Dr Rebecca Scott and Professor Kevin Shotliff advise how GPs can support perinatal women with thyroid disorders in the latest in our complicated pregnancy clinic series
Pre-existing thyroid disorders are commonly seen in pregnant women, with 1-2% of pregnancies occurring in women with hypothyroidism, and 0.2% of pregnancies in women with known hyperthyroidism. New diagnoses of thyroid disease does happen in pregnancy, but is rare (about 0.1% of pregnancies).
Since thyroid hormone crosses the placenta, any imbalance can affect the neurological development of the fetus.
What complicates the management of these disorders further are the normal physiological changes to the thyroid axis in pregnancy that make the non-pregnant reference ranges for thyroid hormone inaccurate. Instead, trimester-specific reference ranges for thyroid hormones should be used.
GPs are experienced at managing hypothyroidism outside of pregnancy, and are usually responsible for pre-pregnancy optimisation in these cases. A pre-pregnancy TSH of less than 2.5iU/l should be the target in women with known underactive thyroid.
In those patients on levothyroxine who are trying to conceive, TSH levels should be checked every 6 months to ensure it remains in the target range. Levothyroxine is the only medication recommended for the treatment of hypothyroidism as it crosses the placenta to be used in fetal development; women on other forms of thyroid replacement medication, such as T3 / lio-thyronine and NDT / natural dessicated thyroid therapies, should be counselled that it is not recommended in pregnancy, and referred to secondary care to discuss transitioning to levothyroxine.
Importance of trimester-specific ranges
The levels of TSH, free T4, and free T3 fluctuate significantly in each trimester of a healthy pregnancy. We typically see a fall in TSH In the first trimester which then rises, while fT4 falls towards the end of pregnancy. Therefore, trimester-specific reference ranges for thyroid function should be used for accurate management, and ideally ranges produced on the local assay platform and relevant to the local population. In the absence of local trimester-specific reference ranges a TSH between the lower end of the reference range and 4mIU/l in each trimester is likely to be safe.
Women with a diagnosis of hyperthyroidism should have their pre-conception counselling and on-going management in secondary care. The goal is to keep their TSH levels at the lower end of the reference range using the lowest possible medication dose. Our local assay has a non-pregnancy normal range of 0.27 – 4.2 mIU/l and our target is 0.27 – 2.0 mIU/l within that range.
Both carbimazole and propylthiouracil, along with an overactive thyroid itself, have been associated with birth defects. It is therefore vital that patients and doctors weigh the pros and cons and make a joint decision about treatment. MHRA advice states that women taking carbimazole should use effective birth control due to an increased risk of congenital malformations, particularly if used during the first trimester. Women who undergo radio-iodine therapy for an overactive thyroid should also avoid becoming pregnant for the first six months post-treatment.
Managing early pregnancy and hypothyroidism
Ideally, thyroid function tests should be checked as soon as a woman on thyroid hormone replacement confirms she is pregnant. If her TSH is outside the trimester-specific range, levothyroxine dose can be adjusted in primary care. However, if there will be a delay in checking thyroid function, or if women have inadequate thyroid replacement prior to pregnancy, women should be advised to empirically increase their levothyroxine dose by 25% until the TSH can be checked.
Thyroid antibodies and pregnancy
Thyroid peroxidase antibodies have been associated with increased miscarriage risk. However there is no treatment that reduces the risk of miscarriage in women who are euthyroid but have thyroid antibodies. Therefore, testing for these antibodies is not recommended.
Monitoring known thyroid disease in pregnancy
In women with an underactive thyroid and on a stable dose of levothyroxine, thyroid function should be checked once per trimester in primary care, and levothyroxine adjusted if required. If the levothyroxine dose is changed at any point, thyroid function should be repeated after 4 weeks. This can occur in primary or secondary care, depending on local pathways.
Women with an overactive thyroid should have their thyroid function and medication managed by an antenatal endocrine service during their pregnancy. Women with hyperthyroidism may require extra growth scans and monitoring of the fetal heart rate. Women with hypothyroidism do not require extra fetal monitoring in pregnancy.
What is isolated hypothyroxinaemia?
Isolated Hypothyroxinaemia is a condition where TSH levels are normal, but free T4 levels are low. Risk factors include high BMI and iodine deficiency. It is associated with mild cognitive impairment in children. However, treating with levothyroxine does not improve fetal outcomes, and can lead to maternal side effects, so treatment is not recommended
Thyroid dysfunction diagnosed during pregnancy
If hypothyroidism is diagnosed during pregnancy, treatment with levothyroxine, typically starting at a 50mcg daily dose, should be initiated.
Gestational thyrotoxicosis (GT) is quite common, affecting up to 3% of pregnancies. It usually presents with suppressed TSH levels and is often associated with severe morning sickness (hyperemesis). The hormone beta-HCG, produced by the placenta at rapidly increasing amounts in early pregnancy, has a similar structure to TSH and can mildly activate the thyroid, in turn causing TSH suppression.
The other features of hyperthyroidism – palpitations, sweating, weight loss – are not generally seen in GT. GT requires symptomatic management, often with antiemetics and beta-blockers, and the TSH typically returns to the normal range by the second trimester. Women diagnosed with GT need to have their thyroid function rechecked 4 weeks after the initial test. However, if there is a suspicion that the overactive thyroid is due to Graves’ disease or a toxic nodule, an urgent referral to the endocrine team is needed.
Postnatal management and monitoring
Infants born to women with hyperthyroidism will need thyroid function testing within the first 5-14 days due to the risk of neonatal thyrotoxicosis. This should be done in secondary care. Babies born to women with hypothyroidism require no additional investigations in addition to the check for congenital hypothyroidism on the Guthrie test.
All women with thyroid dysfunction should have their thyroid function checked 6 weeks’ post-partum. Women who required an increase in levothyroxine in pregnancy may be able to reduce to their pre-pregnancy dose. Further monitoring should take place at the same frequency as pre-pregnancy monitoring. Women with hyperthyroidism should have their thyroid function and medication monitored by secondary care post-partum.
Women who were started on levothyroxine by their fertility team, and did not have documented hypothyroidism prior to pregnancy or fertility treatment, should stop the levothyroxine entirely after childbirth. They should have a repeat thyroid function check 4 weeks later. Treatment should then only be offered as per non-pregnancy guidelines.
Post-partum thyroiditis affects 5-10% of women within the first year after delivery or miscarriage. It is more prevalent in women with known autoimmune disorders or those who are positive for thyroid antibodies. It usually starts with a temporary overactive thyroid phase, followed by an underactive thyroid phase 4-6 months post-pregnancy. Symptoms can be vague, such as fatigue, and sometimes resemble post-partum depression. Thus, if a woman presents with these symptoms within the first year post-partum, her thyroid function should be checked.
Dr Rebecca Scott is consultant in diabetes & endocrinology and consultant in obstetric medicine and Professor Kevin Shotliff is consultant physician at Chelsea and Westminster Hospital in London.
Alexander EK et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.
Thyroid 2017; 27(3),315-389
MHRA Drug Safety Update: Carbimazole: increased risk of congenital malformations; strengthened advice on contraception, February 2019