Hyperthyroidism (hyperthyroidism) is a common disease of the endocrine system that occurs in women between the ages of 20 and 50. Grave’s disease accounts for more than 80-85% of all hyperthyroidism and is an autoimmune disease. Hyperthyroidism can lead to menstrual disorders such as reduced menstruation in women of childbearing age, affecting ovulation and decreasing the rate of conception, but most patients can conceive with good pregnancy outcome after thyroid function is stabilized through treatment. Some patients with hyperthyroidism who become pregnant before their thyroid function is controlled, or whose pregnancy increases their psychological and physiological burden, or who do not take medication for fear that it will affect the fetus, or who do not take enough medication, may cause pregnancy complications such as preterm labor, miscarriage, low birth weight babies, congenital malformations, increased risk of hypertension during pregnancy, or even induce thyroid crisis, which may endanger the life of the mother and child. The risk of thyroid crisis can even be induced, endangering the lives of both mother and child. Many studies have shown that continuous monitoring and treatment before and during pregnancy and timely control of hyperthyroidism can significantly reduce the above complications, which is especially important for the treatment of hyperthyroidism in pregnancy.
1. Diagnosis.
The diagnosis of combined hyperthyroidism in pregnancy has its own special features. First, hyperthyroidism in pregnancy should be differentiated from transient thyrotoxicosis of pregnancy (GTT). Many pregnant women do not have hyperthyroidism before pregnancy, but during early pregnancy they may show some manifestations similar to hyperthyroidism, such as vomiting, increased appetite, excessive sweating, and panic attacks; laboratory tests show mild increases in TT3 and TT4 and slight decreases in serum TSH (especially in the first trimester) but negative thyroid hormone receptor antibodies. These changes are related to the increase in HCG and estrogen during pregnancy, and are normal physiological changes that usually return to normal in the middle and end of pregnancy or after delivery without treatment.
When hyperthyroidism is combined with pregnancy, the diagnosis is not difficult if there is a history of hyperthyroidism before pregnancy. In the case of hyperthyroidism in pregnancy, a slight decrease in TSH (O.1-0.5 mU/L) is not diagnostic of hyperthyroidism or subclinical hyperthyroidism. The diagnosis of hyperthyroidism in pregnancy is not based on uniform criteria, but the diagnosis of hyperthyroidism in pregnancy should be more relaxed than that of hyperthyroidism in non-pregnancy: increase in serum free T3 (FT3) and free T4 (FT4) beyond 10% of the normal index, TSH below 0.1 mU/L. Ophthalmic signs, significant goiter and positive thyroid hormone receptor antibodies (TRAB) are helpful for differential diagnosis.
2. Treatment.
The natural course of hyperthyroidism during pregnancy is an early exacerbation with late remission and easy recurrence after delivery. This is because in the second six months of pregnancy, the pregnancy is in a state of immunosuppression and the dose of ATD needed may be reduced. After delivery, the immunosuppression is lifted, hyperthyroidism is likely to recur, and the need for ATD may increase. To address this feature, our strategy for treating hyperthyroidism in pregnancy is to treat it early and to continue treatment during pregnancy and after delivery. The thyroid gland is immature in the first 3 months of life and is completely dependent on the mother’s thyroid hormones. Patients must understand the importance of early treatment, especially during the first trimester, to reduce maternal thyroid function to normal or almost normal. The reasons for this are untreated or late treatment of hyperthyroidism and inappropriate treatment. Some patients with hyperthyroidism combined with pregnancy overemphasize the adverse effects of ATD and believe that it is a medicine with three toxins, or even refuse to take any medicine, resulting in uncontrolled hyperthyroidism and serious consequences such as severe gestational hypertension, heart failure, hyperthyroid crisis, stillbirth and maternal death. Recent studies have concluded that the continued use of maintenance doses of antithyroid drugs during pregnancy after the condition has been controlled can effectively prevent the recurrence or exacerbation of postpartum hyperthyroidism without increasing the incidence of neonatal hypothyroidism or malformations.
For patients with hyperthyroidism in pregnancy, there are two main types of treatment: oral antithyroid drug (ATD) therapy and surgical treatment.
(1) The choice of oral antithyroid drugs (ATD).
