Hyperthyroidism (hyperthyroidism) is a common endocrine disorder caused by the overproduction of thyroid hormones. Women with hyperthyroidism often present with disrupted, reduced or amenorrheic menstruation and low fertility. However, many women with treated or untreated hyperthyroidism become pregnant, and the incidence is about 1:1000 to 2500 pregnancies. The majority of hyperthyroidism in pregnancy is Graves’ disease, which is caused mainly by autoimmune and psychological stimuli, characterized by diffuse goiter and proptosis.
Clinical manifestations]
Normal pregnancy resembles the clinical manifestations of hyperthyroidism in many ways due to changes in maternal thyroid morphology and function, such as tachycardia, increased cardiac output, enlarged thyroid gland, warm skin, excessive sweating, feverishness, and hyperphagia, which are common in both pregnancy and hyperthyroidism.
Mild hyperthyroidism has no significant effect on pregnancy, but moderate and severe hyperthyroidism, as well as those with uncontrolled symptoms, have increased rates of miscarriage, hyperemesis, preterm delivery, small term infants, and perinatal mortality. The cause of the effect of hyperthyroidism on pregnancy is unknown, but it may be due to the excessive depletion of nutrients caused by hyperthyroidism and the high incidence of hyperemesis, which affects placental function.
During pregnancy, only a small amount of T3 and T4 can cross the placenta because of the placental barrier, so it does not cause hyperthyroidism in newborns. Pregnancy has little effect on hyperthyroidism. On the contrary, pregnancy often leads to different degrees of remission of hyperthyroidism. However, when pregnancy is combined with severe hyperthyroidism, pregnancy can increase the burden on the heart and aggravate the pre-existing heart disease of hyperthyroid patients. In individual patients, hyperthyroidism can be triggered by childbirth, postpartum bleeding and infection.
Diagnosis
Normal pregnancy resembles the clinical manifestations of hyperthyroidism in many ways due to changes in maternal thyroid morphology and function, such as tachycardia, increased cardiac output, enlarged thyroid gland, warm skin, excessive sweating, fever, and hyperphagia, which are common in both pregnancy and hyperthyroidism, thus making the diagnosis of hyperthyroidism in combination with pregnancy difficult. When signs and symptoms of hyperthyroidism are found during prenatal examination, further functional measurements of the thyroid gland should be done to clarify the diagnosis. The diagnostic criteria for hyperthyroidism in pregnancy are: hypermetabolic syndrome, serum total thyroxine (TT4) ≥ 180.6 nmol/L (14 μg/dl), total triiodothyronine (TT3) ≥ 3.54 nmol/L (230 ng/dl), free thyroxine index (FT4I) ≥ 12.8. The highest level of TT4 < 1.4 times the normal value is considered mild hyperthyroidism. The highest level of TT4 <1.4 times the normal value is mild hyperthyroidism; >1.4 times the normal value is moderate hyperthyroidism; critical illness, hyperthyroid heart disease, heart failure, myopathy, etc. are severe hyperthyroidism.
Treatment measures
(1) Before pregnancy: Because hyperthyroidism has a series of adverse effects on the fetus, if hyperthyroidism is diagnosed, it is appropriate to wait for 1 to 3 years after the condition is stabilized and pregnancy should be avoided during the period of medication (anti-thyroid drugs or radioactive iodine) and contraceptive measures should be taken.
(2) Treatment during pregnancy
(1) Pregnant women with hyperthyroidism should be examined and followed up in high-risk clinics, pay attention to the intrauterine growth rate of the fetus, and actively control hyperemesis.
(2) Mild hyperthyroidism can be tolerated during pregnancy, so for mild cases, anti-thyroid medication is generally not needed because anti-thyroid medication can affect fetal thyroid function through the placenta. However, in severe cases, treatment with antithyroid drugs should be continued. The dose of antithyroid medication should not be too high in the middle and late stages of pregnancy, generally to maintain the mother’s blood TT4 level not more than 1.4 times the upper limit of normal, that is, mild hyperthyroidism. ＞Anti-thyroid drugs should be used only when the level is more than 1.4 times the upper limit of normal. Among the antithyroid drugs, propylthioxypyrimethamine not only blocks the synthesis of thyroid hormone, but also blocks the conversion of T4 into effective T3 in the surrounding tissues, causing the serum T3 level to drop rapidly. The common dose of propylthioxypyrimethamine 150-300mg/d or tabazol 15-30mg/d can be gradually reduced after hyperthyroidism is controlled. Do not use the drug 2 to 3 weeks before the expected delivery date or use the minimum effective amount to control hyperthyroidism. Keep the dosage of propylthiouracil under 200 mg per day and tabazol under 20 mg per day and the likelihood of goiter in the fetus is extremely low. There is a debate on whether to add thyroid hormone to antithyroid drug therapy, because thyroid hormone does not easily pass through the placenta and increases the dose of antithyroid drugs after use. However, combined application can eliminate hypothyroidism caused by antithyroid drugs and prevent hypothyroidism or goiter in the fetus due to the effect of antithyroid drugs.
