Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on spanish men

Authors: LACLAUSTRA, MARTIN - National Center For Cardiovascular Research(CNIC); HURTADO-ROCA, LEDA YAMILEE - National Center For Cardiovascular Research(CNIC); SENDIN, MERCEDES - National Center For Cardiovascular Research(CNIC); LEON, MONTSERRAT - Aragon Institute; LEDESMA, MARTA - Aragon Institute; ANDRES, EVA - Centro De Investigacion Biomedica En Red (CIBER)-Epidemiología Y Salud Pública; FERNANDEZ-ORTIZ, ANTONIO - National Center For Cardiovascular Research(CNIC); GUALLAR, ELISEO - Johns Hopkins University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CASASNOVAS LENGUAS, JOSE ANTONIO - Aragon Institute

Submitted to: Nutrition, Metabolism and Cardiovascular Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2015
Publication Date: 9/25/2015
Citation: Laclaustra, M., Hurtado-Roca, L., Sendin, M., Leon, M., Ledesma, M., Andres, E., Fernandez-Ortiz, A.I., Guallar, E., Ordovas, J.M., Casasnovas Lenguas, J. 2015. Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on spanish men. Nutrition, Metabolism and Cardiovascular Diseases. 25:1095-1103.

Interpretive Summary: The thyroid gland influences almost all of the metabolic processes in the body. Subclinical thyroid conditions (i.e. normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels) may be associated with cardiovascular and metabolic risk. Given the difficulties in interpreting the thyroid-related biomarkers in relation to metabolic abnormalities, we investigated the relationship between metabolic syndrome and TSH in subjects with apparent normal thyroid function. We studied this in 3,533 male subjects with normal TSH and free T4 levels. Our results showed that TSH and free T4 within the normal range are associated with metabolic syndrome. People below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Technical Abstract: Background and aims: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. Methods and results: We studied 3533 male participants of the Aragon Workers Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. Conclusions: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.