CHICAGO — Injection of recombinant human thyroid-stimulating hormone causes a marked and persistent improvement in brachial artery endothelial flow-mediated dilation, without affecting heart rate, blood pressure, or echocardiographic parameters, a small study has shown.
The clinical implication of this finding is that the well-established increased cardiovascular risk associated with hypothyroidism can't be explained by the elevated thyroid-stimulating hormone (TSH) levels accompanying this form of thyroid dysfunction. Indeed, TSH is, if anything, antiatherogenic, Dr. Raffaele Napoli reported at the annual meeting of the American Thyroid Association.
He studied 34 patients with a history of total thyroidectomy for well-differentiated thyroid cancer who received injections of recombinant human thyroid-stimulating hormone on 2 consecutive days, followed by ultrasound assessment of brachial artery flow-mediated dilation (FMD) at 6, 24, 30, and 48 hours and again 5 days after the first injection. In addition, subjects underwent echocardiographic exams at baseline and at 24 hours, had Holter monitoring, and gave blood samples at baseline and at days 2 and 5.
FMD rose by nearly 60% from a baseline of 10.2% to 16.1% at 24 hours and remained elevated at 14.9% all the way out to day 5. The increase in FMD, seen in 33 of the 34 subjects, correlated closely with serum TSH level, which climbed from 0.07 mIU\L at baseline to 147 mIU/L on day 2 and was still high at 15 mIU/L on day 5. Free T3 and free T4 levels were normal at baseline and remained unchanged during follow-up, said Dr. Napoli of the University of Naples (Italy).
Echocardiography and Holter monitoring demonstrated that the rise in circulating TSH did not affect heart rate, blood pressure, left ventricular ejection fraction or diastolic diameter, or diastolic function, he reported.
In terms of atherogenic biomarkers, homocysteine levels dropped significantly from 14 micromol/L at baseline to 12.5 at 48 hours and 10.9 micromol/L at day 5. The C-reactive protein level also declined, but this trend did not reach statistical significance. Levels of the inflammatory biomarkers tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 remained unchanged from baseline.
Audience members asked why hypothyroidism increases cardiovascular risk, given the salutary effects a high TSH level apparently has on flow-mediated dilation. The endocrinologist replied that the multiple negative effects of the low free T4 level that also defines the hypothyroid state trump the high TSH.
“Thyroid hormone is a very powerful hormone, so when you get a decrease in thyroid hormone level, that predominates,” Dr. Napoli explained.
One audience member, noting that homocysteine levels are related to folic acid metabolism, said it is not plausible that homocysteine would drop so quickly—within 2 days—in response to administration of recombinant human TSH. Dr. Napoli said he, too, was dubious about that particular finding.
Increased CV risk associated with hypothyroidism can't be explained by elevated TSH levels. DR. NAPOLI