The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

Abstract

Introduction: Overt and subclinical hypothyroidism are mostly associated with dyslipidemia, an essential cardiovascular risk factor. Recently, thyroid stimulating hormone (TSH) was identified to have a direct role on lipid metabolism via increased expression of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 plays a crucial role in lipid metabolism via regulating LDL-C levels. Thus, we aimed to evaluate circulating PCSK9 levels and to assess its relationship with serum TSH and lipids in newly diagnosed patients had overt and subclinical hypothyroidism. Methods: In our study, we enrolled 60 newly diagnosed untreated patients with overt and subclinical hypothyroidism and 30 euthyroid subjects served as the control group. Serum TSH, FT4, FT3, lipid profile and circulating PCSK9 levels using ELISA kits were measured in all subjects. Our data were summarized using mean ± SD or median and interquartile range. Correlations between PCSK9 expression levels and different variables were done using Spearman correlation coefficient. Results: Circulating PCSK9 median levels were significantly increased in patients had overt and subclinical hypothyroidism (12.45 ng/ml, 7.50 ng/ml respectively) compared to the control group (3.30 ng/ml) ( P < .001). Circulating PCSK9 levels significantly correlated positively with TSH, total cholesterol, triglycerides, and BMI, and negatively correlated with FT4 and FT3 among all studied subjects. Using multivariate regression analysis TSH was the only significant independent predictor of circulating PCSK9 ( P < .001). Conclusion: Our results supports the new implication of TSH in lipid metabolism via the significant association with PCSK9. Whether this relationship between TSH and PCSK9 is a cause or just an association needs further evaluation.