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Carbimazole Treatment in Smokers vs Nonsmokers With Graves Disease

Jae Il Shin, MD; Jae Seung Lee, MD
JAMA. 2009;301(19):1988-1989. doi:10.1001/jama.2009.556
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To the Editor: The Research Letter by Dr Nyirenda and colleagues1 demonstrated that cigarette smokers compared with nonsmokers showed a much slower reduction in concentrations of thyroid-stimulating hormone (TSH)–receptor antibody, free thyroxine (FT4), and total triiodothyronine (T3) with carbimazole treatment. Smokers required higher doses of carbimazole than nonsmokers. As possible causes for these results, the authors speculated about several factors such as kinetic variability among individuals; the effect of smoking on carbimazole absorption, concentration in the thyroid gland, or metabolism; and the effect of smoking on expression of microsomal enzymes, which could influence the concentration of carbimazole or its metabolites.

Although not extensively studied, the immune functions of smokers and nonsmokers may have differences in the soluble IL-2 receptor system, which is associated with activation of T lymphocytes. In one study,2 cigarette smokers had significantly higher soluble IL-2 receptor levels than nonsmokers (508 vs 420 U/mL; P = .01) and smoking cessation appeared to normalize soluble IL-2 receptor levels.

In another study,3 soluble IL-2 receptor levels were increased in patients with untreated Graves disease; the levels were highly correlated with the markers of Graves disease activity and decreased during carbimazole treatment. Soluble IL-2 receptor levels were highly correlated with T3 levels (P < .001), early uptake of iodine 131 (P = .007), and anti–thyrotropin receptor antibody levels (P = .02).3 Therefore, although not measured in the study by Nyirenda et al, there is a possibility that smoking might result in a higher required dose and blunted response to carbimazole in patients with Graves disease by increasing soluble IL-2 receptor levels, which might affect the levels of TSH-receptor antibody and thyroid hormone.

Further studies are necessary to evaluate the relationships among smoking, carbimazole pharmacokinetics, and soluble IL-2 receptor levels. The effect of race on the levels of soluble IL-2 receptor, TSH-receptor antibody, and thyroid hormone in smokers and nonsmokers should be further assessed, because significantly higher soluble IL-2 receptor levels were reported in white vs black individuals (455 vs 365 U/mL; P < .001).2

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Nyirenda MJ, Taylor PN, Stoddart M, Beckett GJ, Toft AD. Thyroid-stimulating hormone–receptor antibody and thyroid hormone concentrations in smokers vs nonsmokers with Graves disease treated with carbimazole.  JAMA. 2009;301(2):162-164
PubMedCrossRef
Tollerud DJ, Kurman CC, Nelson DL, Brown LM, Maloney EM, Blattner WA. Racial variation in serum-soluble interleukin-2 receptor levels: a population-based study of healthy smokers and nonsmokers.  Clin Immunol Immunopathol. 1994;70(3):274-279
PubMedCrossRef
Weryha G, Gobert B, Leclère J, Béné MC, Faure G, Hartemann P. Dynamic changes in soluble interleukin-2 receptor levels during treatment of Graves' disease: correlation with disease activity.  Horm Res. 1991;35(1):8-12
PubMedCrossRef

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Nyirenda MJ, Taylor PN, Stoddart M, Beckett GJ, Toft AD. Thyroid-stimulating hormone–receptor antibody and thyroid hormone concentrations in smokers vs nonsmokers with Graves disease treated with carbimazole.  JAMA. 2009;301(2):162-164
PubMedCrossRef
Tollerud DJ, Kurman CC, Nelson DL, Brown LM, Maloney EM, Blattner WA. Racial variation in serum-soluble interleukin-2 receptor levels: a population-based study of healthy smokers and nonsmokers.  Clin Immunol Immunopathol. 1994;70(3):274-279
PubMedCrossRef
Weryha G, Gobert B, Leclère J, Béné MC, Faure G, Hartemann P. Dynamic changes in soluble interleukin-2 receptor levels during treatment of Graves' disease: correlation with disease activity.  Horm Res. 1991;35(1):8-12
PubMedCrossRef
May 20, 2009
Moffat J. Nyirenda, MRCP; Geoffrey J. Beckett, PhD, FRCPath; Anthony D. Toft, MD
JAMA. 2009;301(19):1988-1989.
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