Radioiodine – a ‘magic bullet’ for treatment of hyperthyroidism. A simple capsule can successfully treat many patients first time with little or no side effects
Head of Radiopharmacy
Sandwell and West Birmingham Hospitals NHS Trust
Targeted therapy using radiopharmaceuticals, in which particle-emitting radionuclides such as 131Iodine are administered to the patient to deliver a radiation dose to selected tissues, is by no means a new concept. 131Iodine has been used for more than 60 years to treat both hyperthyroidism and thyroid cancer. When used in the sodium iodide form, 131Iodine becomes incorporated into the iodine metabolic pathway in the same way as non-radioactive iodine via the sodium/iodide (Na/I) symporter (NIS) (Figure 1).
When first diagnosed, most patients are treated with antithyroid drugs such as carbimazole. For some, a course of antithyroid medication treatment is sufficient and upon withdrawal they need no further treatment. For others, further intervention is required and those patients may then be offered radioiodine as an option. Some may also be offered surgery. However, radioiodine has several advantages over surgery: it is non-invasive and it can be done as an outpatient, for example.
Before treatment, an initial thyroid scan may be performed using either 123I-sodium iodide or 99mTc-sodium pertechnetate to assess and estimate the likely uptake of radioiodine. Using 123I-sodium iodide will give a more accurate measure of thyroid uptake, and in some centres the administered dose of radioiodine may be adjusted to account for this. However, it is expensive and there is limited evidence to show what, if any, impact this has on the outcome of treatment. 99mTc-sodium pertechnetate is a large negatively-charged ion, and as such gets taken up into the thyroid gland via the NIS route. 99m-Tc Pertechnetate is a pure gamma-emitter, which means it is good for imaging but has no therapeutic effect.
Whichever agent is used, performing the uptake scan does not necessarily result in lower remission or hypothyroid rates as the individual response to administered radioiodine varies.[2–4] It does, however, confirm that there is uptake and that any negative feedback on the thyroid stimulating hormone by increased iodine levels in the patient’s blood should not therefore affect uptake of the radioiodine. It also will show if there are any ‘cold spots’ – ie, areas where there is no uptake of the tracer – which could be indicative of thyroid cancer. Should a cold spot be seen, the nuclear medicine consultant may decide to postpone the radioiodine treatment in order to biopsy the gland. It is important that the biopsy be performed before radioiodine treatment as any changes in the cells would be difficult to detect after treatment.
An example of a 99m Tc-sodium pertechnetate thyroid scan can be seen in Figure 2.
This is usually done on the day of treatment, and in most centres is performed using a blood rather than urine test, as pregnancy can be detected slightly earlier. It is essential that all women of child-bearing age, except those who have been sterilised or who are on Depo-Provera, have a pregnancy test before proceeding with the treatment. Even those on the contraceptive pill or with an IUD must have a test. The consequences of administering radioiodine to a pregnant patient are severe, as it crosses the placenta and could adversely affect the development of the baby’s thyroid gland, resulting in cretinism – stunted physical and mental growth as a result of foetal hypothyroidism.
Therefore, female patients are told to ensure that they do not become pregnant for six months after treatment.
There is less evidence to show adverse effects to children fathered by men who have had radioiodine, but they are also asked to avoid fathering a child for four months after treatment. This time period is linked to the time taken for a sperm to develop and mature.
Role of the pharmacist
The radiopharmacist’s role varies in different centres. It may involve simply ordering the isotope. However, in some hospitals the radiopharmacist may undertake the patient counselling role.
Anxiety is common in these patients, and can itself be a symptom of hyperthyroidism. In addition, many patients are understandably anxious about the prospect of being treated with radioactivity. The patients are asked to take some precautions in terms of contact with other people after receiving the therapy, which may also increase their anxiety levels. It is therefore important to reassure the patients whilst still giving them all the required information. Patient counselling must cover the following points:
1. An explanation of what hyperthyroidism is, including the role the thyroid gland plays, is required.
2. Treatment options. This is required in order for the patient to give informed consent to the treatment.
3. How radioiodine works to treat hyperthyroidism.
4. 131Iodine emits gamma rays as well as the beta particles which have the therapeutic effect. Beta particles do not usually pose a significant radiation protection problem to others, as they cannot travel very far and often are absorbed by the patient’s own body to a great extent. Gamma rays, although having no therapeutic effect, easily travel through the patient’s body and can therefore give a radiation dose to other people, although they do not directly harm them. This gives rise to significant radiation protection challenges. Once the patient has taken the radioiodine capsule, the radioactivity will be contained within his or her body and as such, he or she then becomes a ‘radioactive source’. All exposures to radiation must be assessed by looking at risks and benefits and for the patient, the exposure has the benefit of treating the hyperthyroidism. For other people, there is no benefit, so the patient is asked to limit his or her exposure. There are specific time limits which advise avoiding prolonged close contact which are based on measured radiation doses to other people. Maintaining time limits for avoiding contact with adults and children, and for returning to work must therefore be explained. The recommended limits are found in Table 1.
