Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors.

Purpose: Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors.

Methods: In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed.

Results: SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09).

Conclusions: Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.