ObjectiveResults of the screening of disease causative mutations in congenital hypothyroidism (CH) vary significantly, depending on the sequence strategy, patients’ inclusion criteria and bioinformatics. The objective was to study the molecular basis of severe congenital hypothyroidism, using the next generation sequencing (NGS) and the recent guidelines for assessment of sequence variants.Design243 patients with CH (TSH levels at neonatal screening or retesting greater than 90 mU/l) and 56 control subjects were included in the study.MethodsA custom NGS panel targeting 12 CH causative genes was used for sequencing. The sequence variants were rated according to American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsIn total, 48 pathogenic, 7 likely pathogenic and 57 variants of uncertain significance were identified in 92/243 patients (37.9%), while 4 variants of uncertain significance were found in 4/56 control subjects (7.1%). 13.1% (12/92) of the cases showed variants in ‘thyroid dysgenesis’ (TD) genes: TSHR, n = 6; NKX2-1, n = 2; NKX2-5, n = 1; PAX8, n = 3. The variants in ‘dyshormonogenesis’ (DH) genes were found in 84.8% (78/92) of cases: TPO, n = 30; DUOX2, n = 24; TG, n = 8; SLC5A5, n = 3; SLC26A4, n = 6; IYD, n = 1. 8 patients showed oligonenic variants. The majority of variants identified in DH genes were monoallelic.ConclusionsIn contrast to earlier studies demonstrating the predominance of TD in severe CH, the majority of variants identified in our study were