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Effect of l-Thyroxine Replacement Therapy on Surrogate Markers of Skeletal and Cardiac Function in Subclinical Hypothyroidism

Christ-Crain, Mirjam MD*; Meier, Christian MD†; Huber, Peter R. PhD‡; Staub, Jean-Jacques MD§; Müller, Beat MD¶

CME Review Article #19
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Abstract: Overtly impaired thyroid function affects skeletal and cardiac muscle function, reflected in increased circulating skeletal muscle enzyme levels (ie, creatine kinase [CK] and myoglobin [Mb]), prolonged ankle reflex time (ART), and altered systolic time intervals (STI). The response of these markers of muscular function to l-T4 replacement therapy in patients with subclinical hypothyroidism was evaluated in a prospective, double-blind study. Sixty-six women with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 12.9 ± 8.2 mU/L) were randomly assigned to receive l-thyroxine or placebo for 48 weeks. Sixty-three of the 66 women completed the study. Mb, CK, ART, and STI were measured at baseline and 48 weeks after l-thyroxine or placebo treatment, respectively. In patients with markedly elevated TSH levels at baseline (>12 mU/L), the ART decreased significantly after 48 weeks of l-thyroxine treatment (P = 0.01). There was no treatment effect on circulating CK or Mb levels. The STI were not altered in subclinical hypothyroidism and consequently remained unchanged by l-thyroxine treatment. ART is significantly reduced after l-T4 replacement therapy in patients with markedly elevated TSH levels at baseline. CK and Mb, representing surrogate markers of muscle function, as well as systolic cardiomuscular function, assessed by measurement of resting left ventricular systolic function, are not affected in subclinical hypothyroidism. This suggests a mildly affected, yet compensated neuromuscular dysfunction. Of various potential surrogate markers of muscular function, ART seems to reflect best the subtle changes of mild thyroid failure.

*Fellow, †Senior Registrar, §Emeritus Professor, ¶Associate Professor, Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Internal Medicine and ‡Full Professor, Department of Central Laboratories, University Hospitals, Basel, Switzerland.

Supported by grants from the Swiss National Science Foundation (32.27866.89, 32.37792.93, and 32.37792.98) and unconditional research grants from Henning Berlin, Novartis, Roche Research, Nora van Meeuwen-Häfliger, and Krokus Foundations and the “Sonderprogramm zur Förderung des akademischen Nachwuchses der Universität Basel” (to BM).

The authors have disclosed that they have no significant relationships with or financial interests in any commercial company that pertains to this educational activity.

Reprints: Mirjam Christ-Crain, MD, Division of Endocrinology, Department of Internal Medicine, University Hospitals, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: christmj@bluewin.ch.

Chief Editor’s Note: This article is the 19th of 36 that will be published in 2004 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned precede the CME Examination at the back of this issue.

© 2004 Lippincott Williams & Wilkins, Inc.