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This study presents a case of familial transmission of thyroxine-binding globulin (TBG) deficiency. The SERPINA7-gene which codes for TBG is located on the X-chromosome (Xq21-22). More than 45 mutations have been reported to cause TBG- deficiency from various countries, but none from India so far. Genetic analysis of SERPINA7 gene was carried out to determine the cause of low TBG levels in one family. DNA samples of the propositus and the family members were subjected to Polymerase Chain Reaction (PCR) followed by direct sequencing. Allele-specific PCR and Next-gen sequencing (NGS) were employed to confirm the site of the mutation. Thyroid function tests were estimated by Radioimmunoassay (RIA) and Immunoradiometric assay (IRMA) kits. X-chromosomal inactivation status was analyzed in the female members harboring the mutation. A mutational screening in this family revealed a novel frame-shift mutation S353Q, 354fs3X in the exon 4 of the SERPINA7 gene which will be referred to as TBG-complete deficiency-India (TBG-CD-Ind). One out of four female family members harboring the mutation showed selective X-chromosomal inactivation. The affected family members were clinically euthyroid initially, showed changes in the thyroid function when tested after a long time span. However, the changes in the thyroid function in the affected family members had an autoimmune etiology. This study presents the first report of TBG-CD from India wherein a novel frameshift mutation referred to as TBG-CD-Ind (S353Q, 354fs3X) in the SERPINA7 gene was detected. No apparent association was identified between thyroid function and the TBG-mutation in the affected subjects. A detailed biochemical and genomic testing to determine the exact cause of discordant TFT in the patients would certainly aid in the unequivocal diagnosis of the thyroid function and for the precise individualized treatment.

Background. There are no data about the status of vitamin D and its effect on the growth hormone/growth factors axis in prepubertal children with intrauterine growth restriction (IGR). Of particular interest is a group of patients who remain significantly short on the background of a decrease in insulin-like growth factor 1 (IGF-1) levels and normal stimulated release of growth hormone (GH). The purpose of our study was to determine the levels of 25-hydroxycalciferol in the blood plasma of prepubertal children with short stature due to IGR on the background of normosomatotropinemia. Materials and methods. We examined 34 prepubertal children (14 girls and 20 boys) with short stature (average age — 6.95 ± 0.46 years) who had signs of IGR at birth. A symmetrical type of IGR was found in 15 (44.2 %) patients, an asymmetrical type — in 19 (55.8 %). According to the results of functional tests all patients had a normal GH peak release (> 10 ng/ml). Thyroid-stimulating hormone, free thyroxine levels in the blood plasma were determined by the immunoradiometric assay with standard Immunotech® kit (Czech Republic). At the time of examination, all patients were euthyroid. GH, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3) levels were determined by enzyme-linked immunosorbent assay using Immulite 2000 Xi kits (Siemens, USA). 25-hydroxycalciferol level was determined by the immunochemiluminescent method (Abbott, USA). The results were evaluated according to the guidelines of the International Society of Endocrinology (2011). Results. It was found that in prepubertal children with IGR signs at birth, the average height standard deviation score (SDS) at the time of the examination was –2.83 ± 0.12. There were no significant differences between the height and body weight in patients with a symmetrical and an asymmetrical types of IGR at the time of examination (p > 0.05). Vitamin D content in the blood plasma of children with IGR signs was 49.70 ± 2.17 nmol/l in the whole group. Vitamin D insufficiency below 75 nmol/l was found in 16 (47 %) patients, and vitamin D deficiency below 50 nmol/l — in 18 (53 %). No significant differences were found between vitamin D values in girls and boys with signs of IGR (51.79 ± 3.38 nmol/l and 48.36 ± 2.86 nmol/l, respectively, p > 0.05). Height SDS in the group of patients with an asymmetrical type of IGR weakly correlates (r = 0.38) with vitamin D content. Vitamin D level significantly differed depending on IGR type (in a symmetrical type — 44.1 ± 3.2 nmol/l, in an asymmetrical type — 54.20 ± 2.56 nmol/l, p < 0.05). IGF-1 SDS in the group of patients with an asymmetrical type of IGR weakly correlated (r = 0.36) with vitamin D level. On the background of a significant decrease in IGFBP-3 content in children with an asymmetrical type of IGR compared to those with a symmetrical type (–1.32 ± 0.07 SDS and –1.00 ± 0.14 SDS, p < 0.05), there was a reduction in IGF-1 levels (–1.62 ± 0.10 SDS and –1.34 ± 0.14 SDS, p = 0.05). Conclusions. Patients born with signs of IGR, even against normosomatotropinemia, may still have significant growth deficit, a sharp decrease in IGF-1 and IGFBP-3 for a long time after birth. The results obtained indicate the presence of hypovitaminosis D in all prepubertal patients who were born with the signs of intrauterine growth restriction. No correlation was found between vitamin D level and the maximum peak of stimulated growth hormone release. However, patients with an asymmetrical type of IGR have a weak correlation (r = 0.36) between IGF-1 SDS and vitamin D content, a significant decrease in the content of IGF-1, IGFBP-3, as well as vitamin D compared to its level in a symmetrical type of IGR. It is recommended to include the determination of vitamin D level in the blood plasma irrespective of the type of disease and the state of somatotropic function in the list of studies for the examination of children with short stature who were born with signs of intrauterine growth restriction.

