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

Objective: To test whether increased protein breakdown occurs independently of other catabolic effects in mild experimental hyperthyroidism.

Design: Single blind, randomized, placebo controlled, crossover. 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 hour study in the basal state followed by a 3 hour euglycemic clamp study.

Setting: University clinical research unit.

Participants: Eight healthy women (24–46 years).

Intervention: 6 days thyroid hormone (thyroxine 50 µg and tri-iodothyronine 0.67 µg/kg/day) 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, glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans.