I had a chat with Dr Petros Perros yesterday about a member that was contemplating continuing her carbimazole treatment when she should be stopping it because she has neutropenia (an abnormally low concentration of neutrophils (a type of white blood cell) in the blood) and was afraid of having RAI treatment. People with neutropenia can then go on to get agranulocytrosis (an acute condition caused by lowered white blood cell count). Dr Perros was concerned about this member and offered to write something about this issue and he sent it to me this morning:
A patient of mine sent me an email this morning about a post that appeared in Healthunlocked about agranulocytrosis. As a result, I contacted Lyn Mynott and we had a useful discussion about whether patients with agranulocytosis can switch to another antithyroid drug, or reduce the dose, or have radioactive iodine, and if so are there concerns about radioiodine and cancer.
What follows is some information about agranulocytosis, which in the middle of the present pandemic is probably more relevant than ever. Please note that the British Thyroid Association (BTA) and the Society for Endocrinology (SfE) are about to make a statement about patients with thyroid diseases and Covid-19, so look out for it. At this time, I have no access to the draft statement by the BTA and SfE, and I hope that what follows is not contradictory; if it is, I apologise and recommend that you follow the BTA/SfE recommendations.
Agranulocytosis is a rare and potentially life-threatening side-effect of antithyroid drugs (carbimazole, methimazole and propylthiouracil). The chance of developing agranulocytosis is 0.2-0.5% (Vicentre et al, 2017) and in most cases it happens within the first three months of treatment.
When minor side-effects occur with one antithyroid drug (eg rash), switching from carbimazole (or methimazole) to propylthiouracil (or the reverse) is helpful, however, this strategy is not recommended if a patient has developed agranulocytosis (Ross et al, 2016), as the risk of developing the same or more severe episode of agranulocytosis is of the order of 15.2% (Mayer-Gessner et al, 1994). This may not seem high, but given that it is life-threatening it has to be weighed against the other alternatives of treating hyperthyroidism, which happen to be much safer options, therefore there is consensus among thyroid experts that switching antithyroid drugs in this particular scenario is unwise (Ross et al, 2016).
The usual alternative treatments are radioiodine and thyroidectomy. I have been advised by my Medical Physics department that radioiodine may be available throughout the corona pandemic in the UK, although in our centre we are recommending that patients who are stable on antithyroid drugs defer radioiodine treatment, largely because of the likelihood of instability of thyroid hormone levels afterwards, which is considerable and will mandate extra blood tests and adjustments of medication dose.
In special circumstances there are some other options that can be considered, but they are not be as effective as radioiodine, anti-thyroid drugs or thyroidectomy:
1.If the patient is young and fit, is tolerating the symptoms of thyrotoxicosis, and has no plans to get pregnant, then treatment with a beta blocker alone for a few months is highly unlikely to cause any long-term harm.
2.Cholestyramine is an old-fashioned drug for treating high cholesterol. In the gut it binds to lots of chemicals including thyroid hormones and increases their excretion. Cholestyramine has been used instead of antithyroid drugs to treat thyrotoxicosis (Nayal and Burman, 2006, Lin et al, 2013).
3.Lithium carbonate has also been used (Suwansaksri et al, 2018).
4.Iodine can be used for the short-term management of hyperthyroidism, but only specifically in preparation for surgery (it reduces thyroid hormone levels very effectively in hyperthyroidism, but only for 1-2 weeks, then the thyroid overactivity can come back with a vengeance).
With regards to the risk of cancer following radioactive iodine treatment, it is very easy for anyone who is trying to make sense of the literature to get confused.
Firstly, a distinction has to be made between patients with thyroid cancer being treated with radioactive iodine from patients with hyperthyroidism. Thyroid cancer patients receive three or more times the dose of radioiodine that we use for hyperthyroidism. In high doses (as for thyroid cancer) there is a very small increased risk of another cancer developing in future.
The literature on the risks of cancer in patients treated with radioactive iodine for hyperthyroidism is mixed. There are some very reassuring studies showing no excess risk (reviewed in a meta-analysis by Hieu et al, 2012).
However, a publication in 2019 by Kitahara et al, (2019) highlighted that there is an increased risk. On the other hand the most up to date information (Gronich et al, 2020) is reassuring. A likely explanation for these discrepancies is that the studies that show a risk (eg Kitahara et al, 2019) included patients who were treated several decades ago when doctors used to give multiple small doses of radioactive iodine.
That is in contrast to what we have been doing in the last 20-30 years, when we treat with a single (or very occasionally a second) moderate dose of radioiodine (as reflected in the Gronich et al, 2020 study).
The interpretation of the medical literature on this matter by most thyroid experts is that the risk of cancer developing after radioactive iodine for hyperthyroidism is either non-existent or negligible and if one compares it with the risks of serious side-effects of antithyroid drugs and thyroidectomy, there is little difference.
It may seem paradoxical that despite these reassurances, we ask patients to take precautions such as keeping a distance from other people, but this is based on a the principle that no matter how small / non-existent the risk is, if we can take some simple measures to reduce the exposure of others around us to radioactivity, it is good practice to do so.
We normally advise all patients who are on antithyroid drugs, if they get a sore throat, high temperature, or any other symptoms of infection, to stop taking the antithyroid drugs and get a blood count as a matter of urgency. If the blood count is normal re-start the antithyroid medication.
How easy it will be to implement these actions in the middle of Covid-19 is at present unclear and may differ from place to place, but look out for the BTA/SfE announcement.
Keep safe.
Dr P Perros
Consultant Endocrinologist
Newcastle upon Tyne
Thyroid UK would like to send our thanks to Dr Perros for taking the time out of his busy day to help us all.
Autoimmune thyroiditis and covid-19
Health anxiety and agranulocytosis
Antithyroid Treatment as Effective as RAI for Graves Relapse and better for TED
Thyroid disease and Covid 19 risk
Covid-19, Vaccines and being Hypothyroid
