Thyroid Changes during Pregnancy
Thyroid function is important in fetal development and thyroid disease is not uncommon during pregnancy. For these reasons, it is important to understand the changes in thyroid function that occur during pregnancy.
Increased concentration of estrogen during pregnancy changes the glycosylation of thyroxine binding globulin (TBG), which increases the circulating half-life. The liver increases TBG synthesis and reduces TBG clearance. Together, these changes result in a two to threefold increase in plasma TBG levels. TBG peaks at about 20 weeks and remains elevated throughout the remainder of pregnancy. The affinity of thyroxine (T4) for TBG does not change.
The increased TBG concentration results in a parallel increase in total T4 and T3. Nonpregnant reference intervals for total T4 and T3 cannot be used during pregnancy. The general practice is to multiply the upper reference limit by 1.5 to get pregnancy specific reference intervals for pregnancy.
hCG has homology with TSH and can bind to the TSH receptor. HCG concentration peaks between 8 and 12 weeks of gestation. At this time, TSH may be slightly decreased but tends to remain within the reference interval. If hCG levels rise above 400,000 IU/L, 100% of pregnant women have TSH levels below 0.2 mIU/mL.
The 2017 guidelines from the American Thyroid Association (ATA) raised the upper limit of normal for TSH from 2.5 mIU/L to 4.0 mIU/L. Adverse obstetric effects occur in pregnant women who have TSH levels above 2.5 mIU/L and thyroperoxidase (TPO) antibodies, but not in women who do not have TPO antibody. Adverse effects are not consistently seen in the latter population until TSH levels increase above 4.0 mIU/L. For this reason, the latest ATA guidelines state that pregnant women with TSH concentrations greater than 2.5 mIU/L should be tested for anti-thyroid peroxidase (TPO) antibodies.
Thyroglobulin is produced by follicular cells and is the precursor of thyroid hormones. Due to an increased demand for T4 during the first trimester, thyroid volume increases by approximately 10% and the plasma concentration of thyroglobulin increases.
Free T4 may increase slightly during the first trimester, due to the action of hCG on the TSH receptor. However, the concentration of free T4 is decreased during the second and third trimesters. This decrease is due to the increase in TBG concentration, increase in renal iodide clearance, and an increased physiologic demand for thyroxine.
Reference
Ann Gronowski, CAP Today, October 2018
