Iron metabolism in patients with Graves' hyperthyroidism.

OBJECTIVES: Graves' hyperthyroidism (GH) interferes with iron metabolism and elevates ferritin. The precise mechanisms remain unclear. The influence of thyroid hormones on the synthesis/regulation of hepcidin, an important regulator of iron metabolism, remains uncharacterized. DESIGN: Prospective observational study. PATIENTS: We included patients (n = 31) with new-onset and untreated GH. MEASUREMENTS: Laboratory parameters indicative of iron metabolism (ferritin, transferrin, hepcidin), inflammatory markers/cytokines and smoking status were assessed at the diagnosis of GH (T0) and at euthyroidism (T1) in the same patients using multivariable analyses. Hepcidin was measured by mass spectrometry (hepcidinMS ) and ELISA (hepcidinEL ). The impact of T3 on hepatic hepcidin expression was studied in a cell culture model using HepG2 cells. RESULTS: Median ferritin levels were significantly lower and transferrin significantly higher at T1 than at T0. HepcidinMS levels were lower in males and females at T1 (statistically significant in males only). No statistically significant difference in hepcidinEL was detected between T0 and T1. Plasma levels of inflammatory markers (high-sensitive CRP, procalcitonin) and cytokines (interleukin 6, interleukin 1ß, tumour necrosis factor α) were not different between T0 and T1. Smokers tended to have lower fT3 and fT4 at T0 than nonsmoking GH patients. T3 significantly induced hepcidin mRNA expression in HepG2 cells. CONCLUSIONS: Iron metabolism in patients with GH undergoes dynamic changes in patients with GH that resemble an acute-phase reaction. Inflammatory parameters and cytokines were unaffected by thyroid status. Gender and smoking status had an impact on ferritin, hepcidin and thyroid hormones.

Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI.

OBJECTIVES: Studies evaluating the correlation between the widely used Simple Endoscopic Score for Crohn's disease (SES-CD) and noninvasive markers are scarce. The aim of this study was to evaluate the correlation between the SES-CD and fecal calprotectin, C-reactive protein (CRP), blood leukocytes, and the Crohn's disease activity index (CDAI). METHODS: Crohn's disease patients undergoing complete ileocolonoscopy were prospectively enrolled and scored independently according to the SES-CD and the CDAI. SES-CD was defined as follows: inactive 0-3; mild 4-10; moderate 11-19; and high > or =20. RESULTS: Values in CD patients (n=140 ileocolonoscopies) compared with controls (n=43) are as follows: calprotectin, 334+/-322 vs. 18+/-5 microg/g; CRP, 26+/-29 vs. 3+/-2 mg/l; and blood leukocytes, 9.1+/-3.4 vs. 5.4+/-1.9 g/l (all P<0.001). The SES-CD correlated closest with calprotectin (Spearman's rank correlation coefficient r=0.75), followed by CRP (r=0.53), blood leukocytes (r=0.42), and the CDAI (r=0.38). Calprotectin was the only marker that could discriminate inactive endoscopic disease from mild activity (104+/-138 vs. 231+/-244 microg/g, P<0.001), mild from moderate activity (231+/-244 vs. 395+/-256 microg/g, P=0.008), and moderate from high activity (395+/-256 vs. 718+/-320 microg/g, P<0.001). The overall accuracy for the detection of endoscopically active disease was 87% for calprotectin (cutoff 70 microg/g), 66% for elevated CRP, 54% for blood leukocytosis, and 40% for the CDAI > or =150. CONCLUSIONS: Fecal calprotectin correlated closest with SES-CD, followed by CRP, blood leukocytes, and the CDAI. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which underlines its usefulness for activity monitoring.

Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies.

BACKGROUND: Symptoms of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can overlap. We aimed to determine the accuracy of fecal markers, C-reactive protein (CRP), blood leukocytes, and antibody panels for discriminating IBD from IBS and to define a "best test." METHODS: We prospectively included 64 patients with IBD (36 Crohn's disease [CD], 28 ulcerative colitis [UC]), 30 with IBS, and 42 healthy controls. Besides CRP and blood leukocytes, blinded fecal samples were measured for calprotectin (PhiCal Test, enzyme-linked immunosorbent assay [ELISA]), lactoferrin (IBD-SCAN, ELISA), Hexagon-OBTI (immunochromatographic test for detection of human hemoglobin), and LEUKO-TEST (lactoferrin latex-agglutination test). Blinded serum samples were measured for the antibodies ASCA (ELISA) and pANCA (immunofluorescence). RESULTS: Overall accuracy of tests for discriminating IBD from IBS: IBD-SCAN 90%, PhiCal Test 89%, LEUKO-TEST 78%, Hexagon-OBTI 74%, CRP 73%, blood leukocytes 63%, CD antibodies (ASCA+/pANCA- or ASCA+/pANCA+) 55%, UC antibodies (pANCA+/ASCA-) 49%. ASCA and pANCA had an accuracy of 78% for detecting CD and 75% for detecting UC, respectively. The overall accuracy of IBD-SCAN and PhiCal Test combined with ASCA/pANCA for discriminating IBD from IBS was 92% and 91%, respectively. CONCLUSIONS: The PhiCal Test and IBD-SCAN are highly accurate for discriminating IBD from IBS. There is only marginal additional diagnostic accuracy when the PhiCal Test and IBD-SCAN are combined with ASCA and pANCA. ASCA and pANCA have a high specificity for IBD.

