The most common thyroid diseases during pregnancy are hyperthyroidism and hypothyroidism.
Hyperthyroidism
Hyperthyroidism refers to the excessive production of thyroid hormones by the thyroid gland, resulting in increased excitability of the nervous, circulatory, and digestive systems, as well as heightened metabolism. The condition is influenced by pregnancy-related physiological changes, and its diagnosis and treatment during pregnancy differ from that outside of pregnancy.
Mutual Effects of Pregnancy and Hyperthyroidism
Thyroid hormone secretion is significantly influenced by pregnancy. Human chorionic gonadotropin (hCG) secreted by the placenta has a similar alpha subunit to thyroid-stimulating hormone (TSH) and can stimulate the thyroid gland, leading to decreased TSH levels in the serum and increased serum total thyroxine (TT4) and total triiodothyronine (TT3). Pregnant individuals with severe or poorly controlled hyperthyroidism are at increased risk of miscarriage, preterm birth, fetal growth restriction, fetal hypothyroidism, and fetal goiter. Poorly managed or untreated hyperthyroidism during labor or surgery, due to stress, infections, or inappropriate discontinuation of medication, may trigger a thyroid storm.
Clinical Manifestations
Hyperthyroidism during pregnancy includes cases diagnosed before pregnancy and newly diagnosed cases during pregnancy. The symptoms are similar to those in non-pregnant individuals, presenting with hypermetabolism, irritability, heat intolerance, excessive sweating, facial flushing, tachycardia, and widened pulse pressure (> 50 mmHg). Physical examination may reveal increased skin temperature, exophthalmos, hand tremors, and more severe symptoms such as arrhythmias and cardiac enlargement. Laboratory findings typically include suppressed TSH levels and elevated free T4 (FT4) or total T4 (TT4).
The diagnosis of a thyroid storm is considered when symptoms such as life-threatening fever, cardiovascular dysfunction, or altered mental state occur alongside biochemical evidence of hyperthyroidism. Suspicion of a thyroid storm warrants assessment of thyroid function. Possible symptoms include high fever (temperature > 39°C), tachycardia (heart rate > 130 bpm), restlessness, nausea, vomiting, diarrhea, jaundice, and more severe complications such as hypotension, atrial fibrillation, shock, seizures, or coma. Diagnosis is often supported using the Burch-Wartofsky Point Scale (BWPS) for thyroid storm. Common triggers include infections, trauma, surgery, or delivery. The mortality rate among pregnant individuals is high without prompt management.
Diagnosis
Diagnosis is often based on symptoms such as high metabolic activity, symmetrical diffuse thyroid gland enlargement, and exophthalmos, combined with laboratory findings. During early pregnancy, transient gestational hyperthyroidism (GTT) is considered if TSH is suppressed with elevated FT4 levels, especially in cases of severe nausea and vomiting, after excluding persistent hyperthyroidism.
Management
Preconception Management in Hyperthyroidism Patients
A stable and euthyroid state is recommended before conception. Treatment with radioactive iodine (131I) can affect the fetus, and at least six months are recommended between 131I therapy and conception.
Management of Hyperthyroidism During Pregnancy
GTT typically does not require treatment. For pregnancy complicated by hyperthyroidism, the management principles aim to control the progression of the disease while ensuring normal fetal development and a safe pregnancy and delivery period. Medication is the preferred treatment during pregnancy. Propylthiouracil (PTU) and methimazole (MMI) are considered first-line antithyroid drugs during pregnancy, with PTU being the preferred option before 12 weeks of gestation.
- Dosage: PTU at 100–150 mg per dose, administered three times daily; MMI at 10–20 mg per dose, administered twice daily.
Surgical options, such as partial thyroidectomy, may be considered during the second trimester for individuals who do not respond to medication or are allergic to antithyroid drugs.
The use of radioactive iodine (131I) is contraindicated for both diagnosis and treatment during pregnancy.
Obstetric Management
During Pregnancy
Enhanced monitoring is necessary, with both obstetricians and endocrinologists collaboratively managing and monitoring the condition.
During Labor
Vaginal delivery is generally preferred, with attention given to postpartum complications such as thyroid storm and hemorrhage, and proactive measures for complication prevention.
For the Neonate
Assessment is conducted for symptoms or signs of hyperthyroidism or hypothyroidism.
Postpartum and Breastfeeding
Antithyroid medications remain necessary in the postpartum period, with methimazole being the preferred drug during breastfeeding.
Hypothyroidism
Hypothyroidism refers to an endocrine disorder characterized by reduced synthesis and secretion of thyroid hormones or diminished tissue responsiveness to them, leading to decreased systemic metabolism. It can be categorized into overt hypothyroidism and subclinical hypothyroidism (SCH).
