title: Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown.
abstract: 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 [2H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was increased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (microg.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 (microg.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.
authors.affiliation: Medical Dept. M, Aarhus Univ. Hospital, DK-8000 Aarhus C, Denmark. anne.lene.riis@ki.au.dk
authors.forename: Anne Lene Dalkjaer
authors.initials: AL
authors.lastname: Riis
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Signe
authors.initials: S
authors.lastname: Gjedde
authors.forename: Helene
authors.initials: H
authors.lastname: Nørrelund
authors.forename: Anne Grethe
authors.initials: AG
authors.lastname: Jurik
authors.forename: K S
authors.initials: KS
authors.lastname: Nair
authors.forename: Per
authors.initials: P
authors.lastname: Ivarsen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Weeke
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001823:Body Composition; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000502:physiology*; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy / Q000378:metabolism*; D007700:Kinetics; D008713:Methimazole / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009587:Nitrogen Isotopes; D010649:Phenylalanine / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D009124:Muscle Proteins; D009587:Nitrogen Isotopes; D013963:Thyroid Hormones; D010649:Phenylalanine; D008713:Methimazole