Evaluation of interleukin-29 in autoimmune and inflammatory thyroid diseases.

OBJECTIVE: Interleukins play an important role in the development of autoimmune disorders. The aim of this study was to compare the concentration of interleukin-29 (IL-29) between healthy controls (CS) and patients with selected thyroid disorders: Graves' disease (GD), Hashimoto's thyroiditis (HT) and subacute thyroiditis (SAT). DESIGN AND METHODS: The following parameters were examined in the group of 95 individuals (45 with GD, 22 with HT, 28 with SAT) and 72 CS: thyroid hormones and autoantibodies, inflammatory markers and the concentration of IL-29 in serum. RESULTS: The concentration of IL-29 in the GD subgroup was higher than that in the CS subgroup [264.0 (62.5-1018.0) vs. 62.5 (62.5-217.0) pg/mL, P = .001]. We found no differences in IL-29 concentrations between the CS and HT or SAT subgroups. Multivariable linear regression analysis indicated that IL-29 was a statistically significant independent predictor of GD presence (r = 0.24; P = .003) after adjustment for TRAb (R2  = 0.45; P < .001). The ROC analysis of IL-29 at GD diagnosis revealed an IL-29 cut-off of 123 pg/mL (sensitivity: 0.689 and specificity: 0.625) as the best value, which significantly indicated the presence of GD [area under the ROC curve (AUC): 0.676; 95% confidence interval (CI): 0.574-0.778, P < .001]. CONCLUSION: This is the first study to demonstrate elevated IL-29 serum levels in patients with GD. Our results suggest that IL-29 might be engaged in one of the pathogenetic pathways of GD, but no HT and SAT. Future studies are required to evaluate the potential of the protein as a therapeutic target in GD.

Optimizing hepcidin measurement with a proficiency test framework and standardization improvement.

Objectives: Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization. Methods: We developed a pilot PT together with the Dutch EQA organization Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) that included 16 international hepcidin MPs. The design included 12 human serum samples that allowed us to evaluate accuracy, linearity, precision and standardization potential. We manufactured, value-assigned, and validated a high-level calibrator in a similar manner to the existing low- and middle-level sRM. Results: The pilot PT confirmed logistical feasibility of an annual scheme. Most MPs demonstrated linearity (R2>0.99) and precision (duplicate CV>12.2%), although the need for EQA was shown by large variability in accuracy. The high-level calibrator proved effective, reducing the inter-assay CV from 42.0% (unstandardized) to 14.0%, compared to 17.6% with the two-leveled set. The calibrator passed international homogeneity criteria and was assigned a value of 9.07±0.24 nmol/L. Conclusions: We established a framework for future PT to enable laboratory accreditation, which is essential to ensure quality of hepcidin measurement and its use in patient care. Additionally, we showed optimized standardization is possible by extending the current sRM with a third high calibrator, although international implementation of the sRM is a prerequisite for its success.

Evaluation of IL-29 in Euthyroid Patients with Graves' Orbitopathy: A Preliminary Study.

BACKGROUND: The most frequent cause of hyperthyroidism is Graves' disease (GD). Orbitopathy is the most prevalent and recognizable extrathyroidal manifestation of Graves' disease with unrevealed pathogenesis. Interleukin 29 (IL-29) is a relatively newly discovered inflammatory cytokine. Thus, the aim of this study was to evaluate the relationship between IL-29 and Graves' orbitopathy (GO) in euthyroid patients. METHODS: Thirty-one euthyroid patients with Graves' disease and with active GO [clinical activity score (CAS) ≥ 3/7], seventeen euthyroid patients with GD but without GO, and seventy-two healthy control subjects (CS) matched for age and gender were enrolled in the study. The following parameters were evaluated in every participant: thyroid-related hormones and autoantibodies and inflammatory markers (white blood cells, hsCRP). ELISA assay was applied to measure the concentration of IL-29. RESULTS: We found higher level of IL-29 in GO group in comparison with CS [165 (133-747) vs. 62 (62-217) pg/mL, p < 0.001]. Furthermore, participants in the subgroup with GD with GO as compared with GD without GO had higher concentration of IL-29 [165 (133-747) vs. 62 (62-558) pg/mL, p = 0.031]. The ROC analysis for IL-29 revealed IL-29 cut-off of 105 pg/mL (sensitivity 1.000 and specificity 0.597) as the best value significantly indicating the presence of GO in GD [area under the ROC curve (AUC): 0.739, 95% confidence interval (CI): 0.646-0.833, p < 0.001]. CONCLUSIONS: The present study revealed for the first time an elevated level of IL-29 in the serum of patients with GD and GO that might suggest its involvement in the pathogenesis of GD ocular complications.

