Endocrine Abstracts

Background: Graves’ orbitopathy (GO) is an autoimmune orbital disease of insufficiently defined pathogenesis. Hyperlipidemia has been recognized as a risk factor for GO, while statin therapy may reduce its incidence. Since statins inhibit cholesterol synthesis, a potential link between cholesterol metabolism and the ocurence of GO is possible, but still unexplored. Alongside lipid-lowering, the anti-inflammatory effects of statins may also contribute to their beneficial impact on GO. Therefore, our study aims to investigate the patients’ basic lipid profiles, cholesterol synthesis and absorption status, and fatty acid content, all in relation to GO clinical phenotype.

Material and methods: The study included 89 consecutive patients with GO of varying degrees of activity and severity. We analyzed plasma concentrations of non-cholesterol sterols (NCS): cholesterol synthesis markers (desmosterol and lathosterol) and cholesterol absorption markers (campesterol, stigmasterol, and β-sitosterol) using a Gas Chromatography Flame-Ionization Detection (GC-FID) method. Lipid parameters were assessed in serum by routine biochemical methods on the Olympus AU400 analyzer. Fatty acids were also quantified in plasma using GC-FID (Agilent Technologies 7890A). Stimulating thyrotropin receptor antibodies (TSAb) were quantified using a cell-based bioassay (Thyretain®, Quidelortho, San Diego, CA, USA).

Results: The analysis of basic lipid parameters showed that patients with active GO had significantly lower HDL-C compared to inactive GO patients (P = 0.032). The ApoB/ApoA1 ratio was significantly higher in moderate-to-severe and sight-threatening GO (P = 0.029) and predicted the development of a more severe form of the disease (Or = 5.253, CI% (1.136-24.283), P = 0.034). Also, a positive correlation between LDL-C and TSAb levels (ρ=0.255, P = 0.019) was observed. Concerning NCS, there were no significant differences between groups, except for lathosterol, which exhibited a significant increase in more severe GO cases (P = 0.045). However, cholesterol synthesis-to-absorption ratio was significantly higher in patients with sight-threatening GO compared to patients with mild GO (P = 0.013). Furthermore, this ratio also showed a borderline-significant association with GO activity (P = 0.058) and positively correlated with CAS score (ρ=0.232, P = 0.048). Content of monounsaturated oleic fatty acid (18:1 n9) was significantly lower in active compared to inactive GO (P = 0.009). Oleic acid correlated negatively with CAS score (ρ=-0.241, P = 0.025) and TSAb (ρ=-0.245, P = 0.019).

Conclusions: Alterations of patients’ lipid profile and the status of cholesterol synthesis and absorption markers were associated with a worse clinical phenotype of GO. Furthermore, our results indicate the potentially protective role of oleic acid in GO pathogenesis.