Longitudinal study of the effects of chronic hypothyroidism on skeletal muscle in dogs

Objective-To study the effects of experimentally induced hypothyroidism on skeletal muscle and characterize any observed myopathic abnormalities in dogs. Animals-9 female, adult mixed-breed dogs; 6 with hypothyroidism induced with irradiation with 131 iodine and 3 untreated control dogs. Procedures-Clinical examinations were performed monthly. Electromyographic examinations; measurement of plasma creatine kinase, alanine aminotransferase, aspartate aminotransferase, lactate, and lactate dehydrogenase isoenzyme activities; and skeletal muscle morphologic-morphometric examinations were performed prior to and every 6 months for 18 months after induction of hypothyroidism. Baseline, 6-month, and 18-month assessments of plasma, urine, and skeletal muscle carnitine concentrations were also performed. Results-Hypothyroid dogs developed electromyographic and morphologic evidence of myopathy by 6 months after treatment, which persisted throughout the study, although these changes were subclinical at all times. Hypothyroid myopathy was associated with significant increases in plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase 5 isoenzyme activities and was characterized by nemaline rod inclusions, substantial and progressive predominance of type I myofibers, decrease in mean type 11 fiber area, subsarcolemmal accumulations of abnormal mitochondria, and myofilber degeneration. Chronic hypothyroidism was associated with substantial depletion in skeletal muscle free carnitine. Conclusions and Clinical Relevance-Chronic, experimentally induced hypothyroidism resulted in substantial but subclinical phenotypic myopathic changes indicative of altered muscle energy metabolism and depletion of skeletal muscle carnitine. These abnormalities may contribute to nonspecific clinical signs, such as lethargy and exercise intolerance, often reported in hypothyroid dogs. (Am J Vet Res 2009;70:879-889)