Selected Organ and Endocrine Complications According to BMI and the Metabolic Category of Obesity: A Single Endocrine Center Study.

Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been referred to a single endocrine center. The study aimed to assess the prevalence of selected organ and endocrine complications by subdividing the group, firstly according to body mass index (BMI) and secondly with regard to metabolic syndrome (MetS), pre-MetS and the metabolically healthy obesity (MHO) category. We have observed that in our groups, the prevalence of hyperlipidemia, hypertension, asthma, obstructive sleep apnea (OSA) depended on BMI category, whereas the incidence of hyperlipidemia, hypertension, OSA, hypothyroidism, non-alcoholic fatty liver disease, prediabetes, and type 2 diabetes was related to the metabolic category. We concluded that the distribution of particular organ and endocrine complications change significantly with increased BMI and with the shift from MHO to pre-MetS and MetS. Thus, to determine the risk of organ and endocrine complications more effectively, BMI and metabolic status should be assessed during the examination of patients with obesity.

Iron Homeostasis and Hepcidin Concentration in Patients With Acromegaly.

Hepcidin is a protein responsible for maintaining iron (Fe) homeostasis. Data regarding the role of hepcidin in the pathomechanism of Fe balance disturbances associated with acromegaly (AG) are scarce. The aim of the study was to assess the impact of alterations in complete blood count parameters, Fe homeostasis, gonadal status and GH/IGF-1 on the level of hepcidin in AG patients. The study evaluated the differences in hepcidin concentration and iron homeostasis between patients newly diagnosed with AG in comparison to healthy control subjects (CS). We prospectively enrolled 25 adult patients newly diagnosed with AG and 25 healthy volunteers who served as CS. The level of hepcidin was measured using the Hepcidin 25 (bioactive) hs ELISA, which is a highly sensitive enzyme immunoassay for the quantitative in vitro diagnostic measurement (DRG Instruments GmbH, Germany). The median of hepcidin concentration in the serum of patients with AG was significantly lower 9.8 (6.2-18.2) ng/ml as compared to CS 21.3 (14.3-34.0) ng/ml (p = 0.003). In the AG group, a statistically significant negative correlation between hepcidin and IGF-1 (rho = -0.441) was observed. Our study demonstrated a decreased hepcidin level in AG patients in comparison to CS what may have a potentially protective effect against anemia through an increased bioavailability of Fe. Additionally, GH may have a positive direct or indirect effect on erythropoiesis. Further studies on larger patient groups are necessary in order to clarify the exact role of hepcidin in the regulation of erythropoiesis in the excess of GH/IGF-1.

Changes in complete blood count parameters influenced by endocrine disorders.

Complete blood count is one of the most common diagnostic methods used in everyday practice. Hormonal status is known to affect blood count parameters. The aim of this study is to summarize changes in blood count that may indicate endocrine disorders, based on a literature review. Red cell parameters deteriorate in thyroid disorders including autoimmune thyroiditis and tend to resolve with appropriate treatment implementation. The most frequent form of anaemia associated with thyroid dysfunction is normocytic anaemia. Macrocytic anaemia is more typical of autoimmune thyroiditis-induced hypothyroidism, while microcytic anaemia is more common in hyperthyroidism. Unexplained anaemia or an increase in red cell distribution width should prompt the investigation of thyroid disorders. Cushing's disease may manifest as an increase in white blood cells and platelets. In the blood smear, neutrophilia is often present, while lymphocytes and eosinophils may be within the lower normal range. Hypercortisolism may induce both hyperaemia and anaemia. In hypopituitarism, a decrease in red blood cell count, haemoglobin, haematocrit, and platelets is observed. Acromegaly may be accompanied by an increase in mean corpuscular volume of erythrocytes. Testosterone deficiency is manifested by a decrease in red cell parameters, whereas hyperandrogenism may lead to polycythaemia. In polycystic ovary syndrome an increase in white blood cell count reflects an underlying inflammatory state. Complete blood count analysis is an easily available and cost-effective additional tool in the diagnosis and treatment monitoring of endocrine disorders.

