HASHİMOTO TİROİDİTLİ HASTALARDA ATEROSKLEROZ İLE İLİŞKİLİ PARAMETRELERİN DEĞERLENDİRİLMESİ

Abstract

Amaç Hashimoto tiroiditi otoimmün tiroid hastalığıdır. Aterosklerozda arterlerin subintima tabakasında lipidler, karbonhidratlar, fibröz doku, kalsiyum gibi maddelerin lokal birikimlerinin oluşturduğu patolojik bir durum söz konusudur. Vasküler endotelyal büyüme faktör (VEGF) özellikle hipoksi varlığında seçici olarak endotel hücrelerinde mitojenik etki ile damar gelişimini uyararak yeni damar oluşumunda yaşamsal rol oynar. Biz bu çalışmamızda ötiroid hashimoto hastalarında serum VEGF düzeyi ile akım aracılı dilatasyon (flow-mediated dilation, FMD) ve karotis intima media kalınlığı (KİMK) ölçümü yaparak, otoimmünitenin tiroid hastalarında ateroskleroz ile ilişkisini ortaya koymayı amaçladık. Gereç ve Yöntem Gaziantep Üniversitesi Tıp Fakültesi Dahiliye Kliniği’nde Hashimoto tiroiditi tanısı almış 40 hasta ile yaş ve cinsiyet uyumlu 40 sağlıklı gönüllü çalışmaya dahil edildi. Serum örneklerinde VEGF düzeyleri ELISA yöntemiyle ölçüldü. Hasta ve kontrol grubunda ultrason eşliğinde KİMK ve FMD değerlendirilerek mevcut sonuçlarla ilişkili olup olmadığı tespit edildi. Bulgular Hasta ve kontrol grubunun demografik özellikleri benzerdi. Hasta ve kontrol grupları arasında FMD ve KIMK ölçümleri karşılaştırıldığında istatiksel olarak anlamlı fark saptandı (p=0,001; p=0,033). VEGF düzeyinin de hasta grubunda kontrol grubuna göre anlamlı olarak yüksek olduğu tespit edildi (p=0,024). Sonuç Tüm bu sonuçlar tiroid hormon eksikliği olmadan da otoimmüniteye sekonder ateroskleroz gelişebileceğini ve hashimoto hastalarının erken dönem takiplerinde noninvaziv uygulanabilen FMD, KİMK ölçümlerinin ve VEGF düzeylerinin prediktif değerinin olabileceğini göstermektedir.

Keywords

• Hashimoto tiroiditi
• Ateroskleroz
• VEGF
• KİMT
• FMD

THE EVALUATION OF ATHEROSCLEROSIS RELATED PARAMETERS IN PATIENTS WITH HASHIMOTO’S THYROIDITIS

Abstract

Objective Hashimoto thyroiditis is an autoimmune thyroid disease. Atherosclerosis is a pathological condition characterized by local accumulation of substances such as lipids, carbohydrates, fibrous tissue and calcium in the subintima layer of arteries. In this study, we aimed to reveal the relationship between autoimmunity and atherosclerosis by measuring serum VEGF levels, flow-mediated dilation (FMD) and carotid intima-media thicknes (CIMT) in euthyroid patients with Hashimoto thyroiditis. Materials and Methods Forty patients diagnosed with Hashimoto thyroiditis in the Internal Medicine Clinic of Gaziantep University Medical Faculty and 40 healthy volunteers matched for age and gender were included in the study. VEGF levels were measured by ELISA method in serum samples. CIMT and FMD were evaluated with ultrasound guidance in the patient and control groups and it was determined whether there was a association with the present results. Results The demographic characteristics of the patient and control groups were similar. There was a significant difference between the patients and healthy control group in terms of FMD and CIMC measurements (p = 0.001; p = 0.033). It was also found that VEGF levels of patients were higher than those in the control group (p = 0.024). Conclusion All these results show autoimmunity may lead atherosclerosis even without thyroid hormone deficiency and also noninvasive FMD, CIMT measurements and VEGF levels may have predictive value in the early follow-up of Hashimoto patients.

