Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men

Abstract

Objective: Thyroid disorders affect metabolism and body composition. Existing literature has been conflicting on whether this is also the case for thyroid hormone levels within the euthyroid range. Therefore, we have investigated the relationship between thyroid hormone concentrations and body composition together with metabolic parameters in a population of healthy euthyroid men. Methods: Healthy male siblings (nZ941, 25-45 years, median BMI 24.6) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid autoimmunity were exclusion criteria. Body composition and muscle cross-sectional area were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Total (triiodothyronine (T 3 ; TT 3 ) thyroxine and (T 4 ; TT 4 )) and free thyroid hormones (FT 3 and FT 4 ), TSH, and reverse T 3 (rT 3 ) and thyroid-binding globulin (TBG) were determined using immunoassays. Results: BMI was positively associated with (F)T 3 (P!0.0001). Whole body fat mass displayed positive associations with TT 3 and with (F)T 4 and TBG (P%0.0006). Positive associations were further observed between leptin and (F)T 3 , TT 4 , and TBG (P%0.0002). Inverse associations between lean mass and muscle cross-sectional area and (F)T 3 , (F)T 4 , and TBG were observed (P%0.0003). Higher levels of (F)T 3 and TBG were associated with lower insulin sensitivity, assessed by homeostatic model assessment of insulin resistance (IR; P%0.0001). No associations between TSH and body composition or metabolic parameters were seen. Conclusion: We show that a less favorable body composition (with higher fat and lower muscle mass and accompanying higher leptin concentrations) and IR are associated with higher thyroid hormone levels in healthy young men with well characterized euthyroidism.

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

“…Interdependency between serum leptin and TH concentrations is assumed to be mediated by a complex interplay with TSH, further involving thyrotropin-releasing hormone (46,47). In concordance, a recent study on young men provided evidence for a link between serum TSH and leptin concentrations, even in the euthyroid state (48). In recognition of these results, we tested for a possible effect of TSH on the association between 3,5-T2 and leptin.…”

Thyrotropin Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents

“…Given the role of thyroid hormones in the regulation of energy expenditure and thermogenesis (40), and the increasingly well-established relations between subtle alterations in TSH, thyroid hormone levels, and cardiometabolic risk factors (13,(17)(18)(19)(20)(21)23,24,28,29,35), there has been interest in assessing the effects of weight loss on thyroid hormone levels. In a study of adult overweight or obese otherwise healthy subjects undergoing a controlled lifestyle modification program, modest weight loss (6.5 -1.0%) resulted in reductions in TT3 without significant changes in TSH or fT4.…”

“…The present assessment of an unselected U.S. population (by default devoid of specific clinical indications for testing) minimizes the risk of selection bias. While other published analyses of population databases have not addressed any potential racial or ethnic differences (10,11,(17)(18)(19)21,(23)(24)(25)28,29), this NHANES cohort consisted of participants who predominantly selfidentified as non-Hispanic white, non-Hispanic black, Mexican-American, or other Hispanic. The lack of any race/ ethnicity differences in TSH and thyroid hormones suggests that with respect to race/ethnicity, other factors such as BMI (which did show ethnicity differences in the analysis) still play a greater role than the thyroid axis in determining overall cardiometabolic risk.…”

“…As a consequence, there has been increasing interest in determining if additional serum parameters of thyroid function may better inform assessments of thyroid hormone activity at the tissue level (16). Free thyroxine (fT4) has been negatively correlated with components of metabolic syndrome (17,18), while higher free triiodothyronine (fT3) has been related to increased waist circumference (19) and BMI (19,20) but lower insulin sensitivity (21). The ratio of T3 to T4 (or fT3 to fT4) has been proposed as a better estimate of tissuespecific deiodinase activity in the conversion of T4 to T3 (22).…”

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

“…This suggests an individual set point for pituitary-thyroid axis function (1). We and others have shown that this between-subject variation in TH levels, although within the normal range, is nevertheless associated with a number of clinical parameters such as bone mass, BMI, metabolic indices, and heart rate (2,3,4,5). The physiological basis of the set point of this axis is poorly understood (6).…”