Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma.
OBJECTIVE
We evaluated endothelial-dependent vasodilation after administration of recombinant human TSH (rhTSH) in patients monitored for differentiated thyroid carcinoma. The role of inflammation and oxidative stress was also assessed.


METHODS
Twenty-four patients (21 women, mean age 40.5 +/- 9.2 yr) received rhTSH (0.9 mg daily) on 2 consecutive days. At baseline and the day after the second rhTSH injection, endothelium-dependent vasodilation as flow-mediated dilation (FMD, induced by 5 min of forearm ischemia) and endothelium-independent vasodilation (glyceril trinitrate 25 microg, sublingual) were evaluated by high-resolution ultrasound in the brachial artery. At each experimental time, blood was drawn for the evaluation of thyroglobulin, TSH, free T(3), free T(4), as well as IL-6, C reactive protein, TNFalpha, lipoperoxides, and ferric reducing antioxidant power levels as markers of inflammation and oxidative stress.


RESULTS
At baseline, patients' serum TSH values were below the normal range [0.12 mIU/liter (range 0.01-0.30)] in the face of normal free T(4) and free T(3) levels; FMD (8.9 +/- 3.4 vs. 9.2 +/- 3.1%, respectively) and response to glyceril trinitrate (11.0 +/- 4.3 vs. 10.8 +/- 4.7%, respectively) were similar in patients and controls. All the patients had serum thyroglobulin value less than 1 ng/ml, suggesting the absence of cancer recurrences. Besides the expected elevation of serum TSH, rhTSH induced a significant impairment of FMD (7.4 +/- 3.0 vs. 8.9 +/- 3.4%; P < 0.01) along with a significant elevation of blood IL-6 (P = 0.01), TNFalpha (P < 0.001), and lipoperoxide levels (P = 0.01), as well as a reduction of ferric reducing antioxidant power (P = 0.01).


CONCLUSIONS
rhTSH administration acutely impaired endothelium-dependent vasodilation, possibly through the induction of low-grade inflammation and reduced nitric oxide availability by oxidative stress.
Dardano
Angela
A
Department of Internal Medicine, University of Pisa, via Roma 67, 56126 Pisa, Italy.
Ghiadoni
Lorenzo
L
Plantinga
Yvonne
Y
Caraccio
Nadia
N
Bemi
Alessia
A
Duranti
Emiliano
E
Taddei
Stefano
S
Ferrannini
Ele
E
Salvetti
Antonio
A
Monzani
Fabio
F
D000328:Adult; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D011994:Recombinant Proteins; D013972:Thyrotropin