Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

Thyroid. 2016 Mar;26(3):347-55. doi: 10.1089/thy.2015.0345. Epub 2016 Feb 3.


Background: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition.

Methods: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry.

Results: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group (p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups (p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition.

Conclusions: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

Trial registration: ClinicalTrials.gov NCT00565864.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Antithyroid Agents / adverse effects
  • Antithyroid Agents / therapeutic use*
  • Biomarkers / blood
  • Body Composition / drug effects*
  • Calorimetry, Indirect
  • Case-Control Studies
  • Cross-Sectional Studies
  • Energy Intake
  • Energy Metabolism / drug effects*
  • Female
  • Hormone Replacement Therapy* / adverse effects
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / diagnosis
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / physiopathology
  • Middle Aged
  • Oxidation-Reduction
  • Surveys and Questionnaires
  • Thyrotropin / blood*
  • Thyroxine / adverse effects
  • Thyroxine / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Antithyroid Agents
  • Biomarkers
  • Thyrotropin
  • Thyroxine

Associated data

  • ClinicalTrials.gov/NCT00565864