There are two main types of common clinical thyroid medications: methimazole and propylthiouracil (PTU). Since ATD can affect fetal thyroid function through the placenta, small doses of ATD should be used as much as possible to achieve control of hyperthyroidism. Propylthiouracil (PTU) is recommended as the first choice for hyperthyroidism in pregnancy because of its short half-life (60 min), low entry into the placenta and breast milk, and less likely to cause fetal or neonatal hypothyroidism; the initial dose of PTU is 300 mg/L, and the maintenance dose of 50-150 mg/d is safe for the fetus. In fact, it is reasonable to adjust methimazole to PTU even after the patient is informed of the pregnancy. Domestic and international studies have even shown that the safety of methimazole and PTU application during pregnancy is comparable and does not increase the incidence of fetal malformations and abnormalities. Patients should have their thyroid function tested regularly (usually monitoring thyroid function, blood routine and liver function once a month). Since pregnant women themselves have elevated thyroid hormones, the target value of thyroid hormones can be relaxed to within 10% of the normal index.
(2) Surgical treatment
For individual patients whose condition cannot be satisfactorily controlled by medication and who wish to continue pregnancy, or for patients with allergy to antithyroid medication or leukopenia, surgical treatment can be selected for close observation until the middle of pregnancy (4-6 months). Surgery in early or late pregnancy is likely to cause miscarriage or preterm delivery.
(3) Breastfeeding
Many women taking ATD are afraid to breastfeed their infants for fear that the drug will pass into breast milk. The amount of methimazole entering the breast milk is 0.1% to 0.17% of the oral dose, while PTU is only 0.0%, so PTU should be preferred. The best way to take PTU is to take it immediately after breastfeeding and then breastfeed after an interval of more than 3 to 4 hours. PTU 300 mg/d is generally considered to be safe for the nursing fetus. If the mother takes 200 mg of PTU 3 times a day, the amount of PTU transferred from the mother’s milk to the infant is 149 mg per day, and if the infant weighs 4 kg, the intake is equivalent to 3 mg of PTU for a 70 kg adult, which is equivalent to 1/17 tablets of PTU. A recent 7-year prospective follow-up study showed that women with hyperthyroidism who were breastfeeding on PTU or methimazole had no adverse effects on thyroid function in the next generation and no difference in IQ from children of the same age. The American Academy of Pediatrics has concluded that both PTU and methimazole are suitable for use during lactation.
3. Precautions
(1) Patients with controlled hyperthyroidism can become pregnant. Generally speaking, after the dose of oral medication is reduced to an appropriate dose (e.g., methimazole is reduced to 10 mg) and thyroid function is under control, the patient can prepare for pregnancy. Many patients and even doctors believe that pregnancy is not advisable when hyperthyroidism is present, and that pregnancy should only occur after treatment has been stabilized and then discontinued for 1 year on ATD1. Many patients have terminated their pregnancies on the advice of their doctors due to concerns about their risks, and some patients have had multiple pedestrian abortions. In fact, this is not advocated abroad at all, and abortion is only considered for those who are not controlled by treatment.
(2) The addition of levothyroxine tablets (L-T4, e.g., eugenol) to anti-thyroid medication is not recommended. In the past, it was advocated to add L-T4 to prevent hypothyroidism, but since L-T4 can hardly pass through the placenta and cannot prevent fetal hypothyroidism and postpartum recurrence, but will increase the mother’s ATD dosage, which is unfavorable to the fetus, L-T4 is generally not added.
(3) Be careful with β-blockers: some scholars believe that these drugs can pass through the placenta, increase the sensitivity of the uterus and make the uterus contract continuously, which may cause fetal growth restriction, bradycardia and the risk of intrauterine asphyxia, so the combined use of β-blockers is not advocated.
(4) Forbidden to eat seaweed, nori, seafood and other iodine-rich foods, and prohibited isotope I131 treatment. Excess iodine can aggravate and prolong the course of the disease, and patients with hyperthyroidism should limit iodine intake. Isotope I131 treatment can cause goiter and hypothyroidism in newborns, and radioisotope I131 treatment is not recommended during pregnancy. If a female patient has been treated with isotope I131, pregnancy should be allowed only after six months of discontinuation of the drug.
(5) Pregnant women with hyperthyroidism should be followed up regularly in outpatient clinics to enhance fetal monitoring and prenatal care. Regular fetal ultrasound examination is recommended, and fetal heart monitoring should be performed in late pregnancy, and admission to hospital for monitoring of labor at 37-38 weeks of pregnancy is recommended. At the same time, we should strengthen nutrition, pay attention to rest, avoid mental stimulation and mood swings during pregnancy, and pay special attention to the presence of oedema, elevated blood pressure, urine protein and other signs of hyperemesis gravidarum. Choose the delivery method according to the specific situation and the obstetrician’s recommendation, and pay attention to prevent the occurrence of hyperthyroidism crisis during delivery. The chance of cesarean section in combined pregnancy with hyperthyroidism can be 30%, and 35.54% in China.
(6) When newborns are born, cord blood is routinely left to check thyroid function and related antibodies. Occasionally, severe unremitting cases require treatment.