Keywords

• Atherosclerosis
• VEGF
• CIMT
• FMD
• Hashimoto

References

1. 1. Ahmed R, Al-Shaikh S, Akhtar M. Hashimoto thyroiditis: a century later. Adv Anat Pathol 2012;19(3);181-186.
2. 2. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2455-2646.
3. 3. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997;349(9063):1436-42.
4. 4. Kumral E. Aterosklerozun Epidemiyolojisi ve Genel Özellikleri: Kumral E. Ateroskleroz ve Serebrovasküler Hastalıklar (1. Baskı) İstanbul, Tayf Matbacılık, 2003; 3-9.
5. 5. Erişim: www.tmc.edu/thi/cad.html Erişim Tarihi: 1/09/2005.
6. 6. Kasper DL, Hauser SL, LongoDL, Jameson JL. Çeviri editoru: Sağlıker Y. Harrison İç Hastalıkları Prensipleri (15. Baskı) İstanbul, Nobel Matbaacılık, 2004; 2060-75.
7. 7. Wang Y, Nakayama M, Pitulescu ME, Schmidt TS. Ephrin-B2 Controls VEG İinduced Angiogenesis and Lymphangiogenesis. Nature 2010; 465: 483-486.
8. 8. O'Leary DH, Polak JF. Intima-Media Thickness: a tool for atherosclerosis imaging and event prediction. Am J Cardiol 2002; 90: 18L-21L

9. 9. Kingwell BA. Wall changes induced by blood pressure and antihypertensive drugs in large arteries: Touboul PJ, Hennerici M. Intima- Media Thickness, Drugs and Stroke .(1. Baskı) 2002; 19-24.
10. 10. Weissberg P. Mechanisms modifying atherosclerotic disease from lipids to vascular biology. Atherosclerosis 1999;147(1): 3-10.
11. 11. Yoshida T, Kawano H, Miyamoto S, Motoyama T, Fukushima H, Hirai N, Ogawa H. Prognostic value of flow-mediated dilation of the brachial artery in patients with cardiovascular disease. Internal medicine 2006; 45: 575-9.
12. 12. Neunteufl T, Heher S, Katzenschlager R. Late prognosticvalue of FMD in the brachial artery of patients with chest pain. Am J Cardiol 2000; 86: 207-210.
13. 13. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. New England Journal of Medicine 1987, 316 (22): 1371-1375.
14. 14. Reinehr T, Kiess W, Sousa G, Stoffel-Wagner B, Wunsch R. Intima media thickness in childhood obesity: Relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism. Clinical and Experimental 2006;55:113- 118.
15. 15. Frostegård J. Atherosclerosis in patients with autoimmune disorders. Arterioscler Thromb Vasc Biol 2005; 25(9):1776-85.
16. 16. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L ve ark. Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis. The Journal of Clinical Endocrinology & Metabolism 2006; 91(12):5076-5082.
17. 17. Allan PL, Mowbray PI, Lee AJ. Relationship between carotid intima- media thickness and symptomatic and asymptomatic peripheral arterial disease. Edinburgh Artery Study. Stroke 1997; 28:348- 353
18. 18. Nagasaki T, Inaba M, Henmi Y, Kumeda Y, Ueda M, Tahara H ve ark. Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function. Clin Endocrinol (Oxf). 2003; 59:607-12.
19. 19. Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A ve ark. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo-controlled study. The Journal of Clinical Endocrinology & Metabolism 2004; 89(5 ): 2099-2106.
20. 20. Topaloglu, Oya, et al. Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status?. Endocrine 2013; 44(1): 145-151.
21. 21. Hofbauer LC, Kluger S, Kuhne CA, Dunstan CR, Burchert A, Schoppet M ve ark. Detection and characterization of RANK ligand and osteoprotegerin in the thyroid gland. J Cell Biochem 2002; 86: 642-50.
22. 22. Armstrong AW, Voyles SV, Armstrong EJ, Fuller EN, Rutledge JC. Angiogenesis and oxidative stress: common mechanisms linking psoriasis with atherosclerosis. J Dermatol Sci 2011; 63: 1–9
23. 23. Bhushan M, McLaughlin B, Weiss JB, Griffiths CE. Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis. Br J Dermatol 1999; 141: 1054–1060.
24. 24. Mohammad NS, Elsayed N, Bassiouny R. Increased production of vascular endothelial growth factor in the lesions of psoriasis– a new target for future therapy. J Med Res Inst 2008; 29: 81–86
25. 25. Inoue M, Itoh H, Ueda M, Naruko T, Kojima A, Komatsu R ve ark. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 1998; 98(20):2108-16.
26. 26. Mohammad NS, Elsayed N, Bassıouny R. Increased production of vascular endothelial growth factor in the lesions of psoriasis– a new target for future therapy. Journal Of Medıcal Research Instıtute 2008; 29.1: 81-86.
27. 27. Neunteufl T, Heher S, Katzenschlager R, Kostner K, Maurer G, Weidinger F. Late prognostic value of FMD in the brachial artery of patients with chest pain Am J Cardiol 2000;86:207-210
28. 28. Xiang GD, He YS, Zhao LS, Hou J, Yue L, Xiang HJ. Impairment of endothelium-dependent arterial dilation in Hashimoto's thyroiditis patients with euthyroidism. Clin Endocrinol (Oxf) 2006;64(6):698-702.