Метою роботи було підвищення ефективності лікування дітей і підлітків із синдромом біологічно неактивного гормона росту (СБНГР) на основі вивчення вмісту есенціальних мікроелементів (ЕМ) у плазмі крові. Матеріали та методи. В дослідження включено 206 дітей і підлітків з різними формами низькорослості. Діти, хворі на СБНГР, увійшли до групи з 29 осіб (14,08 %): 21 хлопчик (72,41 %) і 8 дівчаток (27,59 %), відставання у зрості яких становило від –2,0 до –4,6 SD. Середній вік дітей — 9,01 ± 0,60 року. Діагноз СБНГР підтверджений наявністю нормальних/підвищених показників гормона росту (ГР) на тлі проведення стимуляційних тестів, різким зниженням рівня інсуліноподібного фактора росту 1 (ІФР-1) та позитивною пробою на чутливість до ГР. Мікроелементний статус оцінювали шляхом визначення рівнів ЕМ (цинку, селену, марганцю, хрому, міді) у плазмі крові методом рентгенофлуоресцентної спектрометрії за допомогою спектрометра ElvaX-med (Україна). Рівні ІФР-1 в плазмі крові визначали імунорадіометричним методом за допомогою стандартних наборів IRMA IGF-1 (Immunotech® kit, Чеська Республіка). Результати. В групі дітей з СБНГР рівень цинку становив 0,57 ± 0,04 мкг/мл, селену — 0,05 ± 0,01 мкг/мл, що вірогідно нижче, ніж у загальній групі дітей з низькорослістю (р < 0,001 та р < 0,05 відповідно). Середні рівні хрому та міді в плазмі крові були зниженими порівняно з показниками дітей з іншими формами низькорослості й становили 0,040 ± 0,003 мкг/мл і 0,79 ± 0,05 мкг/мл відповідно, та були вірогідно нижчими, ніж у дітей контрольної групи (р 0,01). Висновки. У пацієнтів із СБНГР встановлено вірогідне зниження рівнів цинку, селену, хрому та міді у плазмі крові. Отже, на наш погляд, до комплексу обстеження дітей з низькорослістю доцільно включати визначення рівнів ЕМ. При виявленні знижених рівнів ЕМ рекомендовано комбіноване лікування препаратами рекомбінантного ГР та такими, які містять відповідні ЕМ, що значно підвищує ефективність ріст-корегуючої терапії.

