Serum Insulin-Like Growth Factor-1 (IGF-1) Age-Specific Reference Values for Healthy Adult Population of Serbia.

Context: Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population- and assay-specific reference values requires sizable representative cohort of healthy subjects. Subjects and Methods: In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5th - 95th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods. Results: IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use. Conclusions: Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI- and WHR-specific reference ranges. Population-based data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets.

Further studies on delineating thyroid-stimulating hormone (TSH) reference range.

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.

[Correlation of inflammatory cytokines in the urine and serum with clinico-laboratory and pathohistologic features in patients with IgA nephropathy]. / Korelacija koncentracije inflamacionih citokina u urinu i serumu s klinicko-laboratorijskim i patohistoloskim odlikama kod bolesnika s IgA nefropatijom.

Complete examination of 21 patients with IgA nephropathy included determination urine and serum IL-6, TNF alpha and INF gamma levels by ELISA (Luzernachen, Luzern Switzerland). Control group included 15 healthy volunteers. Urine IL-6 levels ranging 37-274.1 pg/ml were detected in 15 (71.2%) patients with IgA nephropathy. IL-6 serum levels were undetectable. In the control group serum and urine levels were also undetectable. Correlation between the IL-6 level and proteinuria degree and endogenous creatinine clearance rate has not revealed statistically significant relationship. In relation to histologic groups (minimal changes, focal glomerulonephritis, mesangial proliferative, diffuse sclerosing) patients with minimal changes had (statistically) significantly higher IL-6 urine levels than the third and fourth group. Average the urine levels were 145.8 +/- 166.6 pg/ml and the serum ones were 148 +/- 101 pg/ml. In relation to the control group (statistically) significant difference was not found. Correlation between TNF alpha level and proteinuria degree and creatinine clearance rate has revealed (statistically) significant relationship (p < 0.05). Average interferon gamma serum levels in lgA nephropathy patients were 312.0 +/- 111.8 and in comparison with the control group (statistically) significant difference was found (p < 0.01). The obtained results suggest the important role of cytokine production disregulation associated with the pathogenesis of IgA nephropathy.

[Serum and urinary interleukin-6 levels in patients with primary glomerulonephritis]. / Nivo interleukina sest u serumu i urinu bolesnika s primarnim glomerulonefritisom.

Several studies have suggested that the measurement of urinary interleukin-6 (IL-6) is a helpful tool for diagnosis and monitoring the progression of glomerulonephritis. The aim of this study was to determine if IL-6 level might reflect the histological type of glomerular lesions. We performed a prospective study of 43 patients who underwent renal biopsy in our hospital. There were 35 male and 8 female patients with median age of 30.5 years (range 19-50). Included among these were 13 cases of IgA nephropathy, 11 cases of membranoproliferative glomerulonephritis, 6 cases of poststreptococcal glomerulonephritis, 6 cases of mesangial proliferative glomerulonephritis, 5 cases of membranous nephropathy and 2 cases of C3 nephritis. IL-6 was measured by ELISA (Lucernachem, Switzerland). IL-6 was not detected in the serum and rine of 15 healthy controls. IL-6 was elevated in the urine of 30 patients with different histological types of glomerular lesions (range 3.7 to 433.3 pg/ml) but was not detected in the urine of remaining 13 patients. The presence of IL-6 in the urine in absence of raised serum IL-6 suggests that urinary IL-6 was produced by the kidney. We have concluded that urinary IL-6 level can be considered as a marker of glomerulonephritis but not one that is very specific for any particular histological type of primary glomerulonephritis. Thus, the urinary IL-6 level is not a useful tool in the differential diagnosis of primary glomerulonephritis. We need further studies to determine whether urinary IL-6 level could by considered for monitoring of disease activity and therapy.