Skeletal muscle and whole body protein turnover in thyroid disease

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Abstract
The effects of disturbances of thyroid hormone secretion on leg and whole body amino acid and protein metabolism have been investigated in seven patients with untreated thyrotoxicosis and eight patients with untreated hypothyroidism; the results were compared to those obtained in 11 normal control subjects. After treatment, the patients were restudied. Arterio‐venous exchanges of tyrosine and 3‐methylhistidine across leg tissue in the post‐absorptive state were used as indices of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using stable isotope labelling techniques with 1‐[1‐13C] leucine. Efflux of tyrosine from leg tissues was six‐fold greater in patients with untreated thyrotoxicosis than in normal control subjects (– 19·39 ± 2·21 vs. – 4·20 ± 0·31 nmol 100 g‐1 leg tissue min‐1, P‐1 leg tissue min‐1 vs. 0·14 ± 0·02 nmol 100 g‐1 leg tissue min‐1). After treatment, when the thyrotoxic patients became euthyroid, tyrosine efflux was normalized (at – 4·94 ± 0·84 nmol 100 g‐1 leg tissue min‐1) and 3‐methylhistidine efflux was unchanged. In hypothyroid patients, neither tyrosine nor 3‐methylhistidine effluxes were significantly different from those in normal subjects. Whole body leucine flux (equivalent to appearance of leucine from protein breakdown) was significantly lower in both the thyrotoxic and hypothyroid patients compared with normal subjects (101 ± 7, 97 ± 7 and 133 ± 6 μmol leucine kg‐1 h‐1, respectively); however, even greater relative depressions were observed in removal of leucine from the free pool by non‐oxidative routes, i.e. by whole body protein synthesis (thyrotoxic, 56 ± 4, hypothyroid, 61 ± 4 and normal subjects, 89 ± 5 μmol leucine kg‐1 h‐1, respectively). After treatment of thyrotoxicosis and hypothyroidism whole body protein synthesis became normalized in both patient groups. The results suggest that derangement of thyroid function (with either an excess or a deficiency of thyroid hormone), leads to alterations of whole body leucine metabolism, probably reflecting alterations in tissue protein synthesis and breakdown, which are consistent with observed losses of body protein mass, and which reverse on treatment. The net loss of protein in thyrotoxic myopathy appears to be due more to a depression of muscle protein synthesis rather than to an increase in muscle protein breakdown.