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Dibutyl-phthalate exposure from mesalamine medications and serum thyroid hormones in men
Authors:Feiby L. Nassan  Tim I.M. Korevaar  Brent A. Coull  Niels E. Skakkebæk  Stephen A. Krawetz  Molly Estill  Elizabeth J. Hait  Joshua R. Korzenik  Jennifer B. Ford  Ralph A. De Poortere  Maarten A. Broeren  Alan C. Moss  Thomas R. Zoeller  Russ Hauser
Affiliation:1. Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA;2. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA;3. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA;4. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA;5. Department of Growth and Reproduction, EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;6. Department of Obstetrics & Gynecology, Center for Molecular Medicine & Genetics, Wayne State University, Detroit, MI, USA;7. Division of Gastroenterology, Children''s Hospital Boston, Harvard Medical School, Boston, MA, USA;8. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA, USA;9. Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, Veldhoven, De Run, 4600, the Netherlands;10. Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;11. Department of Biology, University of Massachusetts, Amherst, MA, USA;12. Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Abstract:

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.
Keywords:Phthalate  Endocrine disruptor  Thyroid  Hormones  Men
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