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Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine.

Author(s): Caraccio N, Natali A, Sironi A, Baldi S, Frascerra S, Dardano A, Monzani F, Ferrannini E

Affiliation(s): Department of Internal Medicine, and Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, University of Pisa School of Medicine, Via Roma 67, 56126 Pisa, Italy.

Publication date & source: 2005-07, J Clin Endocrinol Metab., 90(7):4057-62. Epub 2005 Apr 26.

Publication type: Clinical Trial; Randomized Controlled Trial

BACKGROUND: Neuromuscular symptoms and impaired muscle energy metabolism have been described in subclinical hypothyroidism (sHT). AIM: The 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 L-T(4) replacement in a double-blind, randomized, placebo-controlled fashion. PATIENTS AND METHODS: We studied 23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO(2)), carbon dioxide output, and heart rate were measured during incremental step-up exercise. Blood glucose, lactate, pyruvate, free fatty acid, glycerol, and beta-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 L-T(4)-restored euthyroidism. RESULTS: Maximal power output (P = 0.02) and VO(2) max (P = 0.04) were reduced in sHT, and, with increasing workload, patients achieved higher heart rates (P < 0.03) at VO(2) values equivalent to 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 free fatty acid 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-T(4) replacement, while improving neuromuscular symptoms, did not produce significant changes in the energy or substrate response to exercise. CONCLUSIONS: The response to exercise is altered both in terms of tolerance and pattern of substrate utilization in sHT patients. Restoring stable euthyroidism does not correct this defect over a 1-yr period.

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