AJVR, Vol 73, No. 4, April 2012 529 A mong the numerous functions of thyroid hor- mones is their integral role in glucose homeostasis. Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs Natalie Hofer-Inteeworn, Dr med vet, MS; David L. Panciera, DVM, MS; William E. Monroe, DVM, MS; Korinn E. Saker, DVM, PhD; Rebecca Hegstad Davies, PhD; Kent R. Refsal, DVM, PhD; Joseph W. Kemnitz, PhD Objective—To determine the effects of hypothyroidism on insulin sensitivity, glucose toler- ance, and concentrations of hormones counter-regulatory to insulin in dogs. Animals—8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs. Procedures—The insulin-modified frequently sampled IV glucose tolerance test and min- imal model analysis were used to determine basal plasma insulin and glucose concen- trations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index. Growth hormone response was assessed by stimulation and suppres- sion tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured and dual energy x-ray absorptiometry was performed to evaluate body composition. Results—Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposi- tion index were not different between groups. Basal serum GH and IGF-1 concentrations as well as abdominal fat content were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged. Conclusions and Clinical Relevance—Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with dis- eases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications. (Am J Vet Res 2012;73:529–538) Hypothyroidism has been associated with poor glyce- mic control in diabetic dogs but has been suggested to be an uncommon cause of insulin resistance. 1 However, diabetes mellitus was the most common concurrent disease in a retrospective study 2 of dogs with hypo- thyroidism, and hypothyroidism was one of the most commonly diagnosed concurrent disorders in dogs with diabetes mellitus. 3 Findings in dogs with experi- Received December 6, 2010. Accepted March 4, 2011. From the Departments of Small Animal Clinical Sciences (Hofer-Inteeworn, Panciera, Monroe) and Large Animal Clinical Sciences (Saker), Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061; the Veterinary Di- agnostic Laboratory, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108 (Davies); the Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, Lansing, MI 48824 (Refsal); and the In- stitute for Clinical and Translational Research and Department of Physiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53715 (Kemnitz). Dr. Hofer-Inteeworn`s present address is Clinic for Small Animal Internal Medicine, Vetsuisse-Faculty University of Zürich, 8057 Zürich, Switzerland. Dr. Saker’s present address is Department of Molecular and Biomed- ical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Supported in part by a grant from the Veterinary Memorial Fund, Vir- ginia-Maryland Regional College of Veterinary Medicine, Virginia Tech. Presented in abstract form at the American College of Veterinary In- ternal Medicine Conference, San Antonio, Tex, June 2008. The authors thank Stephanie Milburn, Barbara Kafka, and Dana Calicott for technical assistance and Dr. Stephen Were for statistical consultation. Address correspondence to Dr. Panciera (panciera@vt.edu). ABBREVIATIONS AIR G Acute insulin response to glucose AUC Area under the curve CV Coefficient of variation DEXA Dual energy x-ray absorptiometry DI Disposition index FSIGT Frequently sampled IV glucose tolerance test GH Growth hormone GHRH Growth hormone–releasing hormone GLUT Glucose transporter HGO Hepatic glucose output IGF Insulin-like growth factor SG Glucose effectiveness S I Insulin sensitivity T 4 Thyroxine TSH Thyroid-stimulating hormone Unauthenticated | Downloaded 09/01/22 07:13 PM UTC