The impact of the metabolic phenotype on thyroid function in obesity

Paolo Marzullo, Chiara Mele, Stefania Mai, Gabriele Guzzaloni, Davide Soranna, Maria Antonella Tagliaferri, Maria Elisa Berselli, Flavia Prodam, Daniela Surico, Gianluca Aimaretti, Massimo Scacchi

Obesity is known to promote mild hyperthyrotropinaemia by unknown metabolic mechanisms. This investigation aimed to explore the association between thyroid function and metabolic phenotype in euthyroid obese individuals. Retrospective, cross-sectional study. Tertiary care center. 952 euthyroid obese individuals referred to our Institution for obesity. Serum levels of TSH, FT4, glucose, insulin and HbA1c levels, lipid profile, liver function and proinflammatory indices were measured. Resting energy expenditure was assessed by indirect calorimetry and body composition by bioimpedance analysis. On admission, 306 patients had previously diagnosed diabetes mellitus on treatment with metformin, while 113 patients were diagnosed with incident diabetes mellitus. Serum TSH levels were similar between metformin-treated diabetic subjects and metformin-untreated subjects, while FT4 was slightly but significantly higher in the former. Analysis stratified by TSH categories found no effect of metformin-treated diabetes mellitus on TSH levels. Interestingly, obese patients with incident diabetes showed lower TSH levels than normoglycaemic ones. In correlation studies on the whole dataset, an association related TSH to BMI and total cholesterol levels, which was lost upon adjustment for individual confounders. FT4 levels were found to be inversely related to BMI, insulin resistance and triglycerides, while being directly associated with HDL-cholesterol levels. These correlations remained unaltered after controlling for individual confounders. In multivariate linear regression analysis, TSH was associated with FT4, total cholesterol and BMI values. Significant predictors of FT4 were constituted by previously diagnosed diabetes mellitus, BMI, TSH and age. In euthyroid obese subjects, FT4 seems more closely related than TSH levels to parameters of cardiometabolic risk. TSH levels did not differ between metformin-treated and untreated subjects, while they were lower in patients with incident diabetes mellitus compared to normoglycaemic ones.