Vitamin D Deficiency in Unselected Patients from Swiss Primary Care: A Cross-Sectional Study in Two Seasons.

BACKGROUND: As published data on 25-hydroxy-cholecalciferol (25(OH)D) deficiency in primary care settings is scarce, we assessed the prevalence of hypovitaminosis D, potential associations with clinical symptoms, body mass index, age, Vitamin D intake, and skin type in unselected patients from primary care, and the extent of seasonal variations of serum 25(OH)D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 25(OH)D was measured at the end of summer and/or winter in 1682 consecutive patients from primary care using an enzyme-linked immunosorbant assay. Clinical symptoms were assessed by self-report (visual analogue scale 0 to 10), and vitamin D deficiency was defined as 25(OH)D concentrations < 50 nmol/l. 25(OH)D deficiency was present in 995 (59.2%) patients. 25(OH)D deficient patients reported more intense muscle weakness (visual analogue scale 2.7, 95% confidence interval 2.5 to 2.9) and had a higher body mass index (25.9kg/m2, 25.5 to 26.2) than non-deficient patients (2.5, 2.3 to 2.7; and 24.2, 23.9 to 24.5, respectively). 25(OH)D concentrations also weakly correlated with muscle weakness (Spearman's rho -0.059, 95% confidence interval -0.107 to -0.011) and body mass index (-0.156, -0.202 to -0.108). Self-reported musculoskeletal pain, fatigue, and age were not associated with deficiency, nor with concentrations. Mean 25(OH)D concentrations in patients with vitamin D containing medication were higher (60.6 ± 22.2 nmol/l) than in patients without medication (44.8 ± 19.2 nmol/l, p < 0.0001) but still below the targeted level of 75 nmol/l. Summer and winter 25(OH)D concentrations differed (53.4 ± 19.9 vs. 41.6 ± 19.3nmol/l, p < 0.0001), which was confirmed in a subgroup of 93 patients who were tested in both seasons (p = 0.01). CONCLUSION/SIGNIFICANCE: Nearly 60% of unselected patients from primary care met the criteria for 25(OH)D deficiency. Self-reported muscle weakness and high body mass index were associated with lower 25(OH)D levels. As expected 25(OH)D concentrations were lower in winter compared to summer.

Association of adrenal function and disease severity in community-acquired pneumonia.

INTRODUCTION: Rapid and accurate risk stratification in patients with community-acquired pneumonia (CAP) is an unmet clinical need. Cortisol to dehydroepiandrosterone (DHEA) ratio was put forward as a prognostic marker in sepsis. We herein validated the prognostic value of the adrenal hormones DHEA, DHEA-Sulfate (DHEAS), cortisol/DHEA-, cortisol/DHEAS- and DHEA/DHEAS-ratios in patients with CAP. METHODS: We assessed severity of illness using the pneumonia severity index (PSI) and measured adrenal hormone concentrations in 179 serum samples of prospectively recruited patients hospitalized with CAP. We calculated spearman rank correlation, logistic regression analysis and Kaplan Meier curves to study associations of adrenal hormones and outcomes. RESULTS: There was a significant correlation between PSI score and total cortisol (r = 0.24, p = 0.001), DHEAS (r = -0.23, p = 0.002), cortisol/DHEA (r = 0.23, p = 0.003), cortisol/DHEAS (r = 0.32, p = <0.0001) and DHEA/DHEAS (r = 0.20, p = 0.009). In age and gender adjusted logistic regression analysis, cortisol (OR:2.8, 95% CI: 1.48-5.28) and DHEA (OR: 2.62,95% CI: 1.28-5.34), but not DHEAS and the different ratios were associated with all-cause mortality. The discriminatory accuracy of cortisol and DHEA in ROC analysis (area under the curve) was 0.74 and 0.61. In Kaplan Meier analysis, patients in the highest deciles of cortisol and DHEA (p = 0.005 and p = 0.015), and to a lesser extent of cortisol/DHEAS ratio (p = 0.081) had a higher risk of death. CONCLUSION: Cortisol, DHEAS and their ratios correlate with CAP severity, and cortisol and DHEA predict mortality. Adrenal function in severe pneumonia may be an important factor for CAP outcomes.

Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes.

BACKGROUND: The correlation between noninvasive markers with endoscopic activity according to the modified Baron Index in patients with ulcerative colitis (UC) is unknown. We aimed to evaluate the correlation between endoscopic activity and fecal calprotectin (FC), C-reactive protein (CRP), hemoglobin, platelets, blood leukocytes, and the Lichtiger Index (clinical score). METHODS: UC patients undergoing complete colonoscopy were prospectively enrolled and scored clinically and endoscopically. Samples from feces and blood were analyzed in UC patients and controls. RESULTS: We enrolled 228 UC patients and 52 healthy controls. Endoscopic disease activity correlated best with FC (Spearman's rank correlation coefficient r = 0.821), followed by the Lichtiger Index (r = 0.682), CRP (r = 0.556), platelets (r = 0.488), blood leukocytes (r = 0.401), and hemoglobin (r = -0.388). FC was the only marker that could discriminate between different grades of endoscopic activity (grade 0, 16 [10-30] µg/g; grade 1, 35 [25-48] µg/g; grade 2, 102 [44-159] µg/g; grade 3, 235 [176-319] µg/g; grade 4, 611 [406-868] µg/g; P < 0.001 for discriminating the different grades). FC with a cutoff of 57 µg/g had a sensitivity of 91% and a specificity of 90% to detect endoscopically active disease (modified Baron Index ≥ 2). CONCLUSIONS: FC correlated better with endoscopic disease activity than clinical activity, CRP, platelets, hemoglobin, and blood leukocytes. The strong correlation with endoscopic disease activity suggests that FC represents a useful biomarker for noninvasive monitoring of disease activity in UC patients.

Prognostic value of dehydroepiandrosterone-sulfate and other parameters of adrenal function in acute ischemic stroke.

BACKGROUND AND PURPOSE: Acute stroke has a high morbidity and mortality. We evaluated the predictive value of adrenal function testing in acute ischemic stroke. METHODS: In a cohort of 231 acute ischemic stroke patients, we measured dehydroepiandrosterone (DHEA), DHEA-Sulfate (DHEAS), cortisol at baseline and 30 minutes after stimulation with 1 ug ACTH. Delta cortisol, the amount of rise in the 1 ug ACTH-test, was calculated. Primary endpoint was poor functional outcome defined as modified Rankin scale 3-6 after 1 year. Secondary endpoint was nonsurvival after 1 year. RESULTS: Logistic regression analysis showed that DHEAS (OR 1.21, 95% CI 1.01-1.49), but not DHEA (OR 1.01, 95% CI 0.99-1.04), was predictive for adverse functional outcome. Neither DHEA (OR 0.99, 95% CI 0.96-1.03) nor DHEAS (OR 1.10, 95% CI 0.82-1.44) were associated with mortality. Baseline and stimulated cortisol were predictive for mortality (OR 1.41, 95% CI 1.20-1.71; 1.35, 95% CI 1.15-1.60), but only basal cortisol for functional outcome (OR 1.20, 95% CI 1.04-1.38). Delta cortisol was not predictive for functional outcome (OR 0.86, 95% CI 0.71-1.05) or mortality (OR 0.92, 95% CI 0.72-1.17). The ratios cortisol/DHEA and cortisol/DHEAS discriminated between favorable outcome and nonsurvival (both p<0.0001) and between unfavorable outcome and nonsurvival (p = 0.0071 and 0.0029), but are not independent predictors for functional outcome or mortality in multivariate analysis (adjusted OR for functional outcome for both 1.0 (95% CI 0.99-1.0), adjusted OR for mortality for both 1.0 (95% CI 0.99-1.0 and 1.0-1.01, respectively)). CONCLUSION: DHEAS and the cortisol/DHEAS ratio predicts functional outcome 1 year after stroke whereas cortisol levels predict functional outcome and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT00390962 (Retrospective analysis of this cohort).

Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes.

