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BACKGROUND: Pregnancy is a condition with important structural and physiological changes in the thyroid gland. In this regard, experts of thyroid associations have recommended developing specific reference intervals taking into account the natural and socio-geographical characteristics of the region under study.AIM: To conduct an epidemiological analysis and evaluate TSH reference intervals in pregnant women living in the central regions of the Russian Federation with mild iodine deficiency.MATERIALS AND METHODS: We have conducted the observational multicenter cross-sectional study included 2008 healthy pregnant women at different trimesters of pregnancy, from three regions of the Russian Federation (Moscow, Ivanovo and Smolensk). We assessed the level of thyroid-stimulating hormone, antibodies to thyroid peroxidase, antibodies to serum thyroglobulin, the level of iodine concentration in the morning portion of urine (cerium arsenic method) and we have conducted a questionnaire (date birth and gestational age). Women with elevated titers of anti-TPO and/or anti-TG antibodies were excluded from the study (245 women). As a result, we assessed high and medium levels of TSH and its overestimation with iodine sufficiency in pregnant women. The results are presented using the calculation of 2.5 and 97.5 percentiles.RESULTS: We confirmed the presence of iodine deficiency in the study areas. The median concentration of iodine in the urine was: in Moscow 106 μg/l, in Ivanovo 119 μg/l, in Smolensk 134 μg/l. Pregnant women were divided into 2 groups according to iodine adequacy. In the group with optimal iodine supply, the level of TSH was 0,006–3,36 in the 1st trimester, 0,20–3,74 in the 2nd trimester, and 0,33–3,68 mIU/L in the 3rd trimester. In the group with mild iodine deficiency — in the 1st trimester it was 0,11–3,00, in the 2nd trimester 0,22–3,78, in the 3rd trimester 0,07–3,04 mIU/l. Statistical analysis of the data revealed that when comparing the level of TSH by trimester, depending on the place of residence, no statistical difference was found (p = 0,239).CONCLUSION: We obtained that the level of TSH in healthy pregnant women living in the central regions of the Russian Federation does not exceed 3.8 mIU/l in all trimesters.

BACKGROUND: Graves' Orbitopathy (GO) — also known as Thyroid Eye Disease (TED) — is an autoimmune condition in the modern sense. It is closely associated with autoimmune thyroid diseases. Cytokine-mediated mechanisms play a critical part in immunopathogenesis of autoimmune thyroid diseases including GO. Investigating cytokine profiles as well as antibodies to tissue-specific antigens is essential for explaining GO pathogenesis and developing future therapeutic strategies.AIMS: The study examines serum levels of cytokines, autoantibodies and immunoglobulins IgG and IgG4 as mediators of autoimmune inflammation in patients with GO and Graves' Disease (GD).MATERIALS AND METHODS: The study included 52 patients (104 orbits) aged 25-70 years (mean age 48,8±12,3) in the active phase of GO and GD verified with the international diagnostic standards. These patients did not get any treatment for GO before. The control group consisted of 14 individuals (28 orbits) aged 30-68 years without known autoimmune disease.Serum levels of IgG, IgG4,TNFα, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-13, sIL-6R, sTNFα- RI и TNFα- R2 IL-2R, TGFβ1, TGF β3, antibodies to TSH-receptor, free T4, free T3 and TSH were measured. A diagnostic ultrasound exam of thyroid gland, multislice computed tomography (MSCT) / magnetic resonance imaging (MRI) of orbits were performed.RESULTS: Mean duration of GO prior to being admitted to the centre was 8,8±1,5 months (range: 1 — 48 months). According to the degree of thyrotoxicosis compensation: 24 patients were clinically euthyroid, TSH 3,3±0,7 mU/L, free T4 11,9±0,59 pmol/L, free T3 3,97±0,1 pmol/L; 28 patients were considered to have subclinical thyrotoxicosis: TSH 0,03±0,01 mU/L, free T4 14,2±1,0 pmol/L, free T3 5,77±0,49 pmol/L. Serum levels of sTNFα-R2 (p=0,041, p≤0,05), sIL-2R (p=0,020, p≤0,05), TGFβ1 (p=0,000, p≤0,001) were significantly higher in patients with GO compared to the control group. Serum levels of sTNFRα2 (p=0,038, p5%).CONCLUSION: High levels of soluble cytokine receptors sTNFα-R2 and sIL-2R and cytokine TGFβ1 in patients with long-standing untreated GO and GD being euthyroid or having subclinical thyrotoxicosis indicate activation of regulatory T cells aimed at suppressing autoimmune processes. High concentration level of IgG4 in IgG and cytokine TGFβ1 can determine the development of fibrotic changes in the orbital tissues. A decrease in the concentration of cytokine TGFβ1 can indicate an unfavorable course of the disease GO.

