title: Dose-dependant hypothyroidism in mice induced by commercial trimethoprim-sulfamethoxazole rodent feed.
abstract: Trimethoprim-sulfamethoxazole (TMP-SMX) medication in the feed or water is commonly administered to immunocompro mised mice to prevent the occurrence of Pneumocystis murina (formerly P. carinii) pneumonia. Therapeutic doses of SMX can cause decreased total and free thyroxine (T4) levels in dogs and thyroid hypertrophy and hyperplasia in mice, rats, and dogs. Our primary objective was to determine whether SMX at doses present in commercially available rodent TMP-SMX feed would pro duce hypothyroidism in mice. Plasma T4 levels were determined prior to and after placement of Brand A TMP-SMX feed (daily SMX dose, 240 mg/kg), Brand B TMP-SMX feed (daily SMX dose, 2400 mg/kg), and their respective controls (doses calculated for a 25-g mouse according to vendor's information). T4 levels in the mice fed Brand B TMP-SMX feed were significantly decreased by 2 wk after feed placement. Levels of thyroid stimulating hormone in male and female mice given Brand B TMP-SMX feed were significantly elevated compared with those of control groups at 6 wk after feed placement, when only these mice showed evidence of thyroid hypertrophy and hyperplasia. No significant change in T4 levels occurred over the course of 11 wk in mice given the Brand A TMP-SMX chow or either control feed. In light of the significant clinical hypothyroidism that occurred in our mice while receiving Brand B TMP-SMX diet, we recommend SMX levels more similar to that of Brand A to avoid such unwanted effects which could confound research data.
authors.affiliation: Tri-Institutional Training Program in Laboratory Animal Medicine and Science: The Rockefeller University, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York, USA. lotus_altholtz@merck.com
authors.forename: Lotus Y
authors.initials: LY
authors.lastname: Altholtz
authors.forename: Krista Marie DuBray
authors.initials: KM
authors.lastname: La Perle
authors.forename: Fred William
authors.initials: FW
authors.lastname: Quimby
mesh_terms: D000821:Animal Feed / Q000633:toxicity*; D000818:Animals; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005298:Fertility / Q000187:drug effects; D007037:Hypothyroidism / Q000139:chemically induced / Q000662:veterinary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012376:Rodent Diseases / Q000139:chemically induced*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013972:Thyrotropin; D013974:Thyroxine