Neuromuscular symptoms and impaired muscle energy metabolism have been described in subclinical hypothyroidism (sHT). Aim of the study was to evaluate the energy and substrate response to exercise in sHT patients using a standardized protocol, and to test the effect of LT₄ replacement in a double blind, randomized, placebo-controlled fashion. We studied 23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO₂), carbon dioxide output (VCO₂), and heart rate were measured during incremental step-up exercise. Blood glucose, lactate, pyruvate, FFA, glycerol, and -hydroxybutyrate concentrations were measured at rest, every 2 min during exercise, and during 20 min of recovery. The exercise protocol was repeated after 6 months of placebo or LT₄-restored euthyroidism. Maximal power output (P = 0.02) and VO₂ max (P = 0.04) were reduced in sHT and, with increasing workload, patients achieved higher heart rates (P < 0.03) at equivalent VO₂'s as those of controls. The respiratory quotient increments were significantly higher in patients than controls (P < 0.04). Blood lactate and pyruvate, and their ratio rose with a steeper slope (P < 0.0001, P < 0.001, and P < 0.01, respectively) in patients than controls. Resting plasma FFA and blood glycerol levels were significantly higher in patients than controls (P < 0.0003 and P < 0.003, respectively) throughout baseline, exercise, and recovery. L-T₄ replacement, while improving neuromuscular symptoms, did not produce significant changes in the energy or substrate response to exercise.

We conclude that, in sHT the response to exercise is altered both in terms of tolerance and pattern of substrate utilization. Restoring stable euthyroidism does not correct this defect over a one-year period.