Contributor: Dr. John V. Dacus
Last Update: 01/01/15
Thyroid disease is the second most common endocrinopathy in pregnancy after diabetes. Hypothyroidism occurs in about 2.5% of pregnancies and hyperthyroidism in 0.2% of pregnancies.
Untreated hypothryroidism has been associated with preeclampsia, placental abruption, and intrauterine growth restricted infants. Subclinical hypothyroidism has been reported to increase the risk of neurodevelopmental problems in children. Untreated hyperthyroidism increases the risk of preeclampsia, intrauterine growth restriction, neonatal thyroid dysfunction, and maternal thyroid storm.
Thyrotropin releasing hormone (TRH), produced by the hypothalamus, stimulates release of thyroid stimulating hormone (TSH) from the pituitary gland which then causes the thyroid gland to secrete thyroxine (T4) and triiodothyronine (T3).
Thyroid binding globulin (TBG) increases in pregnancy secondary to a rise in estrogen. This results in an increase in total T4 and total T3 but the free T4 and free T3 do not increase. Plasma TSH does not cross the placenta and T4 & T3 cross minimally.
Symptoms of hyperthyroidism include tachycardia (even at rest), tremors, and heat intolerance, weight loss, diarrhea, sweating, hypertension, and goiter. Many of these symptoms mimic normal adaptations to pregnancy. The most common cause of hyperthyroidism in pregnancy is Graves disease (95%). Other causes may be gestational trophoblastic disease, nodular goiter, and viral thyroiditis.
The diagnosis of hyperthyroidism in pregnancy is made by obtaining a depressed serum TSH (less than 0.1 mU/L) and an elevated total T4 (TT4) greater than 1 1/2 times the upper limit of normal nonpregnant values. Occasionally the TT4 is normal and an elevated total T3 (TT3) greater than 1 1/2 times the upper limit of normal nonpregnant value is diagnostic of T3 thyrotoxicosis.
The American Thyroid Association and the Association of Clinical Endocrinologists recommend use of serum TSH together with total T4 as the thyroid test of choice during pregnancy (4). Some studies have shown free T4 immunoassays to be flawed in pregnancy (3).
The treatment of hyperthyroidism in pregnancy is initially medical using a thionamide. These drugs block the synthesis and not the release of thyroid hormones.
A CBC should be obtained as baseline because agranulocytosis (incidence of 0.1%) is a dangerous, rare complication. If the patient complains of fever or sore throat an immediate WBC count should be obtained.
The FTI should be checked every 3-4 weeks and as the value is falling, the dose of thionamide should be cut in half. The lowest dose to keep the FTI in the upper range of normal should be sought.
Methimazole (Tapezol) is the thionamide of choice according to the latest information from the FDA. It should be started at an initial dose of 10 to 15 milligrams once daily. According to the FDA, PTU (propylthiouracil) should only be used if the patient is allergic to Tapezol or during the first trimester of pregnancy because of the possible teratogenesis of Tapezol (questionable increase in cutis aplasia in fetus).
Since Graves disease is autoimmune in nature, there are exacerbations and remissions. The dose of Tapezol at times may be minimal and at times, especially after 12 weeks of therapy the drug may be discontinued and the FTI remain in the normal range.
Postpartum the patient may undergo an exacerbation even if she has previously been treated with I131 or thyroidectomy. There may be thyroid stimulating antibodies (TSA) still present. Thyroid function tests should be obtained 7-10 days postpartum in all patients with a history of previous or current hyperthyroidism.
Obstetric management should include serial ultrasonic exams for growth (at least each trimester) and evaluation for possible fetal goiter. Fetal antenatal testing is recommended for uncontrolled hyperthryoidism beginning at 34 weeks.
Severe hyperemesis gravidarum may be associated with elevated liver function tests and abnormal thyroid function (low TSH, elevated FTI) in 66% of cases. These tests return to normal with reduction of the nausea and vomiting. Thionamides are not indicated.
Patients with hyperemesis gravidarum will not demonstrate many of the symptoms of hypothyroidism. With hydration tachycardia disappears, usually patients will report no diarrhea or heat intolerance or increased perspiration. There are no abnormal thyroid test results that are able to distinguish hyperemesis gravidarum from hyperthyroidism.
Symptoms of hypothyroidism include weight gain, lethargy, intolerance to cold, hair loss, brittle nails, dry skin, and goiter. Worldwide iodine deficiency is the most common cause; but in the U.S. it is Hashimoto’s disease. This is an autoimmune disease often with anti-peroxidase antibodies. Other causes include thyroidectomy and thyroid ablation with I131.
The diagnosis of hypothyroidism is made by an TSH greater than 2.5 mU/L in the first trimester or a TSH greater than 3.0 mU/L in the second or third trimesters. No further testing is needed. The free T4 index by our lab’s methodology does not allow precise results of less than 16%. The free T4 has been shown to be less accurate in pregnancy, and there are no available data regarding low values in pregnancy for the TT4.
Thyroxine replacement is indicated to normalize the TSH. Starting doses of 100 to 150 micrograms daily of Synthroid are recommended. Most women may need increasing amounts of replacement therapy, so TSH should be checked every 6-8 weeks and dosage of thyroxine altered accordingly. Ferrous sulfate interferes with the intestinal absorption of thyroxine so the two medications should be taken at least 4 hours apart.
Serial ultrasound exams are indicated with attention to possible fetal goiter if hypothyroidism is secondary to treated Grave’s Disease. Patients with hypothyroidism are at increased risk for gestational diabetes and preeclampsia so enhanced awareness for these two complications is desirable.
The newborn of the patient with thyroid disease may be at risk for hyperthyroidism or hypo-thyroidism. Pediatricians should be made aware of the mother’s condition and any medications she may be taking.
Definition – High TSH and normal FTI and FT3I
Requires no therapy during pregnancy as judged by recent literature.
Definition – Low TSH and normal FTI and FT3I.
Require no therapy during pregnancy as judged by recent literature.
Thyroid storm is a medical emergency that occurs in 1-2% of hyperthyroidism in pregnancy. The symptoms are adrenergic in nature: fever, tachycardia, sweating, nervousness, confusion, seizures, vomiting, diarrhea, cardiac arrhythmias, and hypertension. Precipitating causes may be infection, surgery, labor or delivery. Historical data have shown up to a 20% mortality associated with thyroid storm.
Management of Thyroid Storm
- Methimazole (Tapezol) 20 milligrams PO or rectally every 6 hours
- Potassium iodide 2-5 drops orally 1-2 hours after Tapezol & repeated every 8 hours or sodium iodine 1 gram IV every 8 hours beginning 1-2 hours after Tapezol
- Dexamethasone 2 mg IV every 6 hours for 4 doses to decrease peripheral conversion of T4 to T3
- Propanolol 20-80 mg orally every 6 hours or 1-2 mg IV every 5 min to inhibit adrenergic effects of increased thyroid hormone.
- Phenobarbital 30 mg orally every 4 hours to reduce agitation
- Nasal O2
- IV fluids & electrolytes
- Cooling blanket
- Maternal & Fetal Monitoring preferably in intensive care.
- Rashid, M., Rashid MH. Obstetric management of thyroid disease. OBGYN Survey 2007;62:680-688
- 2007 Compendium: Thyroid disease in pregnancy. Vol 2:664-671
- Lee RH, Spencer CA, Mestman JH, et al. Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 2009;200:260.e1-260.e6.