Determination of plasma aldosterone concentrations (PAC) and plasma active renin concentrations (ARC) is essential for the diagnosis of primary aldosteronism (PA). In Japan, although PAC and ARC are measured by radioimmunoassay and immunoradiometric assay, respectively, non-radioisotopic methods with better detection sensitivity, measurement accuracy, and technical simplicity are needed. We developed two-site sandwich chemiluminescent enzyme immunoassays (CLEIAs) to measure both PAC and ARC using monoclonal antibodies immobilized onto ferrite particles. The results of both assays are obtained simultaneously from a single plasma sample within 30 min using a fully automated system. The novel CLEIAs were validated using plasma samples from patients with PA (n = 52) and essential hypertension (n = 23). The PAC determined by the CLEIA was significantly correlated with that measured by liquid chromatography/mass spectrometry or conventional radioimmunoassay. The ARC determined by the CLEIA was significantly correlated with that measured by immunoradiometric assay. The limits of detection of the CLEIAs for PAC and ARC were 0.1 ng/dl and 0.04 pg/ml, respectively, which were better than those of conventional methods (PAC: 2.5 ng/dl; ARC: 5 pg/ml). The PAC and PAC/ARC ratio (ARR) were significantly higher, and the ARC significantly lower, in patients with PA than in those with essential hypertension. An ARR cut-off of 1.31 ng/dl per pg/ml showed a sensitivity of 96.2% and specificity of 78.3% for PA screening. The newly developed CLEIAs for measuring PAC and ARC could provide a clinically powerful alternative to conventional methods used for hypertension screening in clinical practice.

Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

Human insulin-like growth factor 1 (IGF-I) is the primary mediator of the effects of the growth hormone (GH). Therefore, it has been used as a biomarker to detect the abuse of GH in sports. The measurement of IGF-I relies on mass-based and immunological approaches to analysis. Among the mass-based analysis methods, liquid chromatography-mass spectrometry (LC-MS) has a number of functional advantages. LC-MS measurements based on the quantification of IGF-I, according to trypsin digestion, are used in the most common method of analyzing doping. However, this method is time-consuming and subject to experimental variability. In this study, we optimized a rapid method for detecting IGF-I without the trypsin digestion step. This method of analysis uses an ultra-centrifugal filter and an LC-HRMS through narrow-range mass scan method. To verify the validity of this method, eight categories of validation testing were applied with the following results: linearity, R2 > 0.99; limit of detection, 15 ng/ml; limit of quantification, 20 ng/ml; accuracy, >99%; recovery rate, >95%; carryover

Chromogranin A (CgA) is currently the most valuable tumor biomarker for diagnostic work-up, management and follow-up of neuro-endocrine tumors (NET). The aim of our study was to compare three different commercially available CgA ELISA kits and to evaluate their analytical and clinical performance. CgA was measured with three different commercial ELISA kits on leftover sera from 40 patients: Chromoa R assay (Cis), Hu chromogranin A ELISA (Dia), and Neolisa chromogranin A (Euro). Analytical and clinical performance was evaluated by measuring precision, area under the ROC curve, sensitivity, specificity, positive and negative predictive value, correlation coefficients and Passing and Bablok regression analyses. Precision (CV%) was acceptable for all evaluated ELISA's (Cis 10.3%; Dia 9.8%; Euro 14.5%). The area under the curve (AUC) was comparable between the three assays (Cis 0.693; Dia 0.627; Euro 0.721). Sensitivity varied between 41.2% and 64.7%. Specificity ranged between 69.6% and 82.6%. Pairwise comparison revealed significant systematic and proportional differences when comparing Cis versus Dia (Cis = 25.30 + 1.94 Dia) and Euro versus Dia (Euro = 26.54 + 1.92 Dia). Analytical and clinical performance was comparable for the three ELISA's. CgA results obtained with different ELISA's are not interchangeable.AbbreviationsCgA: Chromogranin A; ELISA: Enzyme-linked immunosorbent assay; IRMA: Immunoradiometric assay; NET: Neuroendocrine tumors; PPI: Proton-pump inhibitors; RIA: Radioimmunoassay.

