The prevalence of adrenal insufficiency in cirrhosis and the role of salivary cortisol in the diagnosis

Öz

Background and Aims: The objective of this study was to assess the prevalence of adrenal insufficiency according to total and salivary cortisol and to evaluate the discrepancy between these parameters for diagnosis among stable cirrhotic patients. Materials and Methods: A total of 110 consecutive patients with cirrhosis and 30 healthy controls were enrolled into the study. Baseline complete blood count, albumin, bilirubin, prothrombin time, and total and salivary cortisol levels were measured in both patients and controls and free cortisol level was calculated according to Coolens formula. One hour after the administration of 250 μg synacthen, total and salivary cortisol levels were measured and free cortisol was calculated accordingly. Results: The mean age of the patients was 62.7±11.4 years, and there were 54 males (49.1%). Adrenal insufficiency was present in 23 (20.9%) and 17 (15.5%) patients according to total and free cortisol, respectively. At least one of the criteria for adrenal insufficiency for salivary cortisol was present in 24 (21.8%) patients. Patients with baseline salivary cortisol

Anahtar Kelimeler

• Cirrhosis, adrenal insufficiency, salivary cortisol

Sirotik hastalarda adrenal yetmezlik prevalansı ve tanıda tükürük kortizolünün yeri

Öz

Giriş ve Amaç: Stabil sirotik hastalarda, total kortizol ve tükürük kortizolüne göre adrenal yetmezlik prevalansının belirlenmesi ve tanıda bu kriterlerin uyumunun araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya 110 hasta ve 30 sağlıklı kontrol alındı. Hasta ve kontrollerin bazal tam kan sayımı, albümin, bilirubin, protrombin zamanı, total kortizol, tükürük kortizolü, kortizol bağlayacı globülin değerleri ölçüldü. Serbest kortizolleri Coolens formülü ile hesaplandı. Hastaların 250 mg synacten uygulanması sonrası, 1. saatte total ve tükürük kortizolü ölçülüp, serbest kortizol düzeyleri hesaplandı. Bulgular: Hastaların yaş ortalaması 62.1±11.4 yıl olup, 54’ü (%49.1) erkek idi. Ortalama Child skoru 7.2±2.3 olup, 56’sı (%50.9) Child A, 32’si (%29.1) Child B ve 22’si (%20) Child C idi. Total kortizole göre 23 (%20.9), serbest kortizole göre ise 17 hastada (%15.5) adrenal yetmezlik saptandı. Yirmidört hasta (%21.8) tükürük kortizolü için tanı kriterlerinden en az birini sağladı. Bazal tükürük kortizolü < 1.81 ng/ml olup, ACTH sonrası yeterli tükürük kortizol artışı sağlayamayanlar ile tükürük kortizolü 1.saat < 4.96 ng/ml ve delta < 3 ng/ml olanlar gerçek adrenal yetmezlik için daha yüksek olasılıklı olup, hastaların %12.7’sini oluşturmuştur. Tükürük ve total kortizol kriterlerinin uyumu zayıf saptandı (kappa: 0.161). Bazal total kortizol, bazal tükürük kortizolü (r:0.502, p < 0.0001) ve serbest kortizol ile (r:0.579, p < 0.0001) orta derecede pozitif korelasyon gösterdi. Bazal tükrük kortizolü ve serbest kortizol arasında ise güçlü korelasyonu saptandı (r: 0.706, p < 0.0001). Sonuç: Siroz hastalarında, total kortizole göre adrenal yetmezlik, serbest ve tükürük kortizolüne kıyasla daha yüksek saptanmıştır. Tükürük kortizolü serbest kortizol ile güçlü korelasyon göstermesi nedeniyle, sirotik hastalarda adrenal yetmezlik tanısı için uygun bir seçenek olabilir.

Anahtar Kelimeler

• Siroz, adrenal yetmezlik, tükürük kortizolü

Kaynakça

1. Fede G, Spadaro L, Tomaselli T, et al. Assessment of adrenocortical reserve in stable patients with cirrhosis. J Hepatol 2011;54:24350.
2. Tan T, Chang L, Woodward A, et al. Characterizing adrenal function using directly measured plasma free cortisol in stable liver disease. J Hepatol 2010;53:841-8.
3. Marik PE, Gayowsky T, Starzl TE. The hepatoadrenal syndrome: A common yet unrecognized clinical condition. Crit Care Med 2005;33:1254-9.
4. Tsai MH, Peng YS, Chen YC, et al. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology 2006;43:673-81.
5. Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology 2002;36:395-402.
6. Thierry S, Giroux Leprieur E, Lecuyer L, et al. Echocardiographic features, mortaltiy and adrenal function in patients with cirrhosis and septic shock. Acta Anaesthesiol Scand 2008;52:45-51.
7. Fernandez J, Escorsell A, Zabalza M, et al. Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival. Hepatology 2006;44:1288-95.
8. Thevenot T, Borot S, Remy-Martin A, et al. Assessing adrenal function in cirrhotic patients: Is there a reliable test? Gastroenterol Clin Biol 2009;33:584-8.

9. Basic and clinical endocrinology. 7th ed. Greenspan FS, Gardner DG. New York: Lange Medical Books/McGraw-Hill; 2004.
10. Hamrahian AH, Oseini TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Eng J Med 2004;350:1629-38.
11. Gatti R, Antonelli G, Prearo M, et al. Cortisol assays and diagnostic laboratory procedures in human biological fluids. Clin Biochem 2009;42:1205-17.
12. Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: A surrogate marker of the circulating free cortizol. J Clin Endocrinol Metab 2007;92:2965-71.
13. Coolens JL, Van Baelen H, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem 1987;26:197-202.
14. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-71.
15. Gröschl M. Current status of salivary hormone analysis. Clin Chem 2008;54:1759-69.
16. Galbois A, Rudler M, Massard J, et al. Assesment of adrenal function in cirrhotic patients: salivary cortisol should be preferred. J Hepatol 2010;52:839-45.
17. Williams Text Book of Endocrinology. 11th edition. Edited by Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Philadelphia, PA, Sounders; 2008.
18. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008;36:1937-49.
19. Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during high-dose short synacthen test. Eur J Endocrinol 2009;160:9-16.
20. Lewis JG, Bagley CJ, Elder PA, et al. Plasma free cortisol fraction reflects levels of functioning corticosteroid binding globulin. Clin Chim Acta 2005;359:189-94.
21. Vogeser M, Briegel J, Zachoval R. Dialyzable free cortisol after stimulation with Synacten. Clin Biochem 2002;35:539-43.
22. Mc Donald JA, Handelsman DJ, Dilworth P, et al. Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease. J Gastroenterol Hepatol 1993;8:247-53.
23. Thevenot T, Borot S, Remy-Martin A, et al. Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol. Liver Int 2011;31:425-33.
24. Arafah BM. Review: Hypothalamic pituitary adrenal function during critical illness: Limitation of current assessment methods. J Clin Endocrinol Metab 2006;91:3725-45.
25. Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metab Res 2009;41:834-9.
26. Perogamvros I, Owen LJ, Keevil BG, et al. Measurement of salivary cortisol with liquid chromatography-tandem mass spectrometry in patients undergoing dynamic endocrine testing. Clin Endocrinol (Oxf) 2010;72:17-21.
27. Cardosa E, Persi G, Arregger AL, Contreras LN. Assessment of corticoadrenal reserve through salivary steroids. The Endocrinologist 2002;12:38-44.