This Article Full Text Full Text (PDF) All Versions of this Article: 90/7/4057    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Caraccio, N. Articles by Ferrannini, E. Search for Related Content PubMed PubMed Citation Articles by Caraccio, N. Articles by Ferrannini, E. Related Collections Thyroid Metabolism

Muscle Metabolism and Exercise Tolerance in Subclinical Hypothyroidism: A Controlled Trial of Levothyroxine

Department of Internal Medicine, and Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, University of Pisa School of Medicine, 56126 Pisa, Italy

Address all correspondence and requests for reprints to: Ele Ferrannini, M.D., Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. E-mail: ferranni{at}ifc.cnr.it.

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-T₄ replacement in a double-blind, randomized, placebo-controlled fashion.

Patients and Methods: We studied 23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO₂), carbon dioxide output, and heart rate were measured during incremental step-up exercise. Blood glucose, lactate, pyruvate, free fatty acid, glycerol, and ß-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-T₄-restored euthyroidism.

Results: 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 VO₂ 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-T₄ 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.

This article has been cited by other articles:

				P. Haentjens, A. Van Meerhaeghe, K. Poppe, and B. Velkeniers Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies Eur. J. Endocrinol., September 1, 2008; 159(3): 329 - 341. [Abstract] [Full Text] [PDF]

				B. Biondi and D. S. Cooper The Clinical Significance of Subclinical Thyroid Dysfunction Endocr. Rev., February 1, 2008; 29(1): 76 - 131. [Abstract] [Full Text] [PDF]