Analysis of non-cholesterol sterols and fatty acids in patients with graves’ orbitopathy: insights into lipid metabolism in relation to the clinical phenotype of disease

Abstract

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.