Comparative analytical evaluation of thyroid hormone levels in pregnancy and in women taking oral contraceptives: a study from an iodine deficient area

Abstract

Increase of serum thyroxine binding globulin (TBG) resulting from estrogen action may lead to problems in thyroid diagnostics. The aim of the present study was to define the most diagnostically reliable thyroid parameters in women exposed to differentially elevated estrogens. Sera of three groups of healthy women were analyzed: women taking no medicine (controls), those taking oral contraceptives and pregnant women (in weeks 16 or 32 of gestation). All women involved in the study lived in a moderately iodine-deficient geographical area. Thyroid stimulating hormone (TSH), TBG, total thyroxine (T4), total tri-iodothyronine (T3) and free T3 were determined and free T4 indices (total T4 x T3 uptake; total T4/thyroxine binding capacity (TBC); total T4/TBG) were calculated. Free T4 was measured simultaneously with a one-step T4-analog enzyme-linked immunosorbent assay (ELISA), a labeled T4 antibody radioimmunoassay (RIA), and a two-step microparticle enzyme immunoassay (MEIA). Estrogen-dependent differences were found in all investigated parameters; however, they remained in the reference interval for TSH, total T4 x T3 uptake, total T4/TBC,free T3 and free T4 MEIA. It was concluded that simultaneous estimations of free T4 and free T3 should follow a primary TSH measurement. The necessity of a distinct reference range has emerged for free thyroid hormones in midterm and late pregnancy as well as in the use of oral contraceptives, especially in iodine-deficient areas.

Chronic Treatment with Low Doses of Estradiol Affects Pituitary and Thyroid Function in Young and Middle-aged Ovariectomized Rats

“…Another report describing the effect of daily injections with 2 lg E2B in ovariectomized rats also reported an elevation of TSH levels (Chen and Walfish 1978). In contrast, our results are confirmed by several human studies that did not detect alterations in TSH serum levels in women taking oral contraceptives (Spitz et al 1983;Kuhl et al 1985;Toldy et al 2004).…”

Gestation-Specific Thyroxine and Thyroid Stimulating Hormone Levels in the United States and Worldwide

“…Tables 3 and 4, there is an increase in TSH levels from the first trimester onward in areas of some iodine deficiency, whereas FT4 levels decrease. This is true for some countries in Europe and for Japan 9,11,35,42 and is not as pronounced as the increase from 1.2 to 3.3 mIU/L during the third trimester in India. 41 In women who gave birth to "small for date" babies, babies born with body weight less than 2.5 kg at term, the increase is visibly significant.…”

“…The tables combine either longitudinal or cross-sectional studies and reported means and reference intervals (Table 3) for TSH, T4, T3, FT4, and urinary iodide from the Europe, India, Africa, Middle East, and Japan. 9,11,[34][35][36][37][38][39][40] Medians and interquartile ranges from Singapore, Hong-Kong, China, Sudan, and Sweden are combined in Table 4. [41][42][43][44][45] Comparison of these data suffers from several drawbacks because some of the studies rely on very few subjects, whereas others rely on hundreds and even thousands of participants.…”

“…FT4 slightly decreases in most studies, although FT4 methods of analysis are notorious for their variability in results, even within the same study population. 18,19,35 Mild to moderate iodine deficiency is still present in certain countries or geographic areas despite national efforts to implement the mandatory use of iodized salt to affect T4 and TSH levels. 36,37 Furthermore, iodine intake may vary unexpectedly because of significant variations in the natural iodine content of the local food and water and because of the variability in response to supplementation.…”

New Reference Intervals for Thyrotropin and Thyroid Hormones Based on National Academy of Clinical Biochemistry Criteria and Regular Ultrasonography of the Thyroid

“…With the exception of the TSH results, all other thyroid hormones were strongly dependent on gender or the use of oral contraceptives in the multiple regression analysis. This dependency is attributable to the well-known impact of sex hormones and oral estrogens on thyroid function (11,25,26 ). The estrogen-dependent increases in total T 3 or T 4 may be adjusted for the concentration of thyroxine-binding globulin (TBG) by its direct determination or by the measurement of T-uptake values.…”