BACKGROUND: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown. The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin, Clinical Activity Index, C-reactive protein (CRP), and blood leukocytes. METHODS: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index. Patients and controls provided fecal and blood samples for measuring calprotectin, CRP, and leukocytes. RESULTS: Values in UC patients (n = 134) compared to controls (n = 48): calprotectin: 396 ± 351 versus 18.1 ± 5 µg/g, CRP 16 ± 13 versus 3 ± 2 mg/L, blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L (all P < 0.001). Endoscopic disease activity correlated closest with calprotectin (Spearman's rank correlation coefficient r = 0.834), followed by Clinical Activity Index (r = 0.672), CRP (r = 0.503), and leukocytes (r = 0.461). Calprotectin levels were significantly lower in UC patients with inactive disease (endoscopic score 0-3, calprotectin 42 ± 38 µg/g), compared to patients with mild (score 4-6, calprotectin 210 ± 121 µg/g, P < 0.001), moderate (score 7-9, calprotectin 392 ± 246 µg/g, P = 0.002), and severe disease (score 10-12, calprotectin 730 ± 291 µg/g, P < 0.001). The overall accuracy for the detection of endoscopically active disease (score ≥4) was 89% for calprotectin, 73% for Clinical Activity Index, 62% for elevated CRP, and 60% for leukocytosis. CONCLUSIONS: Fecal calprotectin correlated closest with endoscopic disease activity, followed by Clinical Activity Index, CRP, and blood leukocytes. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which emphasizes its usefulness for activity monitoring.

Accuracy of four fecal assays in the diagnosis of colitis.

PURPOSE: This study was designed to evaluate the accuracy of four different fecal markers in discriminating between irritable bowel syndrome, inflammatory bowel disease, and other forms of colitis and to examine the feasibility of collecting fecal samples in outpatients. METHODS: We prospectively included 20 patients with irritable bowel syndrome, 36 with inflammatory bowel disease (24 Crohn's disease, 12 ulcerative colitis), and 18 with other forms of colitis (8 infectious colitis, 5 ischemic colitis, 5 medication-induced colitis). Diagnosis was established by clinical, laboratory, and endoscopic workup. Blinded fecal samples were measured for calprotectin (PhiCal-Test, ELISA), lactoferrin (IBD-SCAN, ELISA), Hexagon OBTI (immunochromatographic test for detection of human hemoglobin), and LEUKO-TEST (lactoferrin latex-agglutination test). RESULTS: Overall accuracy for discriminating irritable bowel syndrome from inflammatory bowel disease or other forms of colitis was recorded, respectively: IBD-SCAN 91/100 percent, PhiCal-Test 89/100 percent, LEUKO-TEST 83/89 percent, Hexagon OBTI 77/84 percent, C-reactive protein 71/79 percent, and blood leukocytes 63/68 percent. Differentiation of inflammatory bowel disease from other forms of colitis with fecal markers was as follows: range of overall accuracy from 43 to 50 percent. Overall accuracy (in percent) for discrimination of irritable bowel syndrome from patients with Crohn's disease in remission (CDAI<150) was: IBD-SCAN 90, PhiCal-Test 90, LEUKO-TEST 85, Hexagon OBTI 77. Calprotectin and lactoferrin were significantly elevated in patients with Crohn's disease with CDAI>150 compared with those in remission. Fecal sampling feasibility in outpatients was high (acceptance rate 95 percent). CONCLUSIONS: IBD-SCAN and PhiCal-Test have the best overall accuracy for detection of colitis, followed by LEUKO-TEST, Hexagon OBTI, C-reactive protein, and blood leukocytes. Accuracy of fecal markers is high even in patients with Crohn's disease in remission. Fecal sampling feasibility was high in outpatients. Because fecal markers are unspecific, endoscopic workup remains crucial to determine the underlying cause of colitis.

Is there a clinical relevance of partial androgen deficiency of the aging male?

PURPOSE: Aging in men is characterized by a progressive, generally moderate decrease in plasma testosterone (T) levels and T substitution is increasingly prescribed. However, the association of partial androgen deficiency of the aging male with clinical symptoms and the ideal screening test are controversial. We investigate the association between various T measures and clinical and biochemical parameters of the aging male. MATERIALS AND METHODS: We investigated the association between total (TT), calculated free (FTcalc) and bioavailable (BT) testosterone, and various clinical and biochemical parameters in 51 healthy community living male volunteers, 55 and 75 years old. The parameters included serum levels of sex hormone-binding globulin, estradiol and lipid profile after an overnight fast; questionnaires assessing clinical symptoms, erectile function and mood; bone mineral density and body composition. RESULTS: TT correlated with FTcalc (r2 = 0.71, p <0.001) but not with BT (r2 = 0.04, p not significant) and FTcalc correlated moderately with BT (r2 = 0.23, p <0.001). Testicular volume correlated with TT levels (r2 = 0.17, p <0.001) and FTcalc (r2 = 0.17, p <0.001) but not with BT. There was neither a correlation of TT, FTcalc nor BT values with clinical symptoms nor with biochemical and radiological parameters, ie affective symptoms and sexual interest, circulating estradiol, lipid levels, bone mineral density or lean body mass. CONCLUSIONS: T values in our study sample did not correlate with clinical signs and symptoms of hypogonadism. Thus, according to our data, symptoms of the aging male could be rather multifactorial and should not be indiscriminately assigned to the age associated decrease in T levels.