Keywords
Adrenal Cortex Hormones; Cytokines; Pancreatitis; Pancreatitis, Acute Necrotizing; Therapeutics
Corticosteroid administration for the treatment of acute pancreatitis is still being debated. In experimental acute pancreatitis, the results of this therapeutic option vary widely; some authors report an improvement of survival in different models of the disease in various animal species such as rats, rabbits, and dogs [1, 2, 3, 4] and others report an increase in the mortality rate after high-dose hydrocortisone treatment in rats with mild and severe disease, and a deteriorated outcome in hydrocortisone pre-treated rats with dietinduced acute pancreatitis [1, 2, 3, 4, 5]. Furthermore, a high-dose, long-term hydrocortisone treatment of 2 weeks was associated with an increased infection or sepsis rate, thereby worsening the outcome of experimental acute pancreatitis [5], and in high-dose, short term hydrocortisone therapy, no benefit regarding survival was shown [6, 7, 8]. However, recently published papers showed promising results with moderate and low dose hydrocortisone treatment over a period varying from 7 to 14 days and these positive effects regard the ameliorated hemodynamic status, the reduced number of organ failures, and the increased incidence of survival [9, 10, 11, 12, 13, 14].
At present, we are familiar with the role of various mediators in the development of systemic inflammatory response syndrome and multiple organ dysfunction syndrome in severe acute pancreatitis. This knowledge includes cytokines, tumor necrosis factor, platelet-activating factor and C-reactive protein, procalcitonin and granulocyte colonystimulating factor, alfa-1-antitrypsin, elastase from polymorphonuclear granulocytes, phospholipase-A2, trypsin, and carboxypeptidase B [15, 16, 17, 18, 19, 20, 21], capable of influencing glucocorticoids. The role of endogenous glucocorticoid metabolism itself and, respectively, its separate components, including total and free cortisol, corticosteroid-binding globulin, and adrenocorticotropic hormone, in the course of acute pancreatitis remains to be elucidated. For this reason, we welcome the paper of Muller et al. [22]; the authors measured how total cortisol, calculated free cortisol, corticosteroid-binding globulin and adrenocorticotropic hormone levels changed in the early course of human acute pancreatitis, and evaluated whether there was any relationship of those changes to the development of pancreatic necrosis. They found that, initially, highly elevated levels of calculated free cortisol and total cortisol, and depressed levels of adrenocorticotropic hormone and corticosteroid-binding globulin were observed. Moreover, daily measurements revealed increasing adrenocorticotropic hormone levels whereas cortisol levels decreased. Although an increase in adrenocorticotropic hormone levels is suggested to increase corresponding cortisol levels, cortisol levels decreased during the development of necrotizing acute pancreatitis. This phenomenon, along with the continuously decreasing corticosteroid binding globulin levels, brings up the hypothesis of a relative adrenal insufficiency which favors acinar cell apoptosis and may trigger the development of necrosis in the initial phase of acute pancreatitis.
According to the study by Muller et al. [22], early short-term therapy with hydrocortisone in low doses to prevent systemic inflammatory response syndrome and the development of necrosis in the early phases of acute pancreatitis may be hypothesized. Thus, studies evaluating dosage, application time, and a time period related to hydrocortisone therapy should be carried out.
