Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine.
BACKGROUND
Neuromuscular symptoms and impaired muscle energy metabolism have been described in subclinical hypothyroidism (sHT).


OBJECTIVE
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.


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.
Caraccio
Nadia
N
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.
Natali
Andrea
A
Sironi
Annamaria
A
Baldi
Simona
S
Frascerra
Silvia
S
Dardano
Angela
A
Monzani
Fabio
F
Ferrannini
Ele
E
D000328:Adult; D004311:Double-Blind Method; D015444:Exercise; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D013974:Thyroxine / Q000627:therapeutic use*
D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D013974:Thyroxine