Effects on the Mother and Fetus
Untreated hypothyroidism is a significant factor contributing to adverse pregnancy outcomes.
Effects on Pregnant Individuals
Hypothyroidism during pregnancy is associated with an increased risk of obstetric complications in both early and late stages, such as preeclampsia, placental abruption, and heart failure.
Effects on Perinatal Outcomes
In cases of untreated hypothyroidism during pregnancy, there is an elevated risk of complications including miscarriage, fetal growth restriction, and developmental delays such as intellectual disabilities in the fetus.
Clinical Manifestations
Common clinical features include generalized fatigue, lethargy, memory impairment, reduced appetite, hoarseness, constipation, slow speech, sluggishness, expressionless face, thinning hair, dry skin, and low body temperature. Severe cases may involve cardiac enlargement, pericardial effusion, bradycardia, and delayed deep tendon reflexes.
Diagnosis
Hypothyroidism during pregnancy includes cases with a pre-existing diagnosis as well as those newly identified during pregnancy. Early screening is recommended for individuals with high-risk factors, including:
- A history of thyroid hormone replacement therapy before pregnancy.
- A history of hyperthyroidism, hypothyroidism, postpartum thyroiditis, partial thyroidectomy, or radioactive iodine therapy (131I).
- A family history of thyroid disorders.
- Evidence of thyroid autoantibodies.
- Presence of goiter.
- Symptoms or signs suggestive of hypothyroidism.
- A history of type 1 diabetes mellitus.
- Coexisting autoimmune diseases.
- A history of cervical discomfort.
Women with infertility are also recommended to undergo TSH testing to exclude hypothyroidism.
The diagnosis of overt or subclinical hypothyroidism is based on trimester-specific reference ranges for TSH and FT4 levels.
- Overt Hypothyroidism: TSH levels exceed the upper limit of the pregnancy-specific reference range, and FT4 levels fall below the lower limit. When pregnancy-specific reference ranges are unavailable, a 22% reduction in the upper limit of the general population TSH reference range or a threshold of TSH > 4.0 mIU/L combined with clinical symptoms can be used for diagnosis.
- Subclinical Hypothyroidism: TSH levels exceed the upper limit of the pregnancy-specific reference range, while FT4 levels remain normal.
- Isolated Hypothyroxinemia: Characterized by normal TSH levels and reduced FT4 levels.
Management
The treatment goal is to maintain TSH levels in the lower half of the pregnancy-specific reference range. In the absence of trimester-specific reference ranges, TSH levels are generally maintained below 2.5 mIU/L. Collaborative management with an internist is often required. The primary treatment is levothyroxine (LT4).
Preconception Management
Women of childbearing age with a history of hypothyroidism should adjust LT4 dosage to achieve normal TSH levels, ideally less than 2.5 mIU/L, before attempting pregnancy.
Management of Overt Hypothyroidism During Pregnancy
Individuals with pre-existing hypothyroidism receiving LT4 therapy typically require an increase in LT4 dosage by 30%–50% after conception. The medication dosage should be adjusted based on thyroid function tests to maintain TSH levels in the following ranges:
- First trimester: 0.1–2.5 mIU/L.
- Second trimester: 0.2–3.0 mIU/L.
- Third trimester: 0.3–3.0 mIU/L.
Thyroid function should be monitored every four weeks until 28 weeks of gestation and at least once between 28 and 32 weeks.
Management of Subclinical Hypothyroidism During Pregnancy
There is no consensus on whether treatment is necessary for pregnant individuals with SCH. Assessing thyroid peroxidase antibody (TPOAb) status is recommended for all pregnant individuals with elevated TSH levels. Decisions regarding LT4 therapy are based on the degree of TSH elevation as well as the presence of TPOAb. For those receiving LT4 intervention, thyroid function should be monitored every four weeks up to 28 weeks of gestation and at least once between 28 and 32 weeks.
Management of Isolated Hypothyroxinemia
LT4 therapy is not currently recommended for individuals with isolated hypothyroxinemia.
Postpartum Management
LT4 therapy can be discontinued postpartum, regardless of TPOAb status, but serum TSH levels should be reassessed six weeks postpartum.
Additional Care During Pregnancy
Nutritional guidance during pregnancy, fetal growth monitoring, and enhanced antenatal and intrapartum fetal surveillance are crucial. Fetal distress detection should be prioritized. Vaginal delivery is often encouraged in the absence of other obstetric contraindications, with attention to preventing postpartum hemorrhage and puerperal infections.
Neonatal Monitoring
Thyroid function tests, including TSH and FT4/TT4, are recommended for neonates. Neonatal hypothyroidism, if diagnosed, requires immediate LT4 therapy, generally continued for 2–3 years.