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

Author:

Ettleson Matthew D1ORCID,Penna Gustavo C E1,Wan Wen2,Benseñor Isabela M3,Laiteerapong Neda2ORCID,Bianco Antonio C1ORCID

Affiliation:

1. Section of Endocrinology, Diabetes, and Metabolism, University of Chicago , Chicago, IL 60637 , USA

2. Section of General Internal Medicine, University of Chicago , Chicago, IL 60637 , USA

3. Center for Clinical and Epidemiological Research, Clinical Hospital, Department of Medicine, University of Sao Paulo , Sao Paulo, 05508-000 , Brazil

Abstract

Abstract Context Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. Objective This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. Methods Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. Results From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as 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. Notably, the average baseline LT4 dose was lowest in the high–high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. Conclusion GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Funder

National Institute of Diabetes and Digestive and Kidney Disease

National Institutes of Health

Diabetes Research and Training Center

University of Chicago

Brazilian Ministry of Health

Brazilian National Research Council

FAPESP

Publisher

The Endocrine Society

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