(3) Since antithyroid drugs can rapidly affect fetal thyroid function through the placenta, some people advocate subtotal thyroidectomy after antithyroid drug treatment and have achieved good results. The procedure is also likely to cause abortion and preterm delivery.
(4) The application of beta-blocker propranolol (Takayasu) at a dose of 10-20mg 3 times a day. Propranolol is an effective treatment for pregnant women with hyperthyroidism, and can relieve the systemic symptoms caused by excessive thyroid hormones. Propranolol is fast-acting and effective, and is suitable for rapid preparation for hyperthyroid crisis and for performing emergency thyroid surgery. However, beta-blockers can cause acute heart failure in patients with early heart failure or metabolic acidosis, and can cause severe hypotension under general anesthesia. Long-term application of propranolol can increase the muscle tone of the uterus, leading to placental dysplasia and intrauterine growth retardation, so it should not be used as the drug of choice in hyperthyroidism during pregnancy.
(5) Obstetrical management: If hyperthyroidism in pregnancy is treated properly, the pregnancy can reach full term, and the baby can be delivered vaginally and live. Hyperthyroidism is not an indication for cesarean delivery. Pregnancy combined with severe hyperthyroidism is associated with higher mortality rate of preterm delivery and perinatal babies, and intrauterine growth retardation is possible.
(6) Puerperium management: postpartum hyperthyroidism has a tendency to recur, so it is advisable to increase the dose of anti-thyroid drugs after delivery. Regarding postpartum breastfeeding, although antithyroid drugs can affect the thyroid function of the infant through breast milk, we believe that the severity of the maternal condition and the dose of antithyroid drugs should be taken into account when considering whether to breastfeed.
(7) Management of hyperthyroidism crisis: stopping antithyroid medication during pregnancy when hyperthyroidism is not controlled, obstetric surgery, postpartum infection and postpartum bleeding can trigger hyperthyroidism crisis, which can lead to high fever, frequent pulse, heart failure, disorientation and coma if not treated in time. Treatment should include large amounts of antithyroid drugs, such as propyl or methylthioxypyrimethamine, 100-200 mg orally every 6 hours, and tabazol or methylphenidate 10-20 mg orally every 6 hours. For those who are not able to take orally, they can be injected via nasal feeding tube. Take compound iodine solution orally, about 30 drops daily. Propranolol 20-40mg, orally every 4-6 hours, or 0.5-1mg intravenously, pay attention to heart function when applying. Risperdal 1 to 2mg, intramuscular injection every 6 hours. Hydrocortisone 200-400mg daily, intravenous; and broad-spectrum antibiotics, oxygen, cold compresses and sedative and antipyretic agents to correct water and electrolyte disorders and heart failure.
(8) Neonatal management: For newborns delivered by hyperthyroid pregnant women, attention should be paid to check for hypothyroidism, goiter or hyperthyroidism, and thyroid function tests.
Maternal TSH, T4 and T3 are difficult to cross the placental barrier, but long-acting thyroid-stimulating hormone (LATS) can easily cross the placental barrier. Therefore, neonatal hyperthyroidism may occur in infants of mothers with hyperthyroidism, and these newborns may show obvious protruding eyes and signs of hyperthyroidism. Neonatal hyperthyroidism may appear immediately after birth or 1 week later. Treatment of neonatal hyperthyroidism includes tabazol 0.5-1 mg/kg daily or propylthioxypyrimethamine 5-10 mg/kg daily in divided doses with compound iodine solution, 1 drop each time, 3 times a day; digitalis in the presence of heart failure and sedation in the presence of agitation.
If the mother has taken antithyroid drugs during pregnancy, there is a risk of temporary hypothyroidism in the newborn, which should be noted.