Filiz ARAZ, Birol ÖZER, Barış SOYDAŞ, Ender SERİN

Sirotik hastalarda adrenal yetmezlik prevalansı ve tanda tükürük kortizolünün yeri

Giriş ve Amaç: Stabil sirotik hastalarda, total kortizol ve tükürük kor- tizolüne göre adrenal yetmezlik prevalansının belirlenmesi ve tanıda bu kriterlerin uyumunun araştırılması amaçlanmıştır. Gereç ve Yön- tem: Çalışmaya 110 hasta ve 30 sa¤lıklı kontrol alındı. Hasta ve kon- trollerin bazal tam kan sayımı, albümin, bilirubin, protrombin zamanı, total kortizol, tükürük kortizolü, kortizol ba¤layacı globülin de¤erleri ölçüldü. Serbest kortizolleri Coolens formülü ile hesaplandı. Hastaların 250 mg synacten uygulanması sonrası, 1.saatte total ve tükürük kor- tizolü ölçülüp, serbest kortizol düzeyleri hesaplandı. Bulgular: Hasta- ların yaş ortalaması 62.1±11.4 yıl olup, 54ü (%49.1) erkek idi. Ortala- ma Child skoru 7.2±2.3 olup, 56sı (%50.9) Child A, 32si (%29.1) Child B ve 22si (%20) Child C idi. Total kortizole göre 23 (%20.9), ser- best kortizole göre ise 17 hastada (%15.5) adrenal yetmezlik saptan- dı. Yirmidört hasta (%21.8) tükürük kortizolü için tanı kriterlerinden en az birini sa¤ladı. Bazal tükürük kortizolü

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

Background and Aims: The objective of this study was to assess the prevalence of adrenal insufficiency according to total and salivary cor- tisol and to evaluate the discrepancy between these parameters for di- agnosis 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 cal- culated according to Coolens formula. One hour after the administra- tion of 250 μg synacthen, total and salivary cortisol levels were measu- red 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 cor- tisol <1.81 ng/ml and without satisfactory cortisol increase following ACTH test, and all patients with salivary cortisol level measured as <4.96 at 1 hour with delta of <3 ng/ml, regardless of baseline value, were accepted as having adrenal insufficiency with the highest proba- bility; these constituted 12.7% of all patients. Baseline total cortisol showed a low correlation with salivary and free cortisol (r: 0.502 and r: 0.579, respectively). In contrast, the correlation between salivary and free cortisol was relatively higher (r: 0.706, p<0.0001). Conclusi- ons: Adrenal insufficiency was diagnosed more commonly according to total cortisol when compared to salivary and free cortisol. Regar- ding the higher correlation of free cortisol with salivary cortisol relati- ve to total cortisol, salivary cortisol could be a suitable alternative for the diagnosis of adrenal insufficiency in patients with cirrhosis.

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1.Fede G, Spadaro L, Tomaselli T, et al. Assessment of adrenocorti- cal reserve in stable patients with cirrhosis. J Hepatol 2011;54:243- 50.
2.Tan T, Chang L, Woodward A, et al. Characterizing adrenal func- tion using directly measured plasma free cortisol in stable liver di- sease. 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 fe- atures, 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 func- tion in cirrhotic patients: Is there a reliable test? Gastroenterol Clin Biol 2009;33:584-8.
9.Basic and clinical endocrinology. 7 th ed. Greenspan FS, Gardner DG. New York: Lange Medical Books/McGraw-Hill; 2004.
10.Hamrahian AH, Oseini TS, Arafah BM. Measurements of serum fre- e 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 diagnos- tic laboratory procedures in human biological fluids. Clin Biochem 2009;42:1205-17.
12.Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of sa- livary 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.Coo- lens 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 func- tion in cirrhotic patients: salivary cortisol should be preferred. J He- patol 2010;52:839-45.
17.Williams Text Book of Endocrinology. 11th edition. Edited by Kro- nenberg 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 criti- cally 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 secon- dary 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 sti- mulation with Synacten. Clin Biochem 2002;35:539-43.
22.Mc Donald JA, Handelsman DJ, Dilworth P, et al. Hypothalamic-pi- tuitary 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 du- ring 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 secon- dary 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 cor- ticoadrenal reserve through salivary steroids. The Endocrinologist 2002;12:38-44.