We report a microarray immunoassay for thyrotropin in serum using an anti-thyrotropin monoclonal ‘antibody-chip’ fabricated on polycarbonate track-etched membranes as a solid-support. The thyrotropin microarray immunoassay is an immunoradiometric assay using 125I tracer and requires very small volumes of sample and reagents. The microarray immunoassay had the required minimum detection level, intra- and inter-assay CV and working range to be clinically useful. It correlated very significantly with commercial immunoradiometric assays for thyrotropin. We developed this microarray immunoassay for thyrotropin since it is often used as the first line test for thyroid function.

Aim: Type III collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type III procollagen (PIIINP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. Methods: Serum PIIINP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64 ± 11 years; dialysis duration, 11.5 ± 7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. Results: During the follow-up for 4.7 ± 1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PIIINP concentration (1 U/mL; hazard ratio, 1.616; P = 0.0001). The median serum PIIINP concentrations were higher in patients with cardiovascular events than in those without (2.30 ± 0.19 U/mL vs 1.30 ± 0.03 U/mL; P < 0.0001). When the patients were assigned to subgroups based on serum PIIINP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P = 0.0001) in the subgroup of serum PIIINP ≥ 1.75 U/mL than in that of serum PIIINP < 1.75 U/mL (31.9% vs 88.2%). Conclusions: Serum PIIINP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

Aim: Measurement of B-type natriuretic peptide (BNP) is widely used as a diagnostic and risk assessment tool for cardiovascular disease. Recent studies have demonstrated that BNP-32 and its precursor proBNP circulate in the blood stream, and that most commercial BNP immunoassays measure both forms. However, recombinant or synthetic BNP-32 is used as the standard for those BNP immunoassays. This gap between clinical samples and the standard might be a potential source of variation in BNP measurements among assays. The purpose of this study is to validate a more suitable calibrator for BNP immunoassays. Methods: External BNP calibrators containing both BNP-32 and glycosylated proBNP were prepared at two concentration levels. Target BNP concentrations of the low and high levels were 40 and 160 pg/mL, respectively. And to reflect clinical samples, the molar ratios of BNP-32 to glycosylated proBNP in these concentration levels were adjusted to 50:50 and 25:75, respectively. BNP concentrations of plasma samples along with the external BNP calibrators were measured at two commercial labs and using an automated analyzer MI02 Shionogi® BNP (MI02). These samples and the calibrators were also measured using an immunoradiometric assay (IRMA) as a standard assay procedure. Concentrations of the plasma samples measured at the labs or using the MI02 were adjusted according to a comparison of the measured concentrations of the external BNP calibrators with the IRMA. Results: After measured concentrations of the plasma samples were adjusted using the external BNP calibrators, the correlation between each measurement and the IRMA was improved. The range of the slopes according to Passing-Bablok regression analysis narrowed from 0.628 - 0.955 to 0.911 - 1.005. Conclusions: Our data suggests that a mixture of BNP-32 and glycosylated proBNP at different ratios by concentration level is suitable for calibration to minimize variations in BNP measurements among immunoassays.

Background Optimal vitamin D status has a great importance in puberty, which is a period of peak bone mineral acquisition. In this study, we aimed to assess the effect of pubertal period on vitamin D status. Methods The study included totally 200 healthy children, aged between 4 and 14 years. Group 1 included 100 prepubertal, children, aged between 4 and 8 years. Group 2 included 100 pubertal children, aged between 9 and 14 years. They had no chronic illnesses. Ages, heights, weights, genders, Body Mass Indexes (BMIs), socioeconomic and educational status of families were established. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured by high performance liquid chromatography (HPLC). Serum parathyroid hormone (PTH) was evaluated using an immunoradiometric assay kit. Serum calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured. Results We determined that 25(OH)D levels were lower with higher PTH levels in the group aged 9 to 14 years (pubertal children), compared to the group aged 4 to 8 (prepubertal children). Gender, weight, height or BMI, family socioeconomic and education status did not affect serum 25(OH)D levels of children in each group. Conclusions We demonstrated that vitamin D deficiency was more commonly seen in the pubertal children, compared to pre pubertal period. Children should be supported with vitamin D supplements during the puberty, which has a great importance for rapid increase in bone mass.

