Acute TSH stimulation in vivo does not alter serum PCSK9 levels

BACKGROUND: It is now recognized that TSH can act on targets other than the thyroid, including the liver. Elevated serum TSH levels in euthyroid subjects were recently reported to correlate with high values of serum proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein, expressed and secreted by hepatocytes, promotes higher LDL-cholesterol levels. We tested whether an acute increase of TSH levels following administration of TSH in vivo would raise PCSK9 levels in patients who had previously undergone total thyroidectomy and radioablation for thyroid cancer. FINDINGS: TSH levels rose from 0.64 ± 1.02 mU/L on day 1 to 98.66 ± 4.83 mU/L on day 3, following injections of recombinant human TSH (on days 1 and 2). PCSK9 levels were 330 ± 99 ng/ml on day 1, and did not change on days 3 or 5 in response to TSH stimulation. CONCLUSIONS: Although a positive correlation between TSH and PCSK9 in euthyroid subjects has raised the possibility that TSH might act on the liver to raise PCSK9 values, our data show that PCSK9 levels are not affected by acute elevations of TSH levels. Whether chronic elevations of TSH are needed to upregulate PCSK9 remains to be determined.