5. Confirmation that any anti-thyroid medication has been stopped and if and when it should be restarted. Carbimazole, for example, should be withdrawn a minimum of two days prior to treatment, with the usual time frame being five days prior to treatment. Many departments stop Propylthiouracil two to seven days before treatment. Data on the cessation duration is conflicting, and there is some evidence that medication continues to exert an effect for up to two weeks and is thought to have a radioprotective action on the thyroid. A larger dose of radioiodine may be used in some centres to counteract this. Propranolol may be given at a dose of 20–40mg three times a day for the alleviation of cardiac symptoms. This does not need to be stopped prior to radioiodine treatment.
6. Warning of the possibility of thyroid storm (a transient worsening of the hyperthyroid symptoms). This is rare, but if it does occur, it tends to start about two days after treatment and may continue for up to a week. In the event of this happening, the patient is advised to rest and to contact his or her doctor if he or she is concerned.
7. Check if he or she have taken any other medication or eaten any food which could interfere with the uptake of the radioiodine. Some types of fish may affect uptake if they contain a lot of iodine. Compounds containing iodine such as amiodarone and some radiographic contrast agents may block uptake for up to one year after cessation of treatment.
8. Since the percentage uptake of iodine will vary in different patients, it is difficult to predict the outcome accurately. There is a possibility that one treatment may not be sufficient, and a small percentage of patients will need a repeat dose. There is also the possibility of becoming hypothyroid. Fifty to 75% of patients would be rendered euthyroid within six to eight weeks. Again, some reassurance may be required.
9. Explain the treatment for hypothyroidism (ie, thyroxine), including that it would be life-long.
10. Explain that there is some evidence of worsening thyroid eye disease (exopthalmus) after treatment[2,8] though there are other risk factors which can affect this such as smoking or early treatment with thyroxine. Should the patient show signs of thyroid eye disease, treatment with prednisolone whilst having the radioiodine treatment may prevent this.
11. Since the radioiodine is largely excreted via the urine, good hygiene is important. Patients are asked to take particular care with hand-washing after going to the toilet, and must be careful to clean up any spills thoroughly. The length of time depends upon the administered dose and the individual patient.
12. As already mentioned, the patient must avoid pregnancy for six months, or fathering any children for a four-month period post therapy.
13. In the unlikely event that any patient is breastfeeding, this must be discontinued permanently.
14. Airports and many ferry terminals now have very sensitive radiation detectors, and for at least four months after treatment the patient may set off the alarms.
The patient must be given an information sheet containing a summary of the precautions to be taken after receiving treatment, as well as a contact number should he or she have any problems. The patient must sign a consent form to state he or she understands all the advice provided and that she is not pregnant or breastfeeding.
Before administration can occur, the nuclear medicine consultant must authorise the treatment. If the patient is happy to proceed, the dose is administered in capsule or liquid form. There is less likelihood of spillage and subsequent radiation decontamination and protection problems with a capsule. However, there are no means of adjusting the dose with a capsule, so this would not be suitable for a ‘one-stop’ clinic where the patient has a 123I uptake scan and subsequent dose calculation and administration on the same day.
Any member of staff involved in the explanation of the procedure, calibration of the activity or the equipment used to measure the activity, confirming the patient is a suitable candidate for treatment, prescribing or administering the capsule is considered an ‘operator’ under Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER) and must therefore receive appropriate recorded training.
1. HP Rang/MM Dale, Pharmacology 1st Edition. Page 370.
2. Clinical Guidelines; Report of a Working Party 2007 for the Royal College of Physicians.
3. Jarløv et al. Clin Endocrinol (Oxf) 1995;43(3):325–29.
4. Leslie et al. J Clin Endocrinol Metab 2003;88(3):978–83.
5. Textbook of radiopharmacy, 3rd Edition. Chapter 29, page 373. Edited by Charles B. Sampson
6. Medical and Dental Guidance Notes. Edited by Penny Allisey-Roberts. Published by the Institute of Physics and Engineering in Medicine, 2002
7. Ming-der et al. J Nucl Med 2003;44(5):832–38.
8. Sridama V and DeGroot L. Am J Med 1989;87:70–73.
9. ARSAC Notes for Guidance.