Purpose: Insulin-like growth factor 1 (IGF-1) is a trophic mediator that is regulated by growth hormone and associated with the proliferation, development, and growth of neural cells. IGF-1 may be associated with the pathophysiology of schizophrenia, but this association remains controversial. This study aimed to investigate the relationship between serum IGF-1 levels and psychiatric symptoms in patients with chronic schizophrenia.Patients and Methods: A total of 65 patients were recruited from the University of Occupational and Environmental Health, Komine Eto Hospital, Moji Matsugae Hospital, Shin-Moji Hospital, and Tsutsumi Hospital in Kitakyushu between September 2019 and June 2020. Further, 20 healthy age- and sex-matched control participants were recruited from the Komine Eto Hospital and the University of Occupational and Environmental Health. Patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale. Serum levels of free plus albumin-bound IGF-1 (IGF-1) were measured by immunoradiometric assay. The measurements were performed using antibody beads for bound/free separation. Associations between serum IGF-1 levels and the PANSS scores were determined. We also examined the associations between serum IGF-1 levels and diabetes, antipsychotic drug use, and disease duration.Results: No significant difference was found in the serum IGF-1 level between patients with schizophrenia and healthy controls. Serum IGF-1 levels were significantly negatively correlated with the PANSS total score (R2 = 0.06, p = 0.015) and PANSS general score (R2 = 0.088, p = 0.008), but not with the PANSS positive scores and PANSS negative scores. Serum IGF-1 levels were not related to the prevalence of diabetes (p = 0.64). However, a significant correlation was observed between serum IGF-1 levels and age (B = −1.88, p < 0.0001). Serum IGF-1 levels could not distinguish patients with schizophrenia and healthy controls.Conclusion: The association between serum IGF-1 levels and psychiatric symptoms may be complicated in patients with chronic schizophrenia.

WOS:000609589900001 PMID: 33445974 Purpose: This study aimed to evaluate the retinal blood vessel parameters and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with acromegaly in comparison with healthy controls. Methods: A total of 45 patients with acromegaly and 45 healthy controls were included in this study. In all patients, the vessel density (VD) of the deep and superficial macular vascular networks and the foveal avascular zone (FAZ) were measured using OCTA. The correlation of insulin-like growth factor 1 (IGF-1) level and disease duration with deep macular VD and FAZ values was analyzed. All parameters were registered. Results were assessed and compared between the two groups. Results: Deep macular plexus VD values were lower in patients with acromegaly compared to the control group. No significant differences in VD values in the superficial segment, except for that in the inferior parafovea (P = .01) were found between the two groups. Furthermore, patients with acromegaly showed enlargement in the superficial (P = .30) and deep FAZ areas (P < .001). IGF-1 level and disease duration showed a significant negative correlation with the deep whole image (R = -0.216, P = .041, R = -0.339, P = .001, respectively), deep parafovea (R = -0.271, P = .01; R = -0.372, P < .001, respectively), deep parafovea superior hemi (R = -0.342, P = .001; R = -0.350, P = .001, respectively), deep parafovea temporal (R = -0.224, P = .034; R = -0.234, P = .026, respectively), deep parafovea nasal (R = -0.320, P = .002; R = -0.361, P < .001, respectively), and deep parafovea superior VD values (R = -0.293, P = .005; R = -0.307, P = .003, respectively) and a significant positive correlation with the deep FAZ area values (R = 0.244, P = .02; R = 0.329, P = .002, respectively). Conclusion: VD values in the deep macular capillary plexus were lower in patients with acromegaly, and the superficial and deep FAZ area enlarged. Patients with acromegaly may have an increased risk of developing ocular vascular complications. OCTA can be used to evaluate retinal blood VD in patients with acromegaly.

