Dibutyl-phthalate exposure from mesalamine medications and serum thyroid hormones in men.

BACKGROUND: Dibutyl phthalate (DBP) is an endocrine disruptor and used in some medication coatings, such as mesalamine for treatment inflammatory bowel disease (IBD). OBJECTIVES: To determine whether high-DBP from some mesalamine medications alters thyroid function. METHODS: Seventy men with IBD, without thyroid disease or any radiation history participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background exposure) at baseline crossed-over to DBP-mesalamine (high exposure) then crossed-back to non-DBP mesalamine (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). Serum concentrations of total triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). RESULTS: After crossover in B1HB2-arm (26 men, 134 samples), T3 decreased 10% (95% confidence interval (CI): 14%,-5%), T3/T4 ratio decreased 8% (CI: 12%,-3%), TPOAb, and TgAb concentrations decreased, 11% (-20%, -2%) and 15% (-23%, -5%), respectively; after crossback, they increased. When men in the H1BH2-arm (44 men, 193 samples) crossed-over, T3 decreased 7% (CI: -11%, -2%) and T3/T4 ratio decreased 6% (CI: -9%, -2%). After crossback, only TgAb increased and FT4 decreased. CONCLUSIONS: High-DBP novel exposure or removal from chronic high-DBP exposure could alter elements of the thyroid system, and most probably alters the peripheral T4 conversion to T3 and thyroid autoimmunity, consistent with thyroid disruption. After exposure removal, these trends were mostly reversed.

Reference Ranges and Determinants of Thyroid Function During Early Pregnancy: The SELMA Study.

Context: Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for triiodothyronine measurements, and most studies do not take into account thyroid antibodies or human chorionic gonadotropin. Objective: To determine reference ranges and to identify/quantify determinants of TSH, free T4 (FT4), free triiodothyronine (FT3), total T4 (TT4), and total triiodothyronine (TT3). Design, Setting, and Participants: This study included 2314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5th to 97.5th percentiles after excluding thyroperoxidase antibody (TPOAb)-positive and/or thyroglobulin antibody (TgAb)-positive women. Intervention: None. Main Outcome Measures: TSH, FT4, FT3, TT4, and TT3 in prenatal serum. Results: After exclusion of TPOAb-positive women, reference ranges were as follows: TSH, 0.11 to 3.48 mU/L; FT4, 11.6 to 19.4 pmol/L; FT3, 3.72 to 5.92 pg/mL; TT4, 82.4 to 166.2 pmol/L; and TT3, 1.28 to 2.92 nmol/L. Additional exclusion of TgAb-positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. Body mass index (BMI) and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4, and TT3. Conclusions: We show that the exclusion of TgAb-positive women on top of excluding TPOAb-positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4, and TT3 that could reflect endocrine-disrupting effects and/or effects on thyroid hormone transport or deiodination.