Changes in serum hepcidin according to thyrometabolic status in patients with Graves' disease.

INTRODUCTION: Hepcidin is an acute-phase protein and a key regulator of iron homeostasis. Anaemia frequently occurs in patients with thyroid dysfunction, and hepcidin may be a potential link. OBJECTIVES: Prospective assessment of hepcidin serum concentration and other parameters related to Fe homeostasis in hyperthyroid patients in the course of GD at diagnosis and during remission. PATIENTS AND METHODS: Out of 70 patients recruited, 42 (32 women, 10 men), aged 42.5±15.1 years, met the inclusion criteria. Clinical and biochemical assessment, including hepcidin measurement by ELISA, was performed at baseline (T0) and after restoration of euthyroidism (T1). RESULTS: Hepcidin concentration at T0 in the 24 patients who completed the study was significantly higher than the value during euthyroidism (28.7 (8.1-39.4) ng/mL vs. 7.9 (4.3-12.9) ng/mL, p<0.001). Hepcidin level was most significantly correlated with ferritin (rho = 0.723) in women at T0. In both men (377 (171-411) vs. 165 (84-237) ng/mL, p=0.001) and women (84 (23-104) vs. 35 (16-64) ng/mL, p=0.001), a significant decrease in ferritin level was demonstrated following therapy. A significant (p<0.001) increase in mean corpuscular volume (MCV) (83.5 (82.5-87.1) vs. 89.5 (88.8-90.0) fL) and mean concentration of haemoglobin (MCH) (29.0 (28.0-29.4) vs. 30.4 (29.5-31.1) pg) was observed. CONCLUSIONS: Hepcidin and ferritin decrease significantly during the transition from a hyperthyroid state to euthyroidism in patients with GD. The observed changes occur in parallel to iron homeostasis fluctuations. During the transition from the hyperthyroid state to euthyroidism, the improvement of haematological status is reflected mainly by the increase in MCV and MCH.

Novel Biochemical Markers of Neurovascular Complications in Type 1 Diabetes Patients.

Type 1 diabetes mellitus (T1DM) is associated with chronic complications, which are the result of neurovascular changes. There is still a lack of universal biochemical markers of microvascular damage. The present study aimed to investigate whether selected inflammatory proteins are related to the prevalence of microvascular complications in adult T1DM patients. The following markers were determined in a group of 100 T1DM participants: epidermal growth factor (EGF), metalloproteinase 2 (MMP-2), growth/differentiation factor 15 (GDF-15), and interleukin 29 (IL-29). Screening for microvascular complications, such as autonomic and peripheral neuropathy, diabetic kidney disease, and retinopathy, was conducted. The group was divided according to the occurrence of microvascular complications. At least one complication was required for the patient to be included in the microangiopathy group. The median EGF concentration in the microangiopathy group was higher than in the group without microangiopathy (p = 0.03). Increasing EGF concentration was a statistically significant predictor of the presence of microangiopathy in multivariate logistic regression analysis (p < 0.0001). Additionally, a higher GDF-15 level was associated with diabetic kidney disease, peripheral neuropathy, and proliferative retinopathy vs. nonproliferative retinopathy. GDF-15 concentration correlated negatively with estimated glomerular filtration rate (eGFR) (r = -0.28; p = 0.02). To conclude, higher EGF concentration is an independent predictor of the presence of microvascular complications in T1DM patients. Besides the relation between GDF-15 and diabetic kidney disease, it may be also associated with peripheral neuropathy and retinopathy.