Thyroid Function Variation in the Normal Range, Energy Expenditure, and Body Composition in L-T4–Treated Subjects

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 7; pp. 2533 - 2542
• Main Authors: Samuels, Mary H., Kolobova, Irina, Antosik, Megan, Niederhausen, Meike, Purnell, Jonathan Q., Schuff, Kathryn G.
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.07.2017; Oxford University Press
• Subjects: Absorptiometry, Photon - methods; Adipose tissue; Adult; Aged; Anthropometry; Body composition; Body Composition - drug effects; Body fat; Body mass index; Body weight; Clinical s; Cross-Sectional Studies; Energy; Energy expenditure; Energy Metabolism - drug effects; Exercise - physiology; Female; Food intake; Humans; Hypothyroidism; Hypothyroidism - diagnosis; Hypothyroidism - drug therapy; Laboratories; Male; Middle Aged; Nutrient deficiency; Oxidation; Physical activity; Reference Values; Severity of Illness Index; Thyroid Function Tests; Thyroid gland; Thyroid hormones; Thyroid-stimulating hormone; Thyroxine; Thyroxine - administration & dosage; Triiodothyronine; Variation; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2017-00224

Purpose:It is not clear whether upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. Thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition, and therefore clinically relevant variations in these parameters may occur across the normal range of thyroid function.Methods:This was a cross-sectional study of 140 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (L-T4) who had TSH levels across the full span of the laboratory reference range (0.34 to 5.6 mU/L). Subjects underwent detailed tests of energy expenditure (total and resting energy expenditure, thermic effect of food, physical activity energy expenditure), substrate oxidation, diet intake, and body composition.Results:Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ in any of the outcome measures. However, across the entire group, serum free triiodothyronine (fT3) levels were directly correlated with resting energy expenditure, body mass index (BMI), body fat mass, and visceral fat mass, with clinically relevant variations in these outcomes.Conclusions:Variations in thyroid function within the laboratory reference range have clinically relevant correlations with resting energy expenditure, BMI, and body composition in L-T4–treated subjects. However, salutary effects of higher fT3 levels on energy expenditure may be counteracted by deleterious effects on body weight and composition. Further studies are needed before these outcomes should be used as a basis for altering L-T4 doses in L-T4–treated subjects.In hypothyroid subjects receiving L-T4 therapy with normal TSH levels, fT3 levels were directly correlated with BMI, body adiposity, and resting, but not total, energy expenditure.