A Longitudinal Study of the Effects of Chronic Experimental Hypothyroidism on Canine Skeletal Muscle
The purpose of this study was to evaluate the effects of chronic hypothyroidism on canine skeletal muscle and carnitine metabolism. It was hypothesized that carnitine metabolic derangements occur in hypothyroid dogs and may participate in the pathogenesis of hypothyroid myopathy, as thyroid hormone dependent alterations in gene expression of carnitine palmitoyltransferase have been demonstrated in other species.
Nine clinically normal, euthyroid, mixed breed females were studied. Hypothyroidism was induced by 131Iodine irradiation in six dogs; three served as untreated controls. Clinical, electrophysiologic, muscle histopathologic, histomorphometric and ultrastructural examinations, plasma biochemical analyses, and plasma, urine, and muscle carnitine fractional quantifications were performed at baseline and 6, 12, and 18 months after induction of hypothyroidism. Data were analyzed using repeated measures ANOVA.
At baseline, no differences between groups were detected for any variable. All animals remained asymptomatic for neuromuscular disease throughout the study. Hypothyroid dogs developed electromyographic, and significant biochemical, histopathologic, and histomorphometric evidence of myopathy by 6 months, which persisted throughout the study. Hypothyroid dogs developed increases in plasma CK, AST, and LDH activities, increased urinary excretion of carnitine, and depletion of skeletal muscle carnitine. Histomorphologically, the myopathy was characterized by nemaline rod inclusions, temporally progressive Type I myofiber predominance and Type II myofiber atrophy, and subsarcolemmal accumulations of abnormal mitochondria.
This canine model resulted in reproducible subclinical myopathic alterations similar to those described in dogs with spontaneous hypothyroidism. Further studies are needed to determine if observed carnitine metabolic alterations contribute to the pathogenesis of hypothyroid myopathy, or occur as epiphenomena.