References
- Gloor B, Uhl W, Tcholakov O, Roggo A, Muller CA, Worni M, Buchler MW. Hydrocortisone treatment of early SIRS in acute experimental pancreatitis. Dig Dis Sci 2001; 46:2154-61. [PMID 11680590]
- Abe R, Shimosegawa T, Kimura K, Abe T, Kashimura J, Koizumi M, Toyota T. The role of endogenous glucocorticoids in rat experimental models of acute pancreatitis. Gastroenterology 1995; 109:933- 43. [PMID 7544752]
- Osman MO, Jacobsen NO, Kristensen JU, Larsen CG, Jensen SL. Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis. Dig Surg 1999; 16:214-21. [PMID 10436370]
- Imahori SC, Studley JG, Schenk WG Jr. Experimental acute pancreatitis in dogs and effects of steroids. A light and electron microscopic study with reference to pathogenesis. Pathol Res Pract 1984; 178:483-90. [PMID 6462952]
- Manso MA, Rebollo A, Pescador R, de Dios I. Action of CCK on CDE diet-induced acute pancreatitis in rats treated with hydrocortisone. CompBiochemPhysiol C PharmacolToxicolEndocrinol 1995; 111:257-63. [PMID 8521247]
- Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controlled clinical trial of highdose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317:653- 8. [PMID 3306374]
- Sprung CL, Caralis PV, Marcial EH, Pierce M, Gelbard MA, Long WM, Duncan RC, Tendler MD, Karpf M. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med 1984; 311:1137-43 [PMID 6384785]
- The Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 1987; 317:659-65. [PMID 2888017]
- Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 1998; 26:645-50. [PMID 9559600]
- Briegel J, Kellermann W, Forst H, Haller M, Bittl M, Hoffmann GE, et al. Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group. ClinInvestig 1994; 72:782-7. [PMID 7865982]
- Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999; 27:723-32. [PMID 10321661]
- Bohrer H, Schmidt H, Bach A, Bottiger BW, Motsch J. Masking of the symptoms of esophageal and bowel perforation by combination treatment of sepsis with polyvalent immunoglobulins and low-dose hydrocortisone. Hepatogastroenterology 1996; 43:515- 8. [PMID 8799386]
- Meduri GU. New rationale for glucocorticoid treatment in septic shock. J Chemother 1999; 11:541- 50. [PMID 10678798]
- Soni A, Pepper GM, Wyrwinski PM, Ramirez NE, Simon R, Pina T, et al. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. Am J Med 1995; 98:266-71. [PMID 7872343]
- Pezzilli R, Billi P, Miniero R, Fiocchi M, Cappelletti O, Morselli-Labate AM, et al. Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein. Dig Dis Sci 1995; 40:2341-8. [PMID 7587812]
- Uhl W, Buchler M, Malfertheiner P, Martini M, Beger HG. PMN-elastase in comparison with CRP, antiproteases, and LDH as indicators of necrosis in human acute pancreatitis. Pancreas 1991; 6:253-9. [PMID 1713669]
- Buchler M, Malfertheiner P, Schoetensack C, Uhl W, Beger HG. Sensitivity of antiproteases, complement factors and C-reactive protein in detecting pancreatic necrosis. Results of a prospective clinical study. Int J Pancreatol 1986; 1:227-35. [PMID 2445867]
- Muller CA, Uhl W, Printzen G, Gloor B, Bischofberger H, Tcholakov O, Buchler MW. Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis. Gut 2000; 46:233-8. [PMID 10644318]
- MelziD'Eril GV, Merlini G, Finazzi S, Bosoni T, Barakat B, Pezzilli R. Procalcitonin is not a reliablemarker for the assessment of severity in acute pancreatitis without infectious complications. ClinChem 2000; 46:428-30. [PMID 10702536]
- Pezzilli R, Billi P, Plate L, Bongiovanni F, MorselliLabate AM, Miglioli M. Human pancreasspecific protein/procarboxypeptidase B: a useful serum marker of acute pancreatitis. Digestion 1994; 55:73-7. [PMID 7514550]
- Pezzilli R, Morselli-Labate AM, Barbieri AR, Plate L. Clinical usefulness of the serum carboxypeptidase B activation peptide in acute pancreatitis. JOP. J Pancreas (Online) 2000; 1:58-68. [PMID 11854559]
- Muller CA, Vogeser M, Belyaev O, Gloor B, Strobel O, Weyhe D, et al. Role of endogenous glucocorticoid metabolism in human acute pancreatitis. Crit Care Med 2006; Apr 13. [PMID 16484908]