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

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 7; pp. 4057 - 4062
• Main Authors: Caraccio, Nadia, Natali, Andrea, Sironi, Annamaria, Baldi, Simona, Frascerra, Silvia, Dardano, Angela, Monzani, Fabio, Ferrannini, Ele
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-07-2005
• Subjects: Adult; Biological and medical sciences; Double-Blind Method; Endocrinopathies; Exercise; Fatty Acids, Nonesterified - blood; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Hormone Replacement Therapy; Humans; Hypothyroidism - metabolism; Lactic Acid - blood; Male; Medical sciences; Muscle, Skeletal - metabolism; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oxygen Consumption - drug effects; Thyroid. Thyroid axis (diseases); Thyroxine - therapeutic use; Vertebrates: endocrinology; Endocrinopathy; Physical exercise; Thyroid diseases; Tolerance; Clinical trial; Muscle; Hypothyroidism; Metabolism; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-2344

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 β-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.