BACKGROUND: Effects of thyroid function status on lipoprotein metabolism may 
extend into the euthyroid range. Low-density lipoprotein (LDL) metabolism is 
governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which 
down-regulates LDL receptor expression, resulting in higher LDL cholesterol 
(LDL-C). Here, we tested whether plasma PCSK9 correlates with thyroid function 
in nonobese and obese euthyroid subjects.
METHODS: We assessed the extent to which plasma PCSK9 is determined by 
thyrotropin (TSH) in 74 euthyroid subjects (31 women; TSH between 0.5 and 
4.0 mU/L and free thyroxine [FT4] between 11.0 and 19.5 pM) with varying degrees 
of obesity (body mass index [BMI] ranging from 20.2 to 40.4 kg/m(2)).
RESULTS: TSH, FT4, PCSK9, non-high-density lipoprotein cholesterol (non-HDL-C), 
LDL-C, and apolipoprotein B (apoB) levels were not different between 64 nonobese 
subjects (BMI<30 kg/m(2)) and 10 obese subjects (BMI≥30 kg/m(2); p>0.20 for 
each). PCSK9 correlated positively with TSH in nonobese subjects (r=0.285, 
p=0.023). In contrast, PCSK9 was not associated positively with TSH in obese 
subjects (r=-0.249, p=0.49). The relationship of PCSK9 with TSH was different 
between nonobese and obese subjects when taking age, sex, FT4, and the presence 
of anti-thyroid antibodies into account (multiple linear regression analysis: 
β=-0.320, p=0.012 for the interaction term between the presence of obesity and 
TSH on PCSK9), and was also modified by BMI as a continuous trait (β=-0.241, 
p=0.062 for the interaction term between BMI and TSH on PCSK9). Non-HDL-C, 
LDL-C, and apoB levels were dependent on PCSK9 in nonobese subjects (p≤0.01 for 
each), but not in obese subjects (p>0.50), Accordingly, BMI interacted 
negatively with PCSK9 on non-HDL-C (p=0.028) and apoB (p=0.071).
CONCLUSIONS: This study suggests that circulating PCSK9 levels correlate with 
thyroid function even in the normal range. This relationship appears to be 
blunted by obesity. Thyroid functional status may influence cholesterol 
metabolism through the PCSK9 pathway.