The testosterone is a key element of hypothalamus hypophysis gonad system. Its physiological role in males is well known and consists primarily in formation of male phenotype and support of spermatogenesis. The evaluation of androgenic status is necessary in case of such wide specter of clinical symptoms and pathological states as hypogonadism, delayed of premature puberty, polycystic ovary syndrome, particular types of cancer, etc. The precise measurements of testosterone concentrations have a decisive value in case of receiving biochemical data for supporting clinical decisions at diagnostic, treatment and prevention of androgenic diseases. The purpose of the study is to carry out a comparative analysis of the results of detection of testosterone in blood serum using analyzers Architect 2000 and Vitros 3600 and applying technique of highly-effective fluid chromatography - a tandem mass-spectrometry. The analysis was applied to samples of blood serum from 230 patients send to the endocrinological research center of Minzdrav of Russia. The comparative analysis of the results of detection of concentrations of testosterone demonstrated consistent difference in absolute values. However, a statistically significant correlation (р0,05) between values of testosterone obtained by different techniques was established. The correlation coefficient in different groups of patients made up to 0,894-0,920 and 0,955--0,965 correspondingly to comparing the results of Architect and Vitros and highly-effective fluid chromatography - a tandem mass-spectrometry. The calculated percentage of distribution of the results of detection of content of testosterone by the ranges of expected values demonstrated an admissible comparativeness of obtained results from point of view of practical diagnostic. The choice of technique of detection of biochemical parameters in case of primary diagnostic is very important. However, even more important is the application of the very same technique in treatment and long-term observation of patient.

The detection of free cortizol in day urine is an informative marker for diagnosing conditions of hypo- and hypercorticism. Up to 1% of cortizol, in invariable form and with no association with proteins and secreted by adrenal cortex, is excreted with urine during a day. The level of free cortizol in urine has no dependencies from day variation of hormone in blood and hence it reflects total secretion of cortizol by adrenal cortex. Besides, as a rule a direct proportional dependence exists between level of free cortizol in urine and level of biologically active cortizol in blood. The developers of automated systems propose various techniques of detecting cortizol not only in blood but in other biological fluids too. In our laboratory techniques of detection of level of free cortizol in day urine were approved, modified and adapted meant for analyzer Vitros ECi (Ortho Clinical Diagnostics, Great Britain) and analyzer Cobas 6000 (Hoffmann-La Roche, Switzerland). The comparison of results obtained by these techniques was carried out (r = 0,96-1). The reproducibility of detection of cortizol was evaluated by force of analysis of every sample of urine in one and various settings. The spread made up to 1,7-3,7% for one setting and 5,2-6,7% for various settings. The schemes were proposed to detect level of free cortizol in urine for analyzer Vitros ECi (with preliminary extraction by diethyl ether and subsequent removal of water fraction by force of freezing), and also for analyzer Elecsys (with preliminary extraction by dichlormethane and subsequent separation of phases by centrifugation and evaporation of organic phase by force of vacuum concentrator).

The objective of the present work was to estimate the possibility of using the ELISA technique for the quantitative analysis of the metanephrine and normetanephrine levels in urine and to determine the cross-off points for the discrimination between their normal and pathological values for the purpose of diagnostics of pheochromocytoma. Methylated derivatives of adrenaline and noradrenaline were measured in 3,234 urine sample obtained from the patients presenting with elevated arterial pressure, resistance to therapy, and adrenal mass lesions who had visited the inpatient and outpatient departments of the Endocrinological Research Centre during the past 4 years. The measurement of total metanephrine and normetanephrine (free plus deconjugated fractions) was performed using commercial ELISA kits (IBL, Hambutg, Germany). The content of normetanephrine over 612 mcg in daily urine samples was shown to be the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of this assay was 97,5% (95% CI 91,1-99,6%), specificity 100% (95% CI 93,8-100%). For metanephrine, the level of more than 550 mcg/24 hours was the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of the method was 100% (95% CI 88-100%), specificity - 96% (95% CI 86-99,4%). The biochemical diagnosis of pheochromocytoma was confirmed by the reference pathomorphological method in 99% of the cases. The incidence of pheochromocytoma predicted by the biochemical analysis of the urine samples delivered to the laboratory during 4 years from the patients with the tentative diagnosis of this pathology (based on the elevated arterial pressure and the presence of adrenal mass lesions) was 4% on the average. It is concluded that the application of ELISA in a "manual" mode provides high sensitivity and specificity of quantitative determination of metanephrines in daily urine comparable to those achieved with the widely used but more expensive high performance liquid chromatography.

