Do early indicators of euthyroid sick syndrome predict later post-bariatric weight loss? Exploring a novel hypothesis

Despite bariatric surgery's success for most patients, up to 30 % do not experience optimal weight loss outcomes. Post-surgery weight loss outcomes are influenced by a complex interplay of factors that remain incompletely understood. Novel hypotheses are needed to identify putative predictors of suboptimal post-bariatric weight loss. Thyroid hormones, due to their important role in energy expenditure, have received study though research to date has not established clear associations between post-surgical weight loss and changes in standard thyroid markers. In contrast, research consistently documents a pattern similar to euthyroid sick syndrome (ESS) during severe caloric deprivation or fasting. ESS, an established response to periods of stress (e.g., critical illness, infection, famine) is believed to serve a protective function by suppressing metabolism and conserving weight. Defining features of ESS are: 1) TSH levels within normal range; 2) abnormally low levels of the metabolically active form of thyroid hormone, or free triiodothyronine (FT3); 3) abnormally high levels of the metabolically inactive reverse 3,3 ',5 '-triiodothyronine (rT(3)); and 4) abnormally low ratios of FT3 to rT(3). Low FT3/rT(3) ratio levels significantly predict survival outcomes in ESS. We present the novel hypothesis that: 1) severe hypocaloric dieting during the early post-surgical period may trigger an ESS-like syndrome; 2) development of ESS will be signaled by a decrease in the FT3/rT(3) ratio; and 3) early decreases in the FT3/rT(3) ratio will be associated with reduced weight loss at standard 1- and 2-year post-surgical follow-up visits. To examine whether preliminary data might support our hypothesis, we undertook a small exploratory study by collecting TSH, FT4, FT3, rT(3), and hypothyroid symptoms from adult patients undergoing Roux-en-Y gastric bypass (n = 12) or sleeve gastrectomy (n = 11). Body mass index was measured pre-surgery and 1- and 2-years post-surgery. Results showed reductions in the FT3:rT(3) ratio from pre- to early post-surgery significantly predicted reduced weight loss at 1 (p = 0.03) and 2 years (p = 0.02) post-surgery. No other thyroid-related markers nor symptoms were predictive. Replication with larger samples is needed, especially given our sizeable attrition at 1- and 2-year follow-up. In conclusion, our hypothesis that markers of ESS during the early post-surgical period would predict reduced longer-term weight loss was supported. If replicated in future, larger investigations, a practical application of this hypothesis-generating paper involves using the FT3:rT(3) ratio to identify post-bariatric patients at risk for longer-term suboptimal weight loss, potentially opening a key therapeutic window for therapeutic intervention (e.g., T-3 repletion).