The phenotype of Graves' orbitopathy is associated with thyrotropin receptor antibody levels.

PURPOSE: Graves' orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO. METHODS: Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively. RESULTS: Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis. CONCLUSIONS: TSH-R-Ab were significantly associated with GO's phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.

Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves' orbitopathy.

PURPOSE: Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves' disease and Graves' orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated. METHODS: 91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays. RESULTS: Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (P < 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (P < 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615-9.457, P = 0.003; versus 2.133, 0.904-5.032, P = 0.084, univariate analysis; and OR 4.341, 95%CI 1.609-11.707, P = 0.004; versus 2.337, 0.889-6.145, P = 0.085 multivariate analysis). CONCLUSION: Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.

Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis.

UNLABELLED: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. INTRODUCTION: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. METHODS: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. RESULTS: After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. CONCLUSION: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis.

Reticulocyte haemoglobin content vs. soluble transferrin receptor and ferritin index in iron deficiency anaemia accompanied with inflammation.

Ferritin concentration, as a parameter of iron status that is commonly used in the diagnosis of iron deficiency anaemia (IDA), often has limited values if the iron deficiency is accompanied by inflammatory disease. This study evaluated the value of reticulocyte haemoglobin content (CHr) and soluble transferrin receptor-ferritin index (sTfR/F) in the diagnosis of IDA and differential diagnosis of IDA and anaemia of chronic disease. The study included 66 nonanaemic individuals as controls, 86 patients with IDA divided into noninflammatory and inflammatory subgroups, and 32 patients with anaemia of chronic disease. Blood count, iron, transferrin saturation, total iron binding capacity, ferritin, C-reactive protein, sTfR and CHr were determined. Receiver operator characteristic curve analysis showed very high discriminating power for CHr, soluble transferrin receptor (sTfR) and sTfR/F in the diagnosis of IDA. In patients with anaemia of chronic disease these parameters showed no significant difference from the control. CHr and sTfR enabled recognition of iron deficiency and were not affected by acute phase reaction. They are sensitive markers of body iron status with additional value to conventional tests for the detection of iron deficiency.

Changes in the plasma levels of protein C system parameters in pregnancy.

Resistance to activated protein C (APC) is a condition that leads to a hypercoagulative state with an increased risk for venous thrombosis. The aim of this study was to test the functionality of the protein C system in normal and complicated pregnancies and APC resistance. A total of 131 patients were tested, including pregnant women with normal and complicated pregnancies at different periods, e.g. from weeks 1 to 20, 21 to 30 and 31 to 38 of gestation. The following hemostatic parameters were determined: protein S, protein C, protein C Global and protein C APC sensitivity. Commercial "Behring" tests were used to determine the parameters of hemostasis. The values for protein C activity were within normal limits. Protein S values were below the lower limits. Significantly lower PC-NR (protein C normalized ratio) and APC-NR (activated protein C normalized ratio) values were found in all three of the gestation periods in pregnant women with a history of repeated miscarriages and hypertension in relation to pregnant women with normal pregnancies. In order to assess the diagnostic accuracy of investigated hemostatic parameters as markers of prethrombotic changes in pregnant women, the obtained values of investigated hemostatic parameters were evaluated by ROC analysis. PC-NR and APC-NR showed satisfactory diagnostic accuracy as markers of prethrombotic changes in pregnant women: more precisely, they were found to be good indicators of resistance to activated protein C in pregnancy.

Biochemical evaluation of patients with acute pancreatitis.

In this study we determined the clinical accuracy of alpha2-macroglobulin, alpha-amylase, C-reactive protein, lipase, non-esterified fatty acids, pancreatic alpha-amylase and phospholipase A in the diagnosis and prognosis of acute pancreatitis in a group of patients with acute abdominal pain using receiver operator characteristic curve analysis. We investigated 59 patients with acute pancreatitis and 72 patients with extrapancreatic diseases of gastrointestinal origin. On the basis of initial enzyme activities, at cut-offs of 245 U/l for amylase, 656 U/l for lipase, and 182 U/l for pancreatic alpha-amylase, the diagnostic efficiencies were 0.993, 0.980, and 0.975, respectively. Receiver operator characteristic curve analysis showed the same diagnostic accuracies. We evaluated the accuracy of serum alpha2-macroglobulin, C-reactive protein, non-esterified fatty acids and phospholipase A for differentiation between acute necrotizing pancreatitis and acute oedematous pancreatitis. C-reactive protein had the highest prognostic accuracy of the parameters studied (the area under curve = 0.9082) and at a cut-off value of 126 mg/l, sensitivity and specificity were 0.759 and 0.912, respectively. The role of the clinical laboratory in the investigation of patients with acute pancreatitis continues to evolve and biochemical parameters are a good diagnostic and prognostic option.