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

Context: Levothyroxine (LT ₄ ) monotherapy is the standard of care for hypothyroidism.
Objective: To determine whether LT ₄ 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. LT ₄ users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with T ₄ and T ₃ levels.
Participants: A total of 9981 participants with normal serum TSH were identified; 469 were LT ₄ -treated.
Results: Participants using LT ₄ had higher serum total and free T ₄ and lower serum total and free T ₃ than healthy or matched controls. This translated to approximately 15-20% lower serum T ₃ :T ₄ ratios in LT ₄ treatment, as has been shown in other cohorts. In comparison to matched controls, LT ₄ -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 LT ₄ -treated participants was associated with a higher serum free T ₄ but similar free and total T ₃ ; 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 T ₃ :free T ₄ ratio in all participants; caloric intake was positively associated in LT ₄ -treated individuals.
Conclusions: In a large population study, participants using LT ₄ exhibited lower serum T ₃ :T ₄ ratios and differed in 12/52 objective and subjective measures.