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Increased Protein Turnover and Proteolysis Is an Early and Primary Feature of Short-Term Experimental Hyperthyroidism in Healthy Women

Medical Department M (Diabetes and Endocrinology) (A.L.D.R., J.O.L.J., J.F., J.W., N.M.), Aarhus University Hospital, and Institute of Experimental Clinical Research (P.I., J.F., N.M.), Aarhus University, 8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Anne Lene Riis, Medical Department M, Aarhus University Hospital, 8000 Aarhus C, Denmark. E-mail: anne.lene.riis{at}ki.au.dk.

Context: Hyperthyroidism increases energy expenditure, glucose turnover, lipolysis, and protein breakdown.

Objective: Our objective was to test whether increased protein breakdown occurs independently of other catabolic effects in mild experimental hyperthyroidism.

Design: We conducted a single-blind, randomized, placebo-controlled, crossover study. Protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique ([¹⁵N]phenylalanine and [²H₄]tyrosine). All subjects underwent a 3-h study in the basal state followed by a 3-h euglycemic clamp study.

Setting: The study took place at a university clinical research unit.

Participants: Eight healthy women (24–46 yr old) participated.

Intervention: Intervention included 6 d thyroid hormone (T₄ 50 µg and T₃ 0.67 µg/kg·d) or placebo administration.

Results: Thyroid hormone administration led to mild T₃ hyperthyroidism with more than a doubling of T₃ levels and suppression of TSH. Energy expenditure and body composition was unchanged. Glucose infusion rates, forearm glucose uptake, and levels of lipid intermediates were also alike. Basal whole-body phenylalanine flux and tyrosine flux (reflecting whole-body protein breakdown) were increased (P < 0.05) as were whole-body protein synthesis rate (P = 0.05). Basal forearm rate of appearance and disappearance for phenylalanine (reflecting muscle protein breakdown and synthesis) were similar.

Conclusions: Mild short-term experimental hyperthyroidism increases whole-body protein turnover and breakdown before any measurable changes in energy expenditure or glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans.