Endocrine Abstracts

Background: FGF21 is a critical metabolic regulator with beneficial effects on lipid and glucose metabolism. FGF21 is produced primarily by the liver and stimulates fatty acids oxidation, which prevents hepatic triglycerides accumulation and nonalcoholic fatty liver disease (NALFD). FGF21also increases insulin sensitivity and glucose uptake in adipose tissue. Paradoxically FGF21 is elevated in insulin resistance states e.g. NALFD, obesity and type 2 diabetes. It is not determined if it results from FGF21 resistance or compensatory increased secretion. In animals and in vitro studies thyroid hormones increase FGF21 secretion.

Aim: Investigate the association between circulating FGF21 and thyroid hormones, glucose and lipid metabolism in patients with hyper- and hypothyroidism

Methods: 57 hyperthyroid patients with Graves disease, 29 hypothyroid patients with autoimmune thyroid disease and 21 healthy controls were included. Additionally, a subset of 13 hyperthyroid patients was analyzed before, and after radioiodine treatment, in three different thyroid statuses typically occurring in this group – hyperthyroidism, hypothyroidism, and euthyroidism after l-thyroxin treatment. Serum FGF21 was measured with immunoassay.

Results: Serum FGF21 levels did not differ significantly in hyperthyroid and hypothyroid patients as compared with healthy subjects [median 100.30 (interquartile range, 59.61–191.93) and 141.50 (66.80–247.40) vs 78.50 (54.00–11.90) pg/ml P = 0.196 and 0.058 respectively]. In hyperthyroid patients treated with radioiodine, serum FGF21 level did not change in hyperthyroidism as compared with euthyroidism and hypothyroidism, however it has increased dramatically in hypothyroid phase compared with euthyroidism stage [102.30 (51.4–153.70) vs 199.30 (131.70–266) vs 70.80 (21.80–187.90) pg/ml, P = 0.999, P = 0.080 and P = 0.018 respectively]. In hyperthyroidism, there was no significant correlation between FGF21 serum levels and thyroid hormones, lipids, and glucose metabolism. In rapid onset hypothyroidism after radioiodine treatment, increased FGF21 serum levels correlated positively with triglycerides and cholesterol (Spearman coefficient rs = 0.46 and rs = 0.36 respectively) and correlated inversely with fT4 and SHBG (rs = −0.34 and rs = −0.41 respectively). In euthyroidism FGF21 serum levels correlated positively with insulin and HOMA index (rs = 0,49 and rs = 0.47) and correlated inversely with QUICKI index and SHBG (rs = −0.46 and rs = −0.51).

Conclusions: There was no stimulatory effect of thyroid hormones on FGF21 secretion. Circulating FGF21 rose markedly in rapidly developing hypothyroidism after radioiodine treatment and associated with the increase in triglycerides and cholesterol serum levels. In the critical metabolic state of lipid overload, FGF21 secretion may have a compensatory effect promoting lipid oxidation.