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

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 [N-15] phenylalanine and [H-2(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 (mu g center dot 100 ml(-1) center dot 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 (mu g center dot 100 ml(-1) center dot 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.