Is a Normal TSH Synonymous With "Euthyroidism" in Levothyroxine Monotherapy?

J Clin Endocrinol Metab. 2016 Dec;101(12):4964-4973. doi: 10.1210/jc.2016-2660. Epub 2016 Oct 4.


Context: Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism.

Objective: To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status.

Design: Cross-sectional data from the US National Health and Nutrition Examination Survey (2001-2012) was used to evaluate 52 clinical parameters. LT4 users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with T4 and T3 levels.

Participants: A total of 9981 participants with normal serum TSH were identified; 469 were LT4-treated.

Results: Participants using LT4 had higher serum total and free T4 and lower serum total and free T3 than healthy or matched controls. This translated to approximately 15-20% lower serum T3:T4 ratios in LT4 treatment, as has been shown in other cohorts. In comparison to matched controls, LT4-treated participants had higher body mass index despite report of consuming fewer calories/day/kg; were more likely to be taking beta-blockers, statins, and antidepressants; and reported lower total metabolic equivalents. A serum TSH level below the mean in LT4-treated participants was associated with a higher serum free T4 but similar free and total T3; yet those with lower serum TSH levels exhibited higher serum high-density lipoprotein and lower serum low-density lipoprotein, triglycerides, and C-reactive protein. Age was negatively associated with serum free T3:free T4 ratio in all participants; caloric intake was positively associated in LT4-treated individuals.

Conclusions: In a large population study, participants using LT4 exhibited lower serum T3:T4 ratios and differed in 12/52 objective and subjective measures.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Health Surveys
  • Humans
  • Hypothyroidism / blood*
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Thyroid Function Tests
  • Thyrotropin / blood*
  • Thyroxine / blood*
  • Thyroxine / therapeutic use*
  • Triiodothyronine / blood*


  • Triiodothyronine
  • Thyrotropin
  • Thyroxine