FRI488 The Effect Of Thyroid Stimulating Hormone On Brown Adipose Tissue In Humans
Authors: Salej Laura , Kodani Sean D , Chaves Natalia , Youssef Kerolos N , Monahan-Earley Rita , Halle Hall , Shaelah Huntington , Annie Pierce , Parker John A , Cypess Aaron M , Kolodny Gerald , Tseng Yu-Hua , James Benjamin C , Gavrila-Filip Alina 
Published: October 2023

Abstract
Disclosure: L. Salej: None. S.D. Kodani: None. N. Chaves: None. K.N. Youssef: None. R. Monahan-Earley: None. H. Halle: None. H. Shaelah: None. P. Annie: None. J.A. Parker: None. A.M. Cypess: None. G. Kolodny: None. Y. Tseng: None. B.C. James: None. A. Gavrila-Filip: None.
Obesity and diabetes are two main public health concerns due to their high impact on global morbidity and mortality. In an effort to find new treatment strategies, highly active metabolic tissues such as brown adipose tissue (BAT) have been studied as potential targets. Animal studies have shown that TSH may have a direct local effect on BAT mass and activity by stimulating local T3 production via increased deiodinase-2 (DIO2) expression and also by increasing the expression of uncoupling protein-1 (UCP-1), the key molecule in BAT thermogenesis. We hypothesized that high circulating TSH levels could increase BAT activity by increasing local T3 production and generating a local tissue "thyrotoxicosis". We studied 7 patients with thyroid cancer who underwent thyroid surgery and required recombinant TSH (rhTSH) administration for standard follow-up procedures. Each patient underwent 2 PET-CT scans for assessment of BAT volume and activity, first one day after the rhTSH administration (high TSH state) and then 1-3 months later on suppressive thyroid hormone (TH) treatment (low TSH state). Indirect calorimetry and serum thyroid function tests, fasting glucose, insulin, HbA1c, and lipid panel were measured. Our results show that there was a statistically significant difference in TSH levels (p = 0.0095), with stable circulating T4 and T3 between the low and high TSH states. There was no statistically significant difference in the BAT volume and activity (SUVmax) between the high TSH and low TSH states. Age was a significant predictor of BAT SUVmax (p = 0.008; coeff = -0.39, CI = -0.65-0.13), while BMI was a significant predictor for resting energy expenditure (REE) (p = 0.04; coeff = -203.95, CI = -396.12 - -10.78). Based on these findings, along with those from our previous study[1] showing that circulating TH levels may not be directly correlated with BAT function, we have extended our study to assess the intracellular thyroid hormone status in BAT. We have collected deep peri-thyroidal adipose tissue and subcutaneous white adipose tissue (WAT) as a control group from patients undergoing thyroid surgery. In these samples, we will measure mRNA expression of TSH receptors, TH receptors, β-adrenergic receptors, DIO2 and UCP-1 and evaluate for correlations with circulating TSH and TH levels as well as different metabolic parameters to get a deeper insight into BAT function in humans.
Reference: 1. Gavrila A et al. Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status. Thyroid. 2017 Jan 1;27(1):1-10.
Presentation: Friday, June 16, 2023