Are TSH normal reference ranges adequate for pregnant women?

Abstract

A ccording to some investigators, pregnancy represents a "stress test" for the thyroid gland (1) since an intact gland and an appropriate iodine supply are needed for an adequate hormone supply for mother and fetus. Patients with mild underlying thyroid disease or inadequate dietary iodine may fail the test and become hypothyroid. Typically, thyroid hormone production and daily iodine intake increase by approximately 50% in the first few weeks of pregnancy (2). This greater demand on the thyroid gland is due to a series of physiological changes occurring during pregnancy. One of the important alterations is the elevated level of human chorionic gonadotropin (hCG) which, by being structurally similar to TSH, has a direct stimulating action on the thyroid gland through the TSH receptor. During pregnancy, the hCG peak occurs at the end of the 1 st trimester, followed by a reduction to a plateau during the second and third trimesters. The thyrotropic effect of hCG results in an increased production of thyroid hormones (TH) which is reflected on a transitory increase in free T4 (FT4) at the end of the 1 st trimester (3,4). Concomitantly, the increase in hCG results in a reduction of TSH; with the progression of pregnancy and the decline of hCG there is an elevation of TSH (5). Compared to pre-pregnancy concentrations, thyroxine binding globulin (TBG) increases 2-3 times by about the 20 th week of gestation. This is due to the estrogen-stimulated increase in the hepatic production of TBG and to a reduced clearance of the sialylated, heavier, forms of the molecule. This elevation causes, on average, a 1.5-fold increase of total tri-iodothyronine l (TT3) and thyroxine (TT4) around the 16 th week of gestation. Extra TH production is also necessary to cover the losses due to placental deiodination.During pregnancy, the maternal requirements of iodine increase due to several reasons (4,6). One of the mechanisms postulated is related to the greater renal loss of iodine, although its significance has been debated (7). At the same time, iodine is transported to the growing fetus through the placenta, being necessary in order to cover the increased maternal production of TH due to the increase in TBG.The diagnosis of hypothyroidism during pregnancy is fully dependent on thyroid function tests. Four guidelines have been recently published by experts' groups in North America, Europe and Brazil regarding the diagnosis and management of thyroid disease in pregnancy (1,6,8,9). For the interpretation of thyroid function tests, all guidelines similarly recommend 2.5 mUI/L as the upper normal limit for TSH in the 1 st trimester if the normal range has not been established for that region. All guidelines also warn about the use of FT4 in pregnancy. The ATA recommends the determination of TT4 and the calculation of the free T4 index (FTI) as preferable to FT4 by immunoassay, although some investigators have argued that this is a retrograde and misguided measure (10).

Trimester-specific thyroid-stimulating hormone: An Indian perspective

“…Serum human chorionic gonadotropin concentrations tend to be higher, and TSH concentrations tend to be lower in women with multiple pregnancies. [ 6 ]…”

“…In general, the 97.5 th percentile of TSH for the first trimester is located in two groups: according to the Architect, Beckman, and Immulite platform, it is about 3.0 mIU/L, while according to Centaur and Roche, it is close to 4 mIU/L. [ 6 ]…”

Region-specific reference intervals for TSH in pregnancy: time for changes in Brazil

“…Pregnancy-and local specific reference limits for TSH can be markedly affected by multiple prenalytical and analytical factors, such as age, gender, ethnicity, antithyroid antibodies, iodine status, TSH assays, and alterations on proteins and free fatty acids levels (11). In addition, the non-Gaussian distribution and a high inter individual variation of TSH levels in the normal population confers an extra challenge (12).…”