlled. So, it is hard to know for sure of the exact effect of the selenium supplements. A healthy diet, avoiding smoking, considering taking probiotics and avoiding stress are all helpful. Where the TED is mild, selenium supplements may also be beneficial. This can either be in tablet form or by taking 1-2 Brazil nuts daily as they are the richest natural source of selenium Is there anything people can do to improve symptoms? The vast majority of issues in TED patients, even those with mild disease, relate to eyelid retraction, and the quality and quantity of tears being reduced. Consequently, the eyes can feel gritty and uncomfortable. If you imagine the eyelids are like windscreen wipers on the cornea. Because they are retracted, they are not able to clear the screen as well and vision becomes blurry. Simple things that may help are long term use of lubricants even when the TED is inactive as symptoms can persist. If your eyes are sensitive to the sun, wearing wraparound sunglasses may also help. These can also help reduce watering if wind is a trigger. The theory of adding extra pillows when sleeping is that the fluid may drain away when the head is raised. This is fine in the early stages of TED. Once TED is inactive and you have proptosis (eyelid retraction), it is not going to make any difference though. What’s the difference between TRAb(Thyroid Stimulating Hormone Receptor Antibody) testing and TSI (Thyroid Stimulating Immunoglobulin) testing? Why use one over the other? TSI is the antibody specific to GD. It is a stimulatory antibody and the one that causes an overactive thyroid gland.TRAb is potentially stimulatory and inhibitory to the eye and the thyroid gland. We studied TRAb and TSI in 200 patients at Addenbrooke’s. Based on our study, we think that TRAb may be more useful as a measure for activity in TED. For example, 10% of our patients with very active TED had near normal TSI but raised TRAb. However, most of these patients did not have active TED so we cannot be conclusive about it. The TSI will represent the disease activity almost as well as the TRAb in most patients though. So, we do not see an advantage of running a TSI test over a TRAb test. Q. If I receive a Covid-19 or flu vaccination could that make my TED worse by stimulating my immune system? A. Any vaccine stimulates the immune system to a very low extent. Anecdotally, it does not seem to make much of a difference to TED symptoms. For example, even patients receiving immunosuppression treatment do not seem to experience any change in their TED symptoms, they may just feel a bit fluey for a couple of days. In fact, if there is an immune response elsewhere in your body after the vaccination, it may distract the immune response away from your eyes for a period of time at least. How long can it take for TED symptoms to disappear. Will everything return to normal? With GD thyrotoxicosis, the very nature of having high thyroid hormone levels and adrenalin will cause lid retraction. If there is no inflammation and antibodies are not sky high, then the lid very often improves once thyroid levels have been brought under control. However, once there has been inflammation in our body, there is usually scarring and this happens in our eyes too. This can mean as the inflammation settles, and the TED improves, the lid position may not go back to its normal position. This does vary from person to person, as does the duration of TED symptoms. TED can be completely inactive, but a trigger can cause the GD to flare up and reactivate the TED. Or the TED can reactivate without knowing the GD has been reactivated or without any endocrine abnormality. Can TED be a risk for people with hypothyroidism? Yes, hyperthyroidism and hypothyroidism and even normal thyroid function can be associated with TED, though it is much more common in people with hyperthyroidism. We check both TPO (Thyroid Peroxidase) antibodies and TRAb antibodies in TED patients. In the vast majority of patients, both sets of antibodies will be raised. It is the predominant antibody that will determine whether its GD or hypothyroid autoimmune disease. I have alemtuzumab-induced TED with GD and am awaiting a thyroidectomy (removal of thyroid gland). Is this worth pushing for? Alemtuzumab used to treat MS causes the immune system to shut down. These patients get something called the reconstitution of their immune system and about one third of MS patients receiving the drug will go on to develop GD and TED. The antibodies in patients with alemtuzumab induced TED don’t behave in the same way as those in patients with TED not treated with medication. I’ve found that some patients with aletuzumab induced TED have very mild TED, whereas others have some of the worst TED we have had to treat. It varies so much from person to person. We really need to do more research in this area but we do see a quick reduction in levels of antibodies in patients with alemtuzumab induced TED who have undergone a thyroidectomy. Whether you push for thyroidectomy depends on how severe your TED is. Surgery is an insult to the immune system so you don’t really want to be pushing for an operation that is going to potentially be upsetting your immune system further. We normally ask patients to undergo a course of steroids around the time of surgery to reduce the risk of the TED flaring up. During Covid-19 it is probably advisable to wait until you have had the vaccine before going for any elective surgery. In the long term, surgery would be helpful though. I've been successfully treated for GD a few years back. Is there still a risk I could develop TED? If the definitive treatment you received is just stopping your antithyroid drugs as your antibodies have normalised, then yes it can potentially come back. If your definitive treatment for GD is Radioactive Iodine (RAI) then it kills off the thyroidgland but you still retain thyroid tissue in your neck. This can be a source of antigens that your body recognises as being foreign. So, if you have a trigger it cannot affect your thyroid hormone levels and trigger GD antibodies, but it can affect the eyes and reactivate TED. Thyroidectomy involves removing the vast majority of antigens in the thyroid gland. So the theoretical risk of developing TED in the future is extremely small. Is there a role for teprotumumab? Teprotumumab works by blocking the IGF-1 receptor and has been shown to significantly reduce the effects of proptosis. It is, unfortunately, an extremely expensive drug so it is unlikely it will be affordable on the NHS if it comes to Europe. Research is underway to investigate whether existing drugs may be able to block this IGF-1 receptor in a similar way. These would potentially be a more affordable alternative to teprotumumab but more research is needed.