CONTEXT: The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific 
adaptation of thyroid hormone levels in response to various conditions, such as 
hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle 
is intriguing because this enzyme could play a role in systemic as well as local 
T3 production.
OBJECTIVE: We determined D2 activity and D2 mRNA expression in human skeletal 
muscle biopsies under control conditions and during hypothyroidism, fasting, and 
hyperinsulinemia.
DESIGN: This was a prospective study.
SETTING: The study was conducted at a university hospital.
PATIENTS: We studied 11 thyroidectomized patients with differentiated thyroid 
carcinoma (DTC) on and after 4 wk off T4( replacement and six healthy lean 
subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h 
of fasting.
MEAN OUTCOME MEASURES: D2 activity and D2 mRNA levels were measured in skeletal 
muscle samples.
RESULTS: No differences were observed in muscle D2 mRNA levels in DTC patients 
on and off T4 replacement therapy. In healthy subjects, muscle D2 mRNA levels 
were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA 
expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 
activities were very low and not influenced by hypothyroidism and fasting.
CONCLUSION: Human skeletal muscle D2 mRNA expression is modulated by fasting and 
insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA 
modulation on the observed low D2 activities questions the physiological 
relevance of D2 activity in human skeletal muscle.