SUBKLİNİK HİPOTROİDİLİ HASTALARDA LEVOTİROKSİN TEDAVİSİ ÖNCESİ VE SONRASI SCD40L DÜZEYLERİNİN KARŞILAŞTIRILMASI

Yıl 2014, Cilt: 18 Sayı: 4, 94 - 99, 01.12.2014

Öncesi Ve Sonrasi Scd Ferda Bilgir Oktay Bilgir Mehmet Calan Ozlem Gursoy Calan Arif Yuksel Prof Dr Oktay Bilgir

Öz

Çalışmanın amacı Subklinik Hipotroidide SHO inflamasyon, tromboz ve ateroskleroz işareti olan sCD40L düzeyinin belirlenmesi ve levotiroksin tedavisi ile değişip değişmediğini göstermektir. Subklinik Hipotroidi tanısı alan 32 hasta ile 30 sağlıklı kontrol grubu çalışmaya alındı. SHO’lu hastaların 3 ay levotiroksin tedavisi aldıktan sonra kan örnekleri tekrar alındı. TSH,FT3,FT4 ve sCD40L düzeyleri belirlenerek gruplar arası karşılaştırıldı. sCD40L düzeyleri SHO hasta grubunda kontrol grubuna göre anlamlı ölçüde yüksek bulundu p=0.0001 . sCD40Ldüzeyindeki artış 3 aylık 50µg/gün levotiroksin tedavisi verildikten sonrasında da gözlendi ancak bu sonuç istatistiksel olarak anlamlı değildi p=0.587 . sCD40Lile trombosit düzeyleri arasındaki ilgi Pearson Correlation ile analizi yapıldı ve anlamlı korelasyon yoktu t= -0,07, p=0,955 . Sağlıklı kontrol grubu ile karşılaştırıldığında SHO’lu grupta sCD40L düzeyi yüksek bulundu ve 3 aylık levotiroksin tedavisi sonrasında da devam ediyordu, bu bize hormon replasman tedavisinin hastalık riskini azaltmadığını, yeni tedavi stratejileri geliştirilmesi gerektirdiğini düşündürmektedir

COMPARISON OF SCD40L LEVELS IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM BEFORE AND AFTER LEVOTHYROXINE TREATMENT

Öz

The aim of the study is to determine sCD40L levels which is the sign for inflammation, thrombosis, atherosclerosis in common subclinical hypothyroidism SHO and if there is change in sCD40L levels after levothyroxine treatment. Thirty-two patients diagnosed with subclinical hypothyroidism and 30 healthy control group is enrolled in the study. In patients with SHO, blood samples were re-collected after a 3 months treatment of levothyroxine. TSH, FT3, FT4 and sCD40L levels were determined and levels were compared between groups. sCD40L levels were found significantly high in SHO patient group than control group p=0.0001 . Increase in sCD40L levels are observed after 3 months treatment of 50 µg/day levothyroxine but this result was not statistically significant p=0.587 . The relation between sCD40L levels and platelet count were analysed with Pearson Correlation analysis but no significant correlation could be determined. t= -0,07, p=0,955 . As sCD40L levels are found to be high in SHO patients compared with healthy control group, and continuation of being high after levothyroxine treatment for 3 months makes us think that, the hormone replacemant therapy does not reduce the risk of disease and new treatment strategies should be improved

