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M. D. Katz |
Thyrotropin and preterm birth
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OR, 1.04 (95% CI, 1.00-1.09); P = .04 |
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Fig. 12.2 The Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth (JAMA 2019; 322(7):632–41)
Maternal Hyperthyroidism: Diagnosis
Hyperthyroidism complicates pregnancy less frequently than hypothyroidism. The TSH is decreased with a free T4 and/or free T3 above trimester speci c ranges. As previously discussed, TFTs can be dif cult to interpret during pregnancy, confounding the diagnosis of hyperthyroidism. A low TSH may prevail due to the elevated hCG stimulating the TSH receptor. Graves’ disease is the most common cause of hyperthyroidism in women of reproductive age. It is due to antibodies which stimulate the TSH receptor (TRAb), namely thyroid stimulating immunoglobulin (TSI) and thyrotropin binding inhibitory immunoglobulin (TBII). Clinically, goiter and orbitopathy with palpitations, tremors, hyperdefecation, heat intolerance, and weight loss may result. More common than Graves’ during pregnancy is transient gestational thyrotoxicosis and hyperemesis gravidarum, both of which typically improve during the second half of pregnancy. Distinguishing between Graves’ disease and transient gestational thyrotoxicosis is mandatory, as the treatment differs. T3 values are often disproportionately higher than T4 levels in Graves’ disease. Antithyroid drugs (ATD) are not indicated for transient gestational thyrotoxicosis, whereas these medications and surgery, are reasonable options for women with Graves’ disease who are either pregnant or contemplating pregnancy. Graves’ disease often abates during the latter half of pregnancy, only to fare postpartum. Measurement of TRAb, which are positive in approximately 95% of Graves’ patients, may be necessary to distinguish between these two diagnoses. Pregnant
12 Thyroid and Reproduction |
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women with a history of Graves’ disease should also be evaluated for TSI every trimester, as these antibodies cross the placenta and cause neonatal hyperthyroidism at a rate of approximately 20%.
Maternal Hyperthyroidism: Treatment
Untreated Graves’ disease during pregnancy is associated with miscarriage, premature labor, low birth weight, stillbirth, preeclampsia, and maternal heart failure. It is always best to de nitively treat hyperthyroidism prior to conception. Due to the fact that antithyroid drugs cross the placenta and the fetus is especially sensitive, the lowest possible dose should be administered to avoid fetal hypothyroidism and goiter, maintaining the mother mildly hyperthyroid. Some women can therefore be closely monitored every 4 weeks without treatment. For symptomatic control, prior to ATD taking effect, low-dose beta-blockers, speci cally propranolol or metoprolol can briefy be used.
Two ATD, known as thionamides, are available in the United States, propylthiouracil (PTU) and methimazole (MMI). Due to the fact that liver toxicity is greater with PTU, MMI is preferred with the exception of the rst trimester of pregnancy. This is because the teratogenic effects of these medications are less severe with PTU. These include aplasia cutis, a scalp defect and more serious abnormalities such as esophageal and choanal atresia, omphalocele, and omphalomesenteric duct anomalies. Agranulocytosis is another potentially life-threatening side effect of thionamides, and therefore the complete blood count (CBC) needs to be monitored in addition to liver function tests (LFTs). Thus, maternal considerations also mandate using the lowest possible dose. Initial thionamide doses are generally the highest and are typically halved within 2–3 weeks to 25–50 mg PTU bid or 2.5 mg methimazole daily, depending on trimester and severity of hyperthyroidism. Low doses of MMI are reportedly safe for nursing women.
In cases of intolerance to thionamides, radioiodine treatment is contraindicated for a minimum of 6 months prior to and during pregnancy. Although usually not recommended, thyroidectomy is a reasonable option for women with Graves’ disease who are planning pregnancy, especially those with diminished ovarian reserve. Thyroidectomy is optimally performed during the second trimester if necessary.
Postpartum Thyroiditis
Postpartum thyroiditis usually entails an initial hyperthyroid phase beginning shortly after delivery with a duration of approximately 2–4 months. It often remains undiagnosed as symptoms suggestive of hyperthyroidism may be common postpartum. It is a painless infammation of the thyroid gland and typically progresses to hypothyroidism, approximately 3–12 months after delivery. Permanent
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