Background: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. Methods: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. Results: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. Conclusions: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

Background: Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.Methods: Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).Results: This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P

It is very crucial to determine Tg accurately and precisely in thyroid cancer cases. Although there are many studies on the detection of Tg in thyroid cases in the literature, there are no sufficient clinical studies examining many cases with different features by using RIA methodology. Here, a radiometric and chromatographic method has been studied for the first time to eliminate the interference from anti-Tg positive patients. In this paper, radioimmunoassay (RIA) and immunoradiometric (IRMA) techniques were used for the analysis of 302 sera collected from patients for Tg and TgAb quantification. By the RIA technique, a reliable result was obtained by calculating the real Tg value quantitatively in 41 patients showing TgAb positivity out of 208 patients. Our findings show that the RIA assay is the most suitable approach for detection of changeable (low or undetectable) Tg value and metastases detected by post-therapeutic imaging in early-stage DTC cases showing preoperative and postoperative TgAb positivity. The new immunoradiometric method allows the real (%) Tg value to be reached in a part of TgAb-positive DTC. Even if TgAb positive in the metastatic and nonmetastatic DTC patient group. This allows the accurate clinical follow-up of patients.

As a rule, receptor-ligand assay data are fitted by logistic functions (4PL model, 5PL model, Feldman’s model). The preparation of the initial estimates for parameters of these functions is an important problem for processing receptor-ligand interaction data. This study represents a new mathematical approach to calculate the initial estimates more closely to the true values of parameters. The main idea of this approach is in using the modified linear least squares method for calculations of the parameters for the 4PL model and the Feldman’s model. In this study, the convergence of model parameters to true values is verified for the simulated data with different statistical scatter. Also, the results of processing real data for the 4PL model and the Feldman’s model are presented. A comparison is made of the parameter values calculated by the presented and a nonlinear method. The developed approach has demonstrated its efficiency in calculating the parameters of the complex Feldman”s models up to 4 ligands and 4 sites.

Introduction. Parathyroid hormone (PTH) is a linear peptide constituted by 84 amino acids and active in its 1–84 form, but a wide range of PTH forms produced by its post-transcriptional modifications are present in blood. Many assays with different specificities are commercially available. The aim of our study was to compare a 2nd and 3rd generation in healthy population in order to better define the reference range in the healthy population residing in our region. Materials and Methods. 108 subjects (53 females and 55 males) referring to the transfusion donor were enrolled in the study centre in April 2016 and underwent PTH levels measurements with a 3rd generation kit (chemiluminescent immunoassay DiaSorin Liaison) and with a 2nd generation kit (immunoradiometric assay Total Intact PTH Assay (Coated Tube), Scantibodies). Also calcium, phosphate, creatinine, and 25OHD3 were measured. A questionnaire on lifestyle and dietary habits was obtained. Results. The median PTH values obtained with the 2nd generation assay and the whole 3rd generation assay were 20.26 pg/ml and 23.11 pg/ml, respectively. Bland–Altman method showed substantial concordance between the two PTH assays, although with an overestimation of the 3rd generation method over the 2nd generation method. There was no correlation between 3rd generation PTH and 25OHD3 and creatinine. Calcium was negatively correlated with PTH only when measured with 3rd generation kit. Conclusions. On the basis of our data, obtained from healthy subjects, we can conclude that the reference range used by our laboratory was too narrow and was necessary to reestablish normal ranges according to our population. This is useful to avoid hyperparathyroidism misdiagnosis.

Background Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. Aim The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. Materials and methods The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. Results Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49–1236) pg/mL vs 67 (38–116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57–0.85, P = .039). Conclusion Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

An immunoradiometric assay (IRMA) procedure for estimation of prostate specific antigen (PSA) using coated tubes was developed, optimized, and validated. 125I-PSA and 125I-anti-hPSA tracers were prepared using iodogen and lactoperoxidase methods, respectively. Production of polyclonal anti-PSA was carried out using four New Zealand rabbits as a host. The polyclonal antibody was purified using caprylic acid/ammonium sulfate precipitation method. The coating was performed using the purified polyclonal antibody. The assay is highly sensitive and accurate.