Sadik Noha Adly, Rashed Laila Ahmed, El-Sawy Shereen Sadik
Internal Medicine Department, Diabetes and Endocrinology division, Faculty of Medicine, Cairo University, Cairo, Egypt.
Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Clin Med Insights Endocrinol Diabetes. 2022 Apr 21;15:11795514221093317. doi: 10.1177/11795514221093317. eCollection 2022.
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.
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.
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) ( < .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 ( < .001).
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.
显性和亚临床甲状腺功能减退大多与血脂异常相关,血脂异常是心血管疾病的重要危险因素。最近,研究发现促甲状腺激素(TSH)可通过增加肝脏前蛋白转化酶枯草溶菌素9型(PCSK9)的表达,对脂质代谢产生直接影响。PCSK9通过调节低密度脂蛋白胆固醇(LDL-C)水平在脂质代谢中发挥关键作用。因此,我们旨在评估新诊断的显性和亚临床甲状腺功能减退患者的循环PCSK9水平,并评估其与血清TSH和血脂的关系。
在本研究中,我们纳入了60例新诊断的未经治疗的显性和亚临床甲状腺功能减退患者,并选取30例甲状腺功能正常的受试者作为对照组。采用酶联免疫吸附测定(ELISA)试剂盒检测所有受试者的血清TSH、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、血脂谱和循环PCSK9水平。我们的数据采用均数±标准差或中位数和四分位数间距进行汇总。使用Spearman相关系数分析PCSK9表达水平与不同变量之间的相关性。
与对照组(3.30 ng/ml)相比,显性和亚临床甲状腺功能减退患者的循环PCSK9中位数水平显著升高(分别为12.45 ng/ml和7.50 ng/ml)(P<0.001)。在所有研究对象中,循环PCSK9水平与TSH、总胆固醇、甘油三酯和体重指数呈显著正相关,与FT4和FT3呈负相关。多元回归分析显示,TSH是循环PCSK9的唯一显著独立预测因子(P<0.001)。
我们的研究结果支持TSH通过与PCSK9的显著关联在脂质代谢中的新作用。TSH与PCSK9之间的这种关系是因果关系还是仅仅是一种关联,尚需进一步评估。