Effects of Altering Levothyroxine Dose on Energy Expenditure and Body Composition in Subjects Treated With LT4

J Clin Endocrinol Metab. 2018 Nov 1;103(11):4163-4175. doi: 10.1210/jc.2018-01203.


Background: It is unclear whether variations in thyroid status within or near the reference range affect energy expenditure, body mass, or body composition.

Methods: 138 subjects treated with levothyroxine (LT4) for hypothyroidism with normal TSH levels underwent measurement of total, resting, and physical activity energy expenditure; thermic effect of food; substrate oxidation; dietary intake; and body composition. They were assigned to receive an unchanged, higher, or lower LT4 dose in randomized, double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). The doses were adjusted every 6 weeks to achieve target TSH levels. Baseline measures were reassessed at 6 months.

Results: At study end, the mean LT4 doses and TSH levels were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 µg/kg (P < 0.001) and 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. No substantial metabolic differences in outcome were found among the three arms, although direct correlations were observed between decreases in thyroid status and decreases in resting energy expenditure for all subjects. The subjects could not ascertain how their LT4 dose had been adjusted but the preferred LT4 dose they perceived to be higher (P < 0.001).

Conclusions: Altering LT4 doses in subjects with hypothyroidism to vary TSH levels in and near the reference range did not have major effects on energy expenditure or body composition. Subjects treated with LT4 preferred the perceived higher LT4 doses despite a lack of objective effect. Our data do not support adjusting LT4 doses in patients with hypothyroidism to achieve potential improvements in weight or body composition.

Trial registration: ClinicalTrials.gov NCT00565864.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Body Composition / drug effects
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Energy Metabolism / drug effects
  • Female
  • Hormone Replacement Therapy / methods*
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / physiopathology
  • Male
  • Middle Aged
  • Reference Values
  • Thyroid Gland / metabolism*
  • Thyroid Gland / physiopathology
  • Thyroxine / administration & dosage*
  • Thyroxine / blood
  • Treatment Outcome


  • Thyroxine

Associated data

  • ClinicalTrials.gov/NCT00565864