Periconceptional changes in thyroid function: a longitudinal study

Abstract

BackgroundLimitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.MethodsWomen (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.ResultsPre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.ConclusionsTSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.

Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

“…However, the complexity and dynamics of the hormonal changes occurring during pregnancy, especially in the first trimester, make the establishment of reference values more difficult. Changes in iodine metabolism, the production of chorionic gonadotropin (beta-hCG), increases in thyroid hormone carrier proteins, changes in excretion and elevation of thyroid hormones levels per se, alter the reference values (26). Thus, it is important that laboratories establish referen-surgery (30); untreated primary adrenal insufficiency (31); cross-reaction of TSH with heterophilic antibodies against rat proteins (32); and mutations in the TSH receptor (33).…”

The Impact and Management of Subclinical Hypothyroidism for Improving Reproductive Outcomes such as Fertility and Miscarriage

“…In a study of 60 women, Balthazar and Steiner looked at periconceptional changes in TSH levels. 39 They found that in women with antithyroid antibodies, TSH levels were more variable from the preconceptional to early pregnancy stage compared with women without antithyroid antibodies. 39 Other theories have included associated alterations in cytokines and T-helper cells.…”

“…39 They found that in women with antithyroid antibodies, TSH levels were more variable from the preconceptional to early pregnancy stage compared with women without antithyroid antibodies. 39 Other theories have included associated alterations in cytokines and T-helper cells. In a small study of 53 pregnant women, Turhan Iyidir et al found that women with thyroid autoimmunity had higher levels of IL-2 and IL-17 compared with controls.…”

Thyroid Autoimmunity and Reproductive Function

“…Pre-pregnancy TSH values were significantly higher than those in early pregnancy, although no such changes in free T4 values were noted. 35 Thus, it appears that thyroid hormone levels differ in preconception versus early pregnancy, which should be taken into consideration when crafting screening guidelines.…”