The papers examines the specific features ofsteroidogenesis in the adrenal cortex ofpatients with different types of tumors and analyzes the ratio of ∆4- to ∆5-pathways of corticosteroid biosynthesis, which is a governing factor in the development of adrenal cortical hyperfunction. The levels of all major corticosteroids (cortisol, aldosterone, androgens of the adrenals) and their precursors were studied in the peripheral blood of patients with corticosteroma, aldosteroma, androsteroma, and hormonally inactive tumors (in the morning and in the evening). Based on the calculation of the mean daily concentration of steroids and the ratio of product/substrate of an enzymatic reaction in the biosynthesis of corticosteroids, the authors determined the activity of some enzymes and analyzed the changes found in this activity as compared with the normal values. The findings indicate that in corticosteroma, the higher activity of 11β-hydroxylase and the lower activity of 17,20-desmolase leads to a biosynthesis shift to ∆4-pathway; in virilizing tumor, the enhanced activity of Зβ-olsteroid dehydrogenase results in the same shift; in aldosteroma, the ratio of biosynthesis pathways does not differ from the normal values. The significant scatter in the individual values when the blood concentrations were determined in patients with hormonally inactive tumors fails to make an unambiguous conclusion about the activity of steroidogenic enzymes and about the direction of biosynthesis in these patients.

In most cases, current methods for immunoassay of blood total testosterone fail to provide a sufficient diagnostic accuracy. The authors measured the concentration of free testosterone in the blood and saliva samples from 189 males aged 19 to 83 years who had come to the clinic to confirm or exclude the diagnosis of various endocrine dysfunctions. Ultrafiltration had been previously carried on Amicon® Ultra membrane 30K filters (MILLIPORE) to determine the serum level of free testosterone. The ultrasensitive enhanced luminescence technique (IBL-Hamburg, Germany) was used to measure its concentration in the ultrafiltrate and saliva. The detection rate of androgen deficiency from the levels of free testosterone in the ultrafiltrate was higher than that from those of total testosterone and calculated free testosterone in blood. The preultrafiltration salivary and serum free testosterone values measured by the ultrasensitive enhanced luminescence technique may complement a sensitive marker of clinical symptoms to detect different forms of androgenic disorders.Современные методы иммуноанализа общего тестостерона в крови в большинстве случаев не обеспечивают достаточной диагностической точности. В данной работе мы определяли концентрацию свободного тестостерона в пробах крови и слюны 189 мужчин (19-83 лет), которые обращались в клинику для подтверждения или исключения диагноза различных нарушений функции эндокринных желез. Для определения уровня свободного тестостерона в сыворотке предварительно проводили ультрафильтрацию на фильтрах Amicon® Ultra-4 (MILLI-PORE) с мембраной 30К. Для измерения концентрации в ультрафильтрате и слюне использовали ультрачувствительный метод усиленной люминесценции (IBL-Гамбург, Германия). Процент выявления андрогенного дефицита по уровню свободного тестостерона в ультрафильтрате был выше, чем по уровню общего тестостерона и расчетного свободного тестостерона крови. Показатели свободного тестостерона в слюне и в сыворотке с предварительной ультрафильтрацией, измеренные ультрачувствительным методом усиленной люминесценции, могут служить дополнительным к клинической симптоматике чувствительным маркером для выявления различных форм нарушений андрогенного статуса.

To study the biocompatibility of porous glass ceramics, experiments were conducted on: 75 white mice (Vistar); 11 rabbits (Shinshila) and 6 dogs. The porous alumina ceramic implants were embedded subperiostaly without additional fixation to bone surface. The osseointegration of implants, the size and form maintaining, changing of physical properties and long-term results in bone substitution were studied. The handling properties during surgery were also evaluated.

To study prevalence and clinical implications of paradoxical rise of angiotensin II (AII) level in blood plasma in long-term therapy with ACE inhibitors in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy (DN).General clinical and hormonal (renin, AII, aldosteron, endothelin-1) examinations were conducted in 62 patients (37 males and 25 females) with DM-2 and DN on long-term ACE inhibitors. Escape of AII inhibition was defined as an increase in plasma AII more than 50 pg/ml corresponding to M+1SD in the control group (normotensive persons free of DM matched by age). Diet salt was controlled in all the patients.The patients received ACE inhibitors for 7.8 +/- 2.6 years. Plasma AII level in the control group was 34.5 +/- 16.1 pg/mL. The patients were divided into two groups according to their levels of AII: more than 50 pg/ml (group 1), less than 50 pg/ml (group 2). AII inhibition escape occurred in 24 patients (39%). No significant difference between the groups was registered by age, diabetes history, albuminuria, blood lipids, glycosylated hemoglobin, mean circadian blood pressure, duration of therapy with ACE inhibitors, intake of diuretics and beta-blockers. Patients of group 1 had a significantly higher cardiac interventricular septum thickness (p = 0.02), were more likely to have akinetic segments of the myocardium (p = 0.05), had lower 24-h urinary potassium (p = 0.03), insignificantly higher renal insufficiency. Plasma renin concentration was higher in group 1 (p = 0.004). AII did not correlate with aldosterone levels in both groups.A relatively large percentage of type 2 diabetics with DN is due to AII inhibition escape. It may explain the lack of reno- and cardioprotective effect of rennin-angiotensin-aldosterone system blockade.