Body Composition, Insulin Resistance and Mediators of Appetite and Energy Homeostasis in Hyperthyroidism

Background: Hyperthyroidism is associated with reduced body weight despite an increase in appetite; due mainly to an increase in energy production. While appetite is regulated by the balance of orexogenic and anorexogenic peripheral signals like Ghrelin and Leptin respectively, energy expenditure is profoundly influenced by thyroxine itself as well as mediators like FGF 21 and Leptin. Hyperthyroidism offers a good model to study the impact of thyroid hormones on the above mediators. Materials & Methods: 35 adult patients with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, FGF21 levels & insulin resistance as well as the body composition by DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Results: Correction of hyperthyroidism was associated with an increase in body weight including both the lean body (p<0.001) and the fat mass (p<0.001), but with no change in percentage of total body fat (p=0.516). Accompanying the weight gain, there was no change in adiponectin (p=0.98), while a paradoxical decrease in insulin resistance was observed (p<0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 (p<0.001) and leptin levels (p=0.03) and an increase in ghrelin (p=0.05). Conclusion: Thyrotoxic state is associated with high leptin & FGF21 levels - both known to be thermogenic. Despite a lower weight and fat mass, thyrotoxicosis is associated with insulin resistance- possibly a direct effect of thyroxine. Ghrelin levels are low in thyrotoxicosis; which together with raised leptin is an unexpected finding, given the increased appetite observed in this condition.