• A major concern for patients with primary hypothyroidism is metabolic changes, and a common misconception is that weight changes are the primary metabolic alteration, when changes in abdominal fat and cholesterol are more important. • Patients with primary hypothyroidism and measurements of metabolic factors, cerebrospinal fluid levels of thyroid hormones and orexin, and Quality of Life assessments were followed before treatment initiation and after in median 6 months of treatment. • Thyroid hormones regulate changes in abdominal fat and cholesterol metabolism in part by affecting the ventromedial nucleus in hypothalamus. In the present study, changes in abdominal waist circumference and LDL levels were correlated with levels of thyroxine in cerebrospinal fluid after initiating L-thyroxine supplementation. • The thyroid hormone system influences the orexin system. In the present study, changes in body weight (but not abdominal changes) were correlated with orexin levels prior to L-thyroxine supplementation. In addition, patients with a positive weight change scored higher on the quality of life assessments. • The supply of thyroxine in the hypothalamic area and the orexin-system are both important regulators of abdominal fat for the former, and physical activity and muscle mass for the latter system. Thyroid hormones (TH) and neurotransmitter orexin (ORX) are implicated in the regulation of metabolism. Abdominal weight gain is common in primary hypothyroidism (PH). 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. 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). 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. 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.
Funkquist et al. (Wed,) studied this question.