Pancreatitis glucocorticoids

Uncommon causes of diabetes (1% to 2% of cases) include endocrine disorders (e.g., acromegaly, Cushing s syndrome), gestational diabetes mellitus (GDM), diseases of the exocrine pancreas (e.g., pancreatitis), and medications (e.g., glucocorticoids, pentamidine, niacin, and a-interferon). 

Davani B, Khan A, Hult M, et al. Type 1 1 lbeta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. J Biol Chem 2000 275(45) 34841-34844. 

When glucocorticoids are used for short periods (< 2 weeks), it is unusual to see serious adverse effects even with moderately large doses. However, insomnia, behavioral changes (primarily hypomania), and acute peptic ulcers are occasionally observed even after only a few days of treatment. Acute pancreatitis is a rare but serious acute adverse effect of high-dose glucocorticoids. 

Pancreatitis and altered pancreatic secretion can occur at any time during long-term glucocorticoid treatment (SED-12, 986 SEDA-14, 339 160). Necrosis of the pancreas during glucocorticoid treatment has been described and can be lethal. Impairment of pancreatic function can predispose to glucocorticoid-induced pancreatitis. Two other cases of glucocorticoid-induced pancreatitis have been reported (161). 

Di Fazano CS, Messica O, Quennesson S, Quennesson ER, Inaoui R, Vergne P, Bonnet C, Bertin P, Treves R. Two new cases of glucocorticoid-induced pancreatitis. Rev Rhum Engl Ed 1999 66(4) 235. 

As indicated earlier, most cases of type 1 diabetes are caused by an autoimmune response that selectively attacks and destroys pancreatic beta cells in susceptible individuals. Therefore, drugs that suppress this autoimmune response may be helpful in limiting beta cell destruction, thereby decreasing the severity of this disease.4,41 Several immunosuppressants have been investigated as a way to potentially minimize beta cell loss from the autoimmune reactions underlying type 1 diabetes some immunosuppressants that have been considered for this situation include cyclosporine, azathioprine, cyclophosphamide, methotrexate, and glucocorticoids.11 The pharmacology of these immunosuppressants is discussed in more detail in Chapter 37. 

In a randomized, multicenter study in 94 patients, mesalazine 4 g/day for 12 weeks in a microgranular formulation was as effective as a standard dose of a glucocorticoid (6-methylpredisolone 40 mg/day) in mild to moderate Crohn s ileitis (Crohn s Disease Activity Index 180-350) (9). The group treated with methylpredisolone had a higher number of adverse events than those given mesalazine. The only adverse effect related to mesalazine was acute pancreatitis, which resolved on withdrawal. 

Ihara, H. and Nakanishi, S. (1990). Selective inhibition of expression of the substance P receptor mRNA in pancreatic acinar AR42J cells by glucocorticoids. J. Biol. Chem. 265, 22441-22445. 

Congestive heart failure Hypertension Deep vein thrombosis Coronary artery disease Stroke Diabetes Insulin resistance Glucocorticoid imbalance Gall bladder disease Hypercholesterolemia Hypertriglyceridemia Gout Pancreatitis Liver disease Osteoarthritis Rheumatoid arthritis Bone fractures Lower back pain Carpal tunnel syndrome Depression Pain... 

Deficiency of hormones (e.g., glucocorticoids, growth hormone) Insulin-producing pancreatic tumors (insulinoma)... 

Methyldopa can cause hemolytic anemia. At least 20% of patients who receive methyldopa for a year develop a positive Coombs test due to autoantibodies directed against the Rh antigen on erythrocytes. This does not necessitate drug discontinuation 1—5% of these patients will develop a hemolytic anemia that mandates prompt drug discontinuation. The Coombs test may remain positive for as long as a year cffter discontinuation of methyldopa, but the hemolytic anemia usually resolves within a matter of weeks. Severe hemolysis may be attenuated by treatment with glucocorticoids. Rarer adverse effects include leukopenia, thrombocytopenia, red cell aplasia, lupus erythematosus—like syndrome, lichenoid and granulomatous skin eruptions, myocarditis, retroperitoneal fibrosis, pancreatitis, diarrhea, and malabsorption. 

Decreases in serum cortisol levels in humans after a single oral dose of zinc sulfate may indicate adrenal cortical damage (Brandao-Neto et al. 1990a). A chronic-duration drinking water study in rats exposed to 70 mg/kg/day revealed hypertrophy and vacuolation of the zona fasciculata cells of the adrenal cortex (Aughey et al. 1977). Glucocorticoids (cortisol, cortisone, corticosterone, deoxycorticosterone) are secreted by cells in the zona fasciculata. It is not known if there is a relationship between the damage to the pancreatic islets and the hypertrophy of the zona fasciculata cells in the adrenal cortex. 

Sadr-Azodi O, Mattsson F, Bexlius TS, Lindblad M, Lagergren J, Ljrmg R. Association of oral glucocorticoid use with an increased risk of acute pancreatitis a population-based nested case-control study. JAMA Intern Med 2013 173(6) 444-9. 

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