A randomised study of two anti-thyroid drug treatment regimens in young people with thyrotoxicosis

Dr Tim Cheetham, University of Newcastle upon Tyne

Final report

Around 120 young people (under the age of 16 years) present with thyrotoxicosis (an overactive thyroid gland) every year. Most will be treated initially with anti-thyroid drugs (usually Carbimazole, occasionally Propylthiouracil).

Anti-thyroid drugs (ATD) can be used in one of two main ways:

  • 'Block and replace' treatment (BR). This is where thyroid hormone production by the over-active thyroid gland is switched off completely by ATD and thyroxine is then added in a 'replacement' dose.
  • 'Dose titration' treatment (DT). This is where the dose of ATD is adjusted so that hormone production by the overactive gland is reduced to normal.

Both BR and DT therapy have potential advantages and disadvantages. Potential advantages of the BR approach include:

  • More stable thyroid function tests.
  • A reduced number of blood tests and visits to hospital.
  • A reduced likelihood of the over-activity returning when the ATD is stopped.

Potential advantages of the DT approach include:

  • Fewer side effects with a lower ATD.
  • Improved compliance on one rather than two medications because the DT approach involves taking just ATD and not thyroxine as well.

A recent study suggested that DT was probably best in adults although some adult physicians feel that there are still very good reasons to use BR. A particular consideration in the young person is the fact that they are growing and developing and it may be that more stable blood tests are particularly desirable at this time of life. Hence the BR approach may prove to be the preferred option in the young.

A study looking at the two approaches has been underway in the UK for three years and a number of centres are already taking part including: Birmingham, Cambridge, Edinburgh, Glasgow, Oxford and Newcastle. A number of factors are being looked at as part of the study including the likelihood of the over-activity persisting in the long term, how often thyroid function tests are normal and the frequency of side-effects. We are also collecting blood from the young person and their parents to look at some of the genetic factors that might affect whether someone gets the thyroid problem in the first place.

Patients in recruiting centres are given the option of taking part in the study, which doesn't involve extra blood tests, or extra visits to hospital. We have recruited 30 subjects to date but require 160 and we need to employ someone to work for several hours each week on the study. This person will be responsible for helping centres to recruit patients, helping with administrative aspects of the study and for data entry. This is an important stage of the study and the appointed person will help to ensure that the required numbers of patients are recruited. This funding from the British Thyroid Foundation will also facilitate adoption by the Medicines for Children Research Network, which will also help to boost recruitment.

Learning how best to use anti-thyroid drugs is very important because it will provide families and health-care professionals with information about short and longer-term outcome, which they can use when making a decision about treatment.

This study has been looking at how best to use anti-thyroid drugs in young people with an overactive thyroid gland. It is trying to establish what the advantages and disadvantages of the ‘block and replace’ and ‘dose titration’ approaches are in this age group.

We are delighted to say that the research award from the BTF has had a major beneficial impact on the progress of the study. The money has been used to pay for the time of a trial co-ordinator and data manager who has been able to strengthen and develop the study in a number of different ways including:

  • Bringing the trial forms up to date, both at a local (Newcastle) and national level.
  • Involving more centres. Further paediatric endocrine units around the country are now in a position to recruit patients to the study. Units that are able to recruit to the study (or are very close to being able to recruit) include Aberdeen, Birmingham, Cambridge, Cardiff, Coventry, Edinburgh, Glasgow, Liverpool, Manchester, Norwich and Newcastle.
  • Raising the profile of the study at national level which has resulted in further financial and administrative support from the NHS research ‘infrastructure’.

The study team are extremely grateful for the support of the BTF and we are hopeful that we can recruit the necessary patients over the course of the next three years.