Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy

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Abstract
Context Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism. Objective To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE) Design Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center between January 2013 and July 2019. Patients 649 non-diabetic women with BMI > 30 kg/m2 and TSH level within 0.4-4.0 mU/l were segregated in two groups: patients with primary hypothyroidism in LT4 therapy (n=85) and patients with normal thyroid function (n=564). Main outcomes REE and body composition assessed using indirect calorimetry and bioimpedance. Results REE was reduced in women with hypothyroidism in LT4 therapy when compared to controls (28.59±3.26 vs. 29.91±3.59 kcal/Kg FFM/die), also when adjusted for age, BMI, body composition, level of physical activity (p=0.008). This metabolic difference was attenuated only when adjustment for HOMA-IR was performed. Conclusions This study demonstrated that obese hypothyroid women in LT4 therapy with normal serum TSH level compared to euthyroid controls, are characterized by reduced REE, in line with the hypothesis that standard LT4 replacement therapy may not fully correct metabolic alterations related to hypothyroidism. We are not able to exclude that this feature may be influenced by the modulation of insulin sensitivity at the liver site, induced by LT4 oral administration.

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