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Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

¹Medical Department M (Endocrinology and Diabetes), ²Medical Department C and ³Department of Radiology R, Aarhus University Hospital, Aarhus; ⁵Medical Research Laboratories, University of Aarhus, Aarhus, Denmark; and ⁴Endocrine Research Unit, Mayo Clinic, Rochester Minnesota

Submitted 14 June 2004 ; accepted in final form 7 January 2005

Thyroid hormones have significant metabolic effects, and muscle wasting and weakness are prominent clinical features of chronic hyperthyroidism. To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [¹⁵N]phenylalanine and [²H_4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was icreased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (µg·100 ml^–1·min^–1): –7.0 ± 1.2 Ht vs. –3.8 ± 0.8 Eut (P = 0.04), –4.2 ± 0.3 Ctr (P = 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (µg·100 ml^–1·min^–1): 15.5 ± 2.0 Ht vs. 9.6 ± 1.4 Eut (P = 0.03), 9.9 ± 0.6 Ctr (P = 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10–20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy.

hyperthyroidism; skeletal muscle; amino acids; stable isotopes; tracers; protein synthesis; protein breakdown; energy metabolism

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