The effect of thyroid replacement in dogs with suboptimal thyroid function on owner-directed aggression: A randomized, double-blind, placebo-controlled clinical trial

The efficacy of thyroid hormone replacement therapy (THRT) as treatment for ownerdirected aggression in client-owned dogs with borderline low thyroid hormone levels was evaluated by means of a 6-week-long, parallel design, double-blind placebocontrolled study. The designation of “borderline hypothyroid” was made if the dog’s free normal thyroxine (T4) value was frankly low or in the bottom 20th percentile of the normal range and either total T4, total triiodothyronine (T3), or free T3 was frankly low or in the bottom 30th percentile of the normal range. The presence of thyroid autoantibodies also qualified a dog for enrollment. Owners recorded the number of aggressive episodes directed toward family members on a daily basis for 8 weeks (2-week baseline phase and 6-week study phase). Twenty-nine dogs completed the study; 14 in a treatment group and 15 in a placebo group. The median number of aggressive episodes per day decreased significantly from baseline in both treated and placebo group dogs in weeks 1-2, 3-4, 5-6, and week 6 (treatment, c2 1⁄4 24.8, P < 0.001; placebo, c2 1⁄4 20.2, P < 0.001), however the median frequency of aggression was significantly lower in the treatment group (1.21 episodes/day) than in the placebo group (1.71 episodes/day) during week 6 of the study (c2 1⁄4 4.047, P 1⁄4 0.044). Three thyroxine-treated dogs had borderline-low thyroid levels on the final day of the study (day 42). When aggression frequency was compared between the treatment and placebo groups after the removal of 3 thyroxine-treated dogs, the treatment group did not have a significantly lower aggression frequency than the placebo group during week 6 (Kruskal–Wallis statistic: c2 1⁄4 3.035, n 1⁄4 26, P 1⁄4 0.08). The authors discuss the role of thyroid hormones in the regulation of aggression and other cognitive issues and provide rationale for using THRT in dogs exhibiting owner-directed aggression that also have low normal or baseline thyroid hormone levels. 2013 Elsevier Inc. All rights reserved.