Anahtar Kelimeler

Subclinical hypothyroidism, sCD40L, levothyroxine

Kaynakça

• ) Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol 1977 ;7: 481–93.
• ) Rosenthal MJ, Hunt WC, Garry PJ, et al. Thyroid failure in the elderly: microsomal antibodies discriminant for therapy. JAMA 1987;258:209–13.
• ) Anand SX, Viles-Gonzalez JF, Badimon JJ, Cavusoglu E, Marmur JD. Membrane- associated CD40L and sCD40L in atherothrombotic disease. Thromb Haemost ;90:377– 84. ) Schonbeck U, Libby P. The CD40/CD154 receptor/ligand dyad. Cell Mol LifeSci 2001; :4–43
• )Chen Y, Chen J, Xiong Y, et al. Internalization of CD40 regulates its signal transduction in vascular endothelial cells. Biochem Biophys Res Commun 2006;345:106 –17.
• )Deregibus MC, Buttiglieri S, Russo S, Bussolati B, Camussi G. CD40-dependent activation of phosphatidylinositol 3-kinase/Akt pathway mediates endothelial cell survival and in vitro angiogenesis. J Biol Chem.2003;278:18008 –14.
• ) Paulie S, Rosen A, Ehlin-Henriksson B, Braesch-Andersen S, Jakobson E, Koho H, Perlmann P. The human B lymphocyte and carcinoma antigen, CDw40, is a phosphoprotein involved in growth signal transduction. J. Immunol 1989;142:590–5.
• ) Ledbetter JA, Shu G, Gallagher M, Clark EA. Augmentation of normal and malignant B cell proliferation by monoclonal antibody to the B cell-specific antigen BP50 (CDW40). J. Immunol ;138:788–94. ) Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S. The CD40 antigen and its ligand. Annu. Rev. Immunol 1994;12:881–922.
• ) Lane P, Traunecker A, Hubele S, Inui S, Lanzavecchia A, Gray D. Activated human T cells Express a ligand for the human B cell-associated antigen CD40 which participates in T cell- dependent activation of B lymphocytes. Eur. J. Immunol 1992;22:2573–8.
• ) Jabara HH, Fu SM, Geha RS, Vercelli D. CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells. J. Exp.Med 1990;172:1861–4.
• ) Callard RE, Smith SH, Herbert J, Morgan G, Padayachee M, Lederman S, Chess L, Kroczek RA, Fanslow WC, Armitage RJ. CD40 ligand (CD40L) expression and B cell function in agammaglobulinemia with normal or elevated levels of IgM (HIM). Comparison of X-linked, autosomal recessive, and non-X-linked forms of the disease, and obligate carriers. J. Immunol ;153:3295–306.
• ) Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC. Mechanism of antigen- driven selection in germinal centres. Nature ;342:929–31. ) Mohan C, Shi Y, Laman JD, Datta SK. Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J. Immunol 1995;154:1470–80.
• ) Im SH, Barchan D, Maiti PK, Fuchs S, Souroujon MC. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4. J. Immunol ;166:6893–8.
• ) Chen CR, Aliesky HA, Guo J, Rapoport B, McLachlan SM. Blockade of costimulation between T cells and antigen-presenting cells: an approach to suppress murine Graves' disease induced using thyrotropin receptor-expressing adenovirus. Thyroid 2006;16:427–34.
• ) Nannizzi-Alaimo L, Alves VL, Phillips DR. Inhibitory effects of glycoprotein IIb/IIIa antagonists and aspirin on the release of soluble CD40 ligand during platelet stimulation. Circulation 2003;107:1123–8.
• ) Antoniades C, Tousoulis D, Vasiliadou C, Stefanadi E, Marinou K, Stefanadis C. Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction. J Am Coll Cardiol 2006;47:1959–66.
• ) Tousoulis D, Antoniades C, Nikolopoulou A, et al. Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes. Eur J Clin Invest 2007;37:623– 8.
• ) Pryshchep O, Ma-Krupa W, Younge BR, Goronzy JJ, Weyand CM. Vessel-specific toll-like receptor profiles in human medium and large arteries. Circulation 2008;118:1276–84.
• ) Erbel C, Sato K, Meyer FB, et al. Functional profile of activated dendritic cells in unstable atherosclerotic plaque. Basic Res Cardiol ;102:123–32. ) Poggi M, Jager J, Paulmyer-Lacroix O, et al. The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes. Diabetologia 2009;52:1152–63.
• ) Schafer A, Wiesmann F, Neubauer S, Eigenthaler M, Bauersachs J, Channon KM. Rapid regulation of platelet activation in vivo by nitric oxide. Circulation 2004;109:1819 –22.
• ) Taddei S, Caraccio N, Airdis A, Dardano A, Versari D, Ghiadoni L, Ferrannini E, Salvetti A, Monzani F. Low-Grade Systemi Inflammation Causes Endothelial Dysfunction in Patients with Hashimoto’s Thyroiditis. J Clin Endocrinol Metab ; 91:5076-82.
• ) Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab 2007;92:1715–23.
• )Marfella R, Ferrariccio F, Rizzo MR, Portoghese M, Barbieri M, Basilio C, Nersita R et al. Innate Immune Activity in Plaque of Patients with Untreated and L-Thyroxine-Treated Subclinical Hypothyroidism.J ;96:1015-20.