TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Growth mixture modeling identified 4 distinct TSH trajectory classes in levothyroxine-treated participants.

• 621 LT4-treated study participants from the ELSA-Brasil cohort were analyzed.
• The best-fit GMM approach using latent class growth analysis (LCGA) identified 4 classes.
• Classes were defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH.
• The GMM/LCGA methodology used serial TSH measurements from a large prospective longitudinal study.

The high-high normal TSH group had the lowest average baseline levothyroxine dose compared to other trajectory classes.

• The average baseline LT4 dose in the high-high normal TSH group was 77.7 µg.
• This difference was statistically significant (P < .001) compared to the other classes.
• This finding suggests that lower LT4 dosing is associated with consistently higher-normal TSH levels over time.

There were no significant differences in cardiovascular health markers between the TSH trajectory classes at baseline.

• Baseline cardiovascular markers assessed included blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization.
• The absence of baseline differences indicates that trajectory class differences in CV markers emerged over the study period rather than being pre-existing.
• Repeated measure analyses were used to assess within-class changes over time.

The low to normal TSH class showed significant increases in multiple cardiovascular metabolic markers over the study period.

• Total cholesterol increased significantly (P = .049) in the low to normal TSH class.
• High-density lipoprotein cholesterol increased significantly (P < .001).
• Triglycerides increased significantly (P < .001).
• Hemoglobin A1c increased significantly (P = .001).
• This class was highlighted as having the most notable pattern of CV marker changes.

At least one significant difference in cardiovascular markers occurred in all four TSH trajectory classes over the study period.

• Changes were observed across blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization.
• Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes.
• Repeated measure analyses were used to assess within-class changes in CV health markers.
• The finding applied universally across all 4 trajectory classes regardless of TSH pattern.

GMM/LCGA was demonstrated as a viable proof-of-principle approach for classifying LT4 treatment adequacy using TSH trajectory analysis.

• This study was described as 'a proof of principle study' using longitudinal clinical data from a large prospective cohort.
• The authors note that 'more comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.'
• The ELSA-Brasil cohort provided the longitudinal thyroid hormone level data needed for trajectory classification.
• TSH trajectory classification is described as 'a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time.'