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

Abstract

Levothyroxine (LT₄) monotherapy is the standard of care for hypothyroidism. To determine whether LT₄ at doses that normalize the serum TSH is associated with normal markers of thyroid status. 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. A total of 9981 participants with normal serum TSH were identified; 469 were LT₄-treated. 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. In a large population study, participants using LT₄ exhibited lower serum T₃:T₄ ratios and differed in 12/52 objective and subjective measures.