Assessment of the utility of the high-dose dexamethasone suppression test in confirming the diagnosis of Cushing disease.

OBJECTIVE: To determine the utility of high-dose dexamethasone suppression (HDDS) tests to confirm the diagnosis of Cushing disease (CD). METHODS: In this retrospective study, we reviewed medical records of patients who underwent either the overnight 8-mg HDDS test or the 2-day 2-mg HDDS test every 6 hours. The percentage suppression of morning serum cortisol and the percentage suppression of 24-hour urine free cortisol (UFC) were calculated. RESULTS: Of 141 patients with proven CD who underwent HDDS tests, 77 (55%) underwent the overnight 8-mg HDDS test and 64 (45%) underwent the 2-day 2-mg HDDS test every 6 hours. With the overnight 8-mg HDDS test, 73 of 77 patients (95%) had greater than 50% suppression and 48 of 77 patients (62%) had greater than 80% suppression of the morning serum cortisol in comparison with the baseline value. With the 2-day 2-mg HDDS test, only 41 of 64 patients (64%) had greater than 90% suppression of 24-hour UFC. CONCLUSION: We conclude that the overnight 8-mg HDDS test accurately confirmed the diagnosis of CD with a high sensitivity of 95% with use of a criterion of greater than 50% suppression; in contrast, the sensitivity was only 62% with use of a more precise cutoff of greater than 80% suppression. The 2-day 2-mg HDDS test with a criterion of greater than 90% suppression of 24-hour UFC had a sensitivity of 64%. These results confirm the limited precision of the HDDS tests.

Long-term kidney transplant outcome in obese patients in a predominantly African American population.

The impact of obesity on long-term kidney transplant outcome has largely been studied in non-African American patients. This study seeks to determine differences in outcome between obese and non-obese patients after kidney transplantation, in a predominantly African American population. We reviewed 642 adult renal transplant recipients who received their transplants at SUNY Downstate Medical Center between 1998 and 2007. Sixty-six percent of the patients studied were African American. The patients were divided into five groups according to their BMI status: underweight <20, normal 20-24.9, overweight 25-29.9, obese 30-34.9, and morbidly obese ≥35. There were no differences in race, gender, cytomegalovirus infection, type of transplant, panel-reactive antibody, retransplant status, flow cytometry cross-match results, mycophenolate mofetil therapy, and total HLA mismatch status. The mean discharge serum creatinine in the morbidly obese group was significantly higher than in other groups (p < 0.001). The difference in creatinine level disappeared at six wk and six months (p > 0.5), respectively. Acute rejection rates, delayed graft function, graft survival, and patient survival were not different between the groups. The findings from this large single-center study suggest that obese and morbidly obese patients had similar outcomes compared to other weight groups. Obese and morbidly obese African American patients should not be excluded from kidney transplantation on the basis of weight alone.

New-onset diabetes after hemodialysis initiation: impact on survival.

BACKGROUND: The incidence of new-onset diabetes after initiation of hemodialysis (NODAD) and its impact on survival is not known. METHODS: We used data from the United States Renal Data System (USRDS) from January 2000 to December 2001, with at least 3 years of follow-up for this study. Patients aged 18-80 years were included. NODAD was defined as two Medicare institutional claims for diabetes in patients with no history of diabetes prior to starting hemodialysis (HD). Incidence (per 1,000 patient-years), prevalence (%) and hazard ratios for mortality in patients with NODAD were calculated. RESULTS: There were 59,340 incident patients with no history of diabetes prior to starting HD, of which 3,853 met criteria for NODAD. The overall incidence and prevalence of NODAD were 20 per 1,000 patient-years and 7.6%, respectively. In a cohort of 444 patients without diabetes and documented glycosylated hemoglobin A1c, <6% prior to starting HD (from January 2005 and March 2006), at a mean follow-up of 4.7 +/- 2.6 months, 6.8% developed NODAD defined by two Medicare claims for diabetes after initiation of HD. NODAD was associated with a significantly increased risk of death as compared to non-diabetes patients (hazard ratio 1.20, 95% confidence interval 1.14-1.25). CONCLUSION: The USRDS showed a high incidence of NODAD, associated with significantly higher mortality compared to those who did not develop NODAD. The mechanism of NODAD needs to be explored further in experimental and clinical studies.

Posttransplant diabetes and hypertension: pathophysiologic insights and therapeutic rationale.

New-onset diabetes after transplantation and hypertension are very common after renal transplantation and are associated with adverse graft and cardiovascular outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of these important disorders. This review outlines the pathogenesis, diagnostic workup, and therapeutic rationale for diabetes and hypertension after transplantation.

Challenges in the diagnosis and management of new-onset diabetes after transplantation.

With the availability of newer and more potent immunosuppressive agents, post-transplant survival has markedly improved. However, these agents, together with the rising age of transplant recipients, have been associated with a rise in the incidence of new-onset diabetes after transplantation (NODAT). Besides the traditional risk factors for diabetes mellitus, such as age, obesity, hypertension, and family history of diabetes, additional risk factors for NODAT are identified. These include immunosuppressive therapy, hepatitis C infection, acute rejection, and deceased donor kidney transplant. In this article, we discuss the epidemiology, risk factors, pathophysiology, clinical course, and therapeutic and diagnostic challenges of this emerging disease.

Challenges in the diagnosis and management of renal artery stenosis.

Renal artery stenosis (RAS) is a common cause of secondary hypertension, with the activation of the renin-angiotensin-aldosterone system being the pathophysiologic hallmark of the disease. Renovascular hypertension, ischemic nephropathy, proteinuria, and flash pulmonary edema are the main clinical syndromes associated with RAS. The prevalence of RAS is on the rise, owing to an increasing prevalence of diabetes and atherosclerotic disease among our aging population. This rise in RAS prevalence poses major challenges for clinicians making diagnostic and treatment decisions. Although renal angioplasty is of proven benefit in fibromuscular dysplasia, randomized trials in atherosclerotic RAS have not shown any advantage for revascularization over medical therapy in terms of blood pressure control or renal function preservation. Angioplasty and surgical interventions should be reserved for patients with preserved kidney size and hemodynamically significant stenosis.

Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes.

Patients with hepatitis C virus (HCV) infection have a greater risk of developing type 2 diabetes mellitus. However, the mechanism of this association is unclear. In this study, we examined the potential defects in upstream insulin signaling pathways in liver specimens obtained from nonobese/nondiabetic subjects with HCV infection. Fasting liver biopsy specimens were obtained from 42 HCV-infected subjects and 10 non-HCV-infected subjects matched for age and body mass index. Liver tissues were exposed to insulin and examined for the contents and phosphorylation/activation status of the upstream insulin signaling molecules by immunoprecipitation and Western blot analysis. HCV infection resulted in a trend toward a 2-fold to 3-fold increase in insulin receptor (IR) and insulin receptor substrate (IRS)-1 contents when compared with non-HCV. In contrast, insulin-stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected subjects compared with non-HCV-infected subjects (P <.05). The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). This was accompanied by a marked reduction in insulin-stimulated Akt phosphorylation without any alterations in mitogen-activated protein kinase (MAPK) phosphorylation. Cellular contents of the hepatic p85 subunit of PI3-kinase were comparable between HCV-infected and non-HCV-infected subjects. In conclusion, we found that (1). HCV infection leads to a postreceptor defect in IRS-1 association with the IR and (2). insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to insulin resistance, which leads to the development of type 2 diabetes mellitus in patients with HCV infection.