ATA has “developed evidence-based recommendations to inform clinical decision making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders”
Part 1 of recommendations are listed with slightly modified wording for easier and succinct reading:
- Median urinary iodine concentrations can be used to assess the iodine status of populations, but single spot or 24-hour urine iodine concentrations are not a valid marker for the iodine nutritional status of individual patients
- All pregnant women should ingest approximately 250 μg iodine daily. To achieve a total of 250 μg iodine ingestion daily, strategies may need to be varied based on country of origin.
- In most regions, including the United States, women who are planning pregnancy or currently pregnant, should supplement their diet with a daily oral supplement that contains 150 μg of iodine in the form of potassium iodide. This is optimally started 3 months in advance of planned pregnancy.
- There is no need to initiate iodine supplementation in pregnant women who are being treated for hyperthyroidism or who are taking LT4.
- Euthyroid, but TPO or TgAb positive pregnant women should have measurement of serum TSH concentration performed at time of pregnancy confirmation, and every 4 weeks through mid-pregnancy.
- Selenium supplementation is not recommended for the treatment of TPOAb positive women during pregnancy
Excerpts from the publication:
Pregnancy has a profound impact on the thyroid gland and its function. During pregnancy, the thyroid gland increases in size by 10% in iodine replete countries, but by 20%-40% in areas of iodine deficiency. Production of the thyroid hormones, T4 and T3, increases by nearly 50%, in conjunction with a separate 50% increase in the daily iodine requirement.
Placental hCG stimulates thyroid hormone secretion, often decreasing maternal TSH concentrations, especially in early pregnancy. But while such transiently suppressed maternal TSH concentrations are often observed and deemed safe, defining the upper reference limit for serum TSH in this population has remained controversial. Furthermore, up to 18% of all pregnant women are thyroid peroxidase (TPOAb) or thyroglobulin antibody (TgAb) positive. Increasingly, data suggest that TPOAb positivity adversely modulates the impact of maternal thyroid status (especially hypothyroidism) on the pregnancy and the developing fetus. Thyroid antibody positivity separately increases the risk of thyroid dysfunction following delivery and during the postpartum period.
While mild hyperthyroidism appears safe for the mother and fetus, moderate to severe hyperthyroidism can prove dangerous.
Normal pregnancy is associated with an increase in renal iodine excretion, an increase in thyroxine binding proteins, an increase in thyroid hormone production, and thyroid stimulatory effects of hCG. All of these factors influence thyroid function tests in the pregnant patient.
Following conception, circulating thyroxine binding globulin (TBG) and total T4 (TT4) concentrations increase by week 7 of gestation, and reach a peak by approximately week 16 of gestation. These concentrations then remain high until delivery. In the first trimester, maternal hCG directly stimulates the TSH receptor, increasing thyroid hormone production and resulting in a subsequent reduction in serum TSH concentration. Therefore, during pregnancy, women have lower serum TSH concentrations than before pregnancy, and a TSH below the nonpregnant lower limit of 0.4 mU/L is observed in as many as 15% of healthy women during the first trimester of pregnancy. The fraction of women with a suppressed TSH falls to about 10% in the second trimester, and 5% in the third trimester.
There is a downward shift of the TSH reference range during pregnancy, with a reduction in both the lower (decreased by about 0.1-0.2 mU/L) and the upper limit of maternal TSH (decreased by about 0.5-1.0 mU/L), relative to the typical non-pregnant TSH reference range. The largest decrease in serum TSH is observed during the first trimester, due to elevated levels of serum hCG directly stimulating the TSH receptor and thereby increasing thyroid hormone production. Thereafter, serum TSH and its reference range gradually rise in the 2nd and 3rd trimesters, but nonetheless remain lower than in non-pregnant women. Since hCG concentrations are higher in multiple pregnancies than in singleton pregnancies, the downward shift in the TSH reference interval is greater in twin pregnancies.
A reduction in the lower TSH reference range is observed during pregnancy in almost all studies. In a small percentage of women, TSH can be undetectable <0.01 mU/L, and yet still represent a normal pregnancy. In addressing the clinical importance of a reduced serum TSH during pregnancy, it is important to note that subclinical hyperthyroidism has not been associated with adverse pregnancy outcomes. Therefore, a maternal TSH concentration that is low but detectable is likely not clinically significant.
Free thyroxine represents only about 0.03% of serum total T4 content. Importantly, only free thyroxine is available for tissue uptake, with the remainder of T4 bound to serum proteins, primarily TBG. Serum total T4 concentrations are measured in the nanomolar range, while FT4 concentrations are measured in the picomolar range.
Because of increased thyroid hormone production, increased renal iodine excretion, and fetal iodine requirements, dietary iodine requirements are higher in pregnancy than they are for nonpregnant adults. Women with adequate iodine intake before and during pregnancy have adequate intrathyroidal iodine stores and have no difficulty adapting to the increased demand for thyroid hormone during gestation.
The U.S. Institute of Medicine recommended dietary allowances to be used as goals for individual total daily iodine intake (dietary and supplement), are 150 μg/d for women planning a pregnancy, 220 μg/d for pregnant women, and 290 μg/d for women who are breastfeeding. The WHO recommends 250 μg/d for pregnant and lactating women.
TPOAbs or TgAbs are present in 2-17% of unselected pregnant women. The prevalence of antibodies varies with ethnicity. In U.S.populations, thyroid antibodies are most frequent in Caucasian and Asian women and least frequent in African-Americans.
TPO antibodies are able to cross the placenta. At the time of delivery, cord blood TPOAb levels strongly correlate with third-trimester maternal TPOAb concentrations. However, maternal passage of either TPOAb or TgAb is not associated with fetal thyroid dysfunction.
Some studies evaluating non-pregnant women have shown that selenium is capable of diminishing TPOAb concentrations. However, this has not been observed in all studies. Negro et al. noted that euthyroid, TPOAb positive pregnant women randomized to treatment with 200 µg/day selenium not only had a significant decrease in the frequency of postpartum thyroid dysfunction, but also had lower TPOAb concentrations during pregnancy compared to those in the untreated group. Importantly, this trial did not measure urinary iodine, a potential confounder since iodine status may influence the thyroidal effects of selenium.
However, in another recent randomized clinical trial performed in mildly iodine deficient British pregnant women, treatment with 60 mcg selenium daily did not affect TPO concentrations nor TPOAb positivity. Thus, conflicting data regarding selenium supplementation make any generalized recommendation unreliable, especially to regions with different iodine and/or selenium intakes. In addition, patients treated with selenium could be at higher risk for developing type 2 diabetes mellitus. For these reasons, the risk-to-benefit comparison does not presently support routine selenium supplementation of TPOAb positive women during pregnancy.