The THYROID-HD (“A Randomized Controlled Trial of Thyroid Hormone Supplementation in Hemodialysis Patients”) is an NIH/NIDDK R01-supported double-blind randomized clinical trial that will determine the effects of levothyroxine vs. placebo on measures of health-related quality of life and physical performance (co-primary outcomes), as well as muscle strength, systolic function, and metabolic status (secondary outcomes) in hemodialysis patients with subclinical and high-normal thyrotropin levels (Principal Investigator: Dr. Connie M. Rhee).
Data spanning over three decades show that hypothyroidism is highly prevalent in the chronic kidney disease population, affecting ~25% of those receiving dialysis therapy. In the general population hypothyroidism, defined by elevated thyrotropin (TSH) levels, has been associated with impaired health-related quality of life and cardiovascular morbidity and mortality, but until recently there was a paucity of data regarding its prognostic implications in CKD. Our research has been the first to show a link between high-normal TSH levels and worse health-related quality of life Short Form 36 scores in hemodialysis patients, particularly among subscales centered on physical health (e.g., physical function, energy/fatigue). Our studies have also advanced the field by showing that mildly elevated TSH levels (>3.0mIU/L) are associated with heightened risk of cardiovascular disease and death across multiple dialysis cohorts. However, there remains considerable controversy as to 1) whether thyroid dysfunction is causally associated with adverse patient-centered and cardiovascular outcomes, and 2) if elevated TSH levels represent thyroid functional disease vs. non-thyroidal illness in CKD. While levothyroxine is one of the most commonly prescribed medications in chronic kidney disease, little is known about its efficacy in this population.
The objective of the study is to conduct a randomized double-blind placebo-controlled trial among hemodialysis patients with high-normal or subclinical hypothyroid range serum TSH levels to determine the effects of 24 weeks (i.e., 6 months) of levothyroxine vs. placebo on 1) health-related quality of life and 2) coronary artery calcification progression (co-primary endpoints).
As main secondary endpoints, we will also examine 1) health-related quality of life measured by the ThyPRO survey, 2) physical performance, 3) endothelial function, 4) vascular calcification inhibitor levels, and 5) total body fat percentage.
In a sub-study of hemodialysis patients, we will also examine exploratory secondary endpoints of 1) muscle strength, 2) systolic function, and 3) resting energy expenditure.