Hyperthyroidism in Pregnancy

Hyperthyroidism may rarely present as a new diagnosis in pregnancy. However, more common is relapse of previously controlled hyperthyroidism.

Also see our general article on Hyperthyroidism.

• Thyroid gland enlargement
• Increased gland vascularity
• These changes reverse postnatally

• Occurs in 2/1000 pregnancies in UK.
• The commonest cause is Graves' hyperthyroidism - overactivity resulting from the presence of thyrotrophin receptor stimulating antibodies (TRab).
• New onset Graves' hyperthyroidism is estimated to occur in about 0.15% of pregnancies.
• Transient gestational hyperthyroidism may also occur - it has a 2-3% prevalence in Europe, but is much higher in South Asians.

• Associated with hyperemesis gravidarum
• Thought to arise from high levels of hCG
• May occur in molar pregnancy
• The high hCG stimulates the TSH receptor
• Patients are not usually thyrotoxic
• Antithyroid drugs do not help
• Resolves as hCG falls

See general article on Hyperthyroidism for signs and symptoms. However, in pregnancy the following warrant TFTs:

• Tachycardia
• Palpitations
• Heat intolerance
• Systolic murmur
• Bowel disturbance
• Failure to gain weight
• Emotional upset

Features of Graves' disease may also be seen e.g.

• Eye signs
• Tremor
• Weight loss
• Pre-tibial myxoedema

• Some of the symptoms may be due to pregnancy itself
• If tachycardia is present then anaemia, arrhythmias and volume depletion might need to be considered
• More rare causes such as phaeochromocytoma might also need to be considered

• Thyroid function tests (TFTs): Serum TSH can exclude primary thyrotoxicosis. Confirm diagnosis with free T4 levels. If TSH suppressed but free T4 levels normal then, if not previously supplied, need free T3 level (T3 toxicosis occurs in 5% of patients). Previously successfully treated Graves' disease is not associated with abnormal TFTs during pregnancy.³
• Autoantibodies: These are most commonly seen in Graves' disease. These include:
  • Antimicrosomal antibodies - against thyroid peroxidase.
  • Antithyroglobulin antibodies.
  • TRab - important to measure in pregnancy.
• Thyroid USS can be requested but thyroid uptake scans are not recommended.

Poorly controlled hyperthyroidism during pregnancy is associated with the following:

• Pre-eclampsia
• Maternal cardiac failure
• Fetal loss
• Premature labour
• Low birthweight baby
• High miscarriage rate is associated with high thyroid hormone and thyrotrophin hormone levels (i.e. not due to autoimmunity)
• Neonatal hyperthyroidism (see next section)

At present subclinical hyperthyroidism had not been associated with any adverse effects during pregnancy.^1,4,5

• Maternal TRab can decline or alter from stimulatory to inhibitory during pregnancy. Thus there maybe an improvement in hyperthyroidism during pregnancy.
• However, if this does not occur the maternal TRab can cross the placenta and stimulate the neonatal thyroid gland. This leads to neonatal hyperthyroidism.
• Neonates develop the following:
  • Intrauterine growth retardation
  • Tachycardia
  • Heart failure
  • Goitre formation

• Pre-pregnancy planning is advised but benefit not proven.
• Good control of maternal hyperthyroidism is associated with better maternal and fetal outcomes.
• Control is particularly important as the pregnancy progresses, especially in the third trimester. This is the result of suppression of the fetal pituitary thyroid axis from maternal transfer of thyroxine when hyperthyroidism is poorly controlled. Decide which of the following groups the patient belongs to:

Pregnant mothers with Graves' hyperthyroidism already on treatment or completed treatment

• This include those currently on treatment or who have already completed treatment e.g. medications, radioiodine or surgery.
• Measure TRab in first trimester.
• If TRab levels high then need close monitoring of fetus as neonatal hyperthyroidism may occur.
• Monitoring usually involves serial ultrasonography.
• TRab should be re-measured in the 3rd trimester.
• If TRab remains high at 36 weeks then the neonate needs to have TFTs performed after birth and then repeated few days later.

Pregnant mothers with a new diagnosis of hyperthyroidism

• All pregnant women should be referred urgently for assessment of a new diagnosis.

Treatment of all cases of hyperthyroidism during pregnancy (new diagnoses or worsening of previously controlled hyperthyroidism)

• Antithyroid drugs are the first line for all.
• Radioiodine is contraindicated.
• Surgery is only if absolutely necessary and requires patient to be rendered euthyroid with drugs to begin with.
• All cases should be discussed with a specialist.
• This needs to be urgently if adrenergic symptoms are present which may require treatment.
• Adrenergic symptoms can be treated with short courses of beta blockers e.g. propranolol. Use beyond a few weeks may adversely affect the fetus and is not advised.
• Antithyroid drugs:
  • Propylthiouracil may cross the placenta less readily than carbimazole and it is first choice in pregnancy and breast-feeding.^5,7
  • Carbimazole has been associated with teratogenic affects rarely.
  • However, in some countries carbimazole may be the only choice available and the risk of not treating maternal hyperthyroidism will far outweigh those of potential teratogenicity.
  • The aim is to keep the thyroid hormones in the upper third of the reference range. Once this is achieved then the dose of propylthiouracil is decreased to prevent affects on neonatal thyroid function (may produce neonatal hypothyroidism). A similar strategy is used in Graves' disease presenting during pregnancy.
  • Block and replace regimen is not recommended and medications need to continue into labour - albeit at a lower dose.
  • Remember that antithyroid drugs may cause neonatal hypothyroidism - thus minimal dose required should be used and thyroid hormones should be kept with in the upper third of the normal range.
• All monitoring of pregnant women should take place in secondary care but a full TFTs profile should be sent from primary care. Monitoring usually involves the following:^1,5
  • Measure TFTs every 4-6 weeks
  • Serial fetal ultrasonography (looking for intrauterine growth retardation, hydrops fetalis, advanced bone age, goitre, tachycardia and heart failure)
  • Check TRab in first trimester and third trimester (at 36 weeks)

Postpartum¹

• Patients may continue to breast feed - the risk of propylthiouracil and carbimazole being secreted into breast milk is negligible. However, neonatal thyroid function should be checked regularly.
• Measure TFTs in both mother (6 weeks and 3 months) and the neonate (six hours and again a few days later). The reason for rechecking TFTs a few days after birth is that the neonate will have metabolised any maternal antithyroid drugs by this time.

Good thyroid control is associated with a normal pregnancy with good maternal and fetal health.