Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism

Alterations in muscle structure and function have been reported in overt hypothyroidism, with decreased activity of enzymes involved in anaerobic and oxidative glucose metabolism. To test whether similar changes in muscle energy metabolism are present in subclinical hypothyroidism (sHT), we studied 12 patients with sHT who complained of mild neuromuscular symptoms. The control group included 10 sex- and age-matched healthy volunteers. Skeletal muscle lactate and pyruvate production were determined in the resting state and during dynamic arm exercise. During exercise, blood lactate was significantly higher in sHT patients than in controls from the third exercise step onward (P = 0.02 at 30%, P = 0.008 at 40%, and P = 0.002 at 50% of maximal voluntary contraction). Moreover, the mean increment in blood lactate during exercise was positively related (r(2) = 0.44; P = 0.02) to the duration of sHT, but not to serum levels of TSH, free T-3, or free T4. No significant difference was found in blood pyruvate concentrations between the two groups at baseline or during exercise. Thus, the lactate/pyruvate ratio curve paralleled the lactate curve in patients as well as controls. We conclude that muscle energy metabolism is impaired in sHT in rough proportion to the known duration of the disease. Early L-T-4 therapy may be useful not only to provide specific treatment for such metabolic changes, but also to avoid progression to frank hypothyroidism.