AKUT KARACİĞER YETMEZLİĞİ OLAN ÇOCUKLARDA TİROİD HORMONLARININ VE HASTALIĞIN SEYRİ İLE İLİŞKİSİNİN DEĞERLENDİRİLMESİ

Öz

Giriş: Çalışmamızda akut karaciğer yetmezliği ile başvuran çocuk hastalarda TSH, serbest T4 ve serbest T3 düzeylerinin hastalık seyrini belirlemedeki etkilerini inceledik.

Gereç ve Yöntemler: Çalışmaya hastanemize 2000-2017 yılları arasında akut karaciğer yetmezliği ile başvuran 108 hasta içerisinden, başvuru sırasında tiroid hormonları bakılmış olan 39 hasta alındı. Bu hastaların geriye dönük olarak klinik ve laboratuvar bulguları değerlendirilerek, başvuru sırasındaki tiroid hormonları ile hastalığın seyri arasındaki ilişki incelendi.

Bulgular: TSH düzeyleri hastaların 29/39’unda (%74,4) normalden düşük, serbest T3 düzeyleri 27/29 hastada (%93,1) normalden düşük saptanmıştır. Serbest T4 düzeyleri ise hastaların %69,4’sında (25/36 hasta) normal düzeylerde bulunmuştur. Hastalar, hastalığın seyrine göre, kendiliğinden düzelen hastalar (Grup 1) ile kaybedilen/nakil olan hastalar (Grup 2) olarak iki gruba ayrılmıştır. Grup 2’deki hastaların başvuru sırasında bakılan INR, total ve direk bilirubin düzeyleri ve PELD skorları grup 1’deki hastalara göre istatistiksel olarak anlamlı şekilde yüksek bulunmuştur (sırasıyla p=0,022, p<0,0001, p=0,003, p=0,004). TSH düzeylerinin ensefalopati evresi ve hemoglobin düzeyi arttıkça azaldığı (sırasıyla p=0,003, r=-0,464 ve p=0,046, r=-0,367), sT4 düzeylerinin ise serum albümin düzeyi arttıkça arttığı (p=0,005, r=0,459) saptanmıştır.

Tartışma: Akut karaciğer yetmezliğinde, serum TSH ve sT3 düzeyleri baskılanmaktadır. Serum TSH düzeyleri ensefalopati evresi ve hemoglobin düzeyi arttıkça azalmakta, sT4 düzeyleri ise serum albümin düzeyi arttıkça artmaktadır. 

Anahtar Kelimeler

• akut karaciğer hastalığı,tiroid hormonları

EVALUATION of THE RELATIONSHIP BETWEEN THYROID FUNCTIONS and DISEASE OUTCOME in CHILDREN WITH ACUTE LIVER FAILURE

Öz

Objective: We investigated if serum TSH, free T4 and free T3 could be prognostic factors in patients with acute liver failure.

Materials and Methods: There were 39 out of 108 children with acute liver failure who applied to our hospital between 2000-2017 and whose thyroid function tests were measured at the time of arrival. We retrospectively collected the clinical and laboratory parameters of these 39 patients, and evaluated the relationship between thyroid hormones and prognosis of the patients.

Results: TSH levels were low in 29/39 (74.4%) patients, while 27/29 (93.1%) patients had low fT3 levels. Free T4 levels were normal in 25/36 (69.4%) patients. Patients were divided into two groups according to disease course: group 1 (n=17) included patients with spontaneous resolution and group 2 (n=22) included patients who either died or underwent liver transplantation. Total and direct bilirubin levels, INR and PELD values were significantly higher in group 2 compared to the levels of group 1 (p=0.022, p<0.0001, p=0.003, p=0.004, respectively). Serum TSH levels were found to decrease with increasing levels of hemoglobin levels and with increasing stages of encephalopathy, and these correlations were statistically significant (p=0.003, r=-0.464 and p=0.046, r=-0.367, respectively). Serum free T4 levels were found to decrease significantly with decreasing levels of serum albumin levels (p=0.005, r=0.459).

Conclusion: Serum TSH and free T3 levels are suppressed in pediatric patients with ALF. Serum TSH levels negatively correlates with increasing stages of encephalopathy, while fT4 levels decrease with decreasing levels of serum albümin.

Anahtar Kelimeler

• acute liver failure,thyroid hormones

Kaynakça

1. 1. Özdemir S. Thyroid and liver. Cerrahpaşa J Med 2005;36:206-12.
2. 2. Sheridan P. Thyroid hormones and the liver. Clin Gastroenterol 1983;12:797-818.
3. 3. Wu Y, You S, Zang H, Liu H, Mao Y, Mao P et al. Usefulness of serum thyroid-stimulation hormone (TSH) as a prognostic indicator for acute-on-chronic liver failure. Ann Hepatol 2015;14:218-24.
4. 4. Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M et al. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation 2003;107:708-13.
5. 5. Friberg L, Werner S, Eggertsen G, Ahnve S. Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina? Arch Intern Med 2002;162:1388-94.
6. 6. Den Brinker M, Joosten KFM, Visser TJ, Hop WCJ, De Rijke YB, Hazelzet JA et al. Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins. J Clin Endocrinol Metab 2005;90:5613-20.
7. 7. Kostopanagiotou G, Kalimeris K, Mourouzis I, Kostopanagiotou K, Arkadopoulos N, Panagopoulos D et al. Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences. Endocrine 2009;36:198-204.8. Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol 2010;205:1-13.
8. 9. Antonelli A, Ferri C, Pampana A, Fallahi P, Nesti C, Pasquini M et al. Thyroid disorders in chronic hepatitis C. Am J Med 2004;117:10-3.

9. 10. Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut 1983;24:631-6.
10. 11. Oren R, Sikuler E, Wong F, Blendis LM, Halpern Z. The effects of hypothyroidism on liver status of cirrhotic patients. J Clin Gastroenterol 2000;31:162-3.
11. 12. Oren R, Brill S, Dotan I, Halpern Z. Liver function in cirrhotic patients in the euthyroid versus the hypothyroid state. J Clin Gastroenterol 1998;27:339-41.
12. 13. Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006;148:652-8.
13. 14. O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342:273-5.
14. 15. Kapelari K, Kirchlechner C, Högler W, Schweitzer K, Virgolini I, Moncayo R. Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study. BMC Endocr Disord 2008;8:15.
15. 16. Ray DC, Macduff A, Drummond GB, Wilkinson E, Adams B, BeckettGJ. Endocrine measurements in survivors and non-survivors from critical illness. Intensive Care Medicine 2002;28:1301-8.
16. 17. Spencer C, Eigen A, Shen D, Duda M, Qualls S, Weiss S, Nicoloff J. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clinical Chemistry 1987;33:1391-6.
17. 18. Anastasiou O, Sydor S, Sowa JP, Manka P, Katsounas A, Syn WK et al. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure. PLoS One 2015;10:e0132189.
18. 19. Attwood EC, Atkin GE. The T4:TBG ratio: a re-evaluation with particular reference to low and high serum TBG levels. Ann Clin Biochem 1982;19:101-3.
19. 20. Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,5,30-triiodothyronine in humans by multicompartmental analysis. American Journal of Physiology 1990;258:715-26.
20. 21. Ataoğlu HE, Ahbab S, Serez MK, Yamak M, Kayaş D, Canbaz ET et al. Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome. Eur J Intern Med 2018;6205:30290-5.
21. 22. Taş A, Köklü S, Beyazit Y, Kurt M, Sayilir A, Yeşil Y, et al. Thyroid hormone levels predict mortality in intensive care patients with cirrhosis. Am J Med Sci 2012;344:175 9.
22. 23. Wang L, Yu W, Cao W, Lu W. The abnormality of thyroid hormones in patients with type A hepatic encephalopathy. Oncotarget 2017;8:67821-8.
23. 24. Fliers E, Guldenaar SE, Wiersinga WM, Swaab DF. Decreased hypothalamic thyrotropin-releasing hormone gene expression in patients with nonthyroidal illness. J Clin Endocrinol Metab1997;82:4032-6.
24. 25. Fliers E, Alkemade A, Wiersinga WM, Swaab DF. Hypothalamic thyroid hormone feedback in health and disease. Prog Brain Res 2006;153:189-207.
25. 26. Nomura R, Miyai K, Kuge R, Okura T, Goto M, Hasegawa Y. Free T3 to free T4 ratio less than 2.0 suggests low T3 syndrome rather than central hypothyroidism from the age of two to eighteen years. Endocr J 2017;64:213-9.
26. 27. Malik R, Mellor N, Selden C, Hodgson H. Triiodothyronine enhances the regenerative capacity of the liver following partial hepatectomy. Hepatology 2003;37:79-86.
27. 28. Malik R, Saich R, Rahman T, Hodgson H. During thioacetamide-induced acute liver failure, the proliferative response of hepatocytes to thyroid hormone is maintained, indicating a potential therapeutic approach to toxin-induced liver disease. Dig Dis Sci 2006;51:2235-41.
28. 29. Fernández V, Castillo I, Tapia G, Romanque P, Uribe-Echevarría S, Uribe M, et al. Thyroid hormone preconditioning: protection against ischemia-reperfusion liver injury in the rat. Hepatology 2007;45:170-7.