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 serum thyroxine (T4) and triiodothyronine (T3) levels.

Participants: 9,981 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 ∽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 BMI despite report of consuming less calories/day/kg; were more likely to be taking beta-blockers, statins, and anti-depressants; 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 HDL and lower serum LDL, triglycerides, and CRP. Age was associated with serum free T3:free T4 ratio in all participants; caloric intake was 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.

Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

Peterson S, McAninch EA, Bianco AC. J. Clin Endocrinol. Metab. Oct 4, 2016. PMID: 27700539

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