Body weight and waist circumference are differentially associated with the response to L-thyroxine treatment in primary hypothyroidism.

Background: Thyroid hormones (TH) and neurotransmitter orexin (ORX) are implicated in the regulation of metabolism. Abdominal weight gain is common in primary hypothyroidism (PH). Methods: Our aim was to investigate whether TH affected peripheral weight gain, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C), before and 6 months after L-thyroxine substitution therapy. A secondary aim was to investigate the role of ORX. Results: Weight gain was positively correlated with improvement in QoL (r = 0.72, p = 0.003) and with CSF ORX levels in the 15 included patients (r = 0.78, p = 0.001). Increased WC, which was not associated with QoL changes, correlated negatively with free thyroxine levels, after 6 months of treatment, in both CSF (r = -0.71, p = 0.003) and serum (r = -0.64, p = 0.0097). Increased LDL-C correlated negatively with CSF free thyroxine levels after 6 months of treatment (r = -0.74, p = 0.003). Conclusion: The marked correlations with CSF levels of thyroxine and ORX suggest that hypothalamic mechanisms participate in the regulation of WC and weight during L-thyroxine therapy, highlighting the need for individualized treatment of the metabolic disturbances seen in PH. Short communication: Through evaluating the dynamics of body weight and waist circumference during the initial treatment of primary hypothyroidism, a positive correlation was found between orexin levels in CSF and the change in body weight. Furthermore, negative correlations were found between CSF free thyroxine levels and the changes in waist circumference and serum LDL-C levels. These findings emphasize the importance of finding future individualized treatment strategies in primary hypothyroidism, particularly regarding metabolic disturbances.