Management of hyperthyroidism during pregnancy; data from a large primary care cohort

Dr Peter Taylor, Welsh Clinical Academic Trainee, Cardiff University and Dr Bijay Vaidya, Consultant in General Medicine, Diabetes and Endocrinology, Royal Devon and Exeter Hospital

Introduction

It is well known that abnormal thyroid function in women who are pregnant is associated with increased risk of miscarriage, problems with delivery and may impair offspring development. Whilst it is well established that pathological thyroid dysfunction is associated with adverse outcomes, we are now becoming aware that even minor variation in thyroid status within the normal population range has key health implications particularly in pregnancy.

Hyperthyroidism (thyroid overactivity), usually due to Graves' disease is a relatively common disorder in pregnancy, affecting about 1 in 500 pregnant women. Data on whether hyperthyroidism in pregnancy is optimally managed in the UK and outcomes of the pregnancies associated with hyperthyroidism are lacking and studies have been relatively small in size to date. In particular there are concerns regarding the adequacy of current treatment in terms of control of thyroid status, with subsequent increased risk of adverse pregnancy outcomes including miscarriage and need for an emergency Caesarean section. Furthermore there is concern over which anti-thyroid drug is safest to use in pregnancy. Current guidelines recommend propylthiouracil as the preferred antithyroid drug in early pregnancy as carbimazole is associated with congenital abnormalities. However recent data has led to concerns over propylthiouracil use as it can cause liver failure and its use has now also been associated with congenital abnormalities. The guidelines have suggested that using propylthiouracil in the first trimester and switching over to carbimazole afterwards might provide the lowest risk of adverse outcomes, however this has not been studied and there are concerns regarding whether this switch results in a deterioration of hyperthyroidism. Taken together there is a pressing need to examine this important topic and identify where current management could be improved.

We propose to analyse a large primary care database totalling over 17,000 people with hyperthyroidism to identify the risks and benefits of current practice and identify where management might be improved. We will identify whether treatment targets are being routinely met and the degree of harm (such as miscarriage) arising from failure to achieve these. Furthermore we will be able to study for other adverse obstetric outcomes (e.g. need for emergency Caesarean section) and adverse offspring outcomes (e.g. congenital abnormalities) by treatment adequacy and also for carbimazole and propylthiouracil. This will enable us to inform both patients and clinicians of best practice for instance with regard to management of hyperthyroidism in pregnancy and reducing the risk of adverse outcomes. A key advantage of the nature of this research is that data has already been collected allowing rapid analysis of results as conventional studies would take years to acquire this data and data are needed in this area urgently. Furthermore we both have substantial expertise in analysing this database and have published several research studies relating to thyroid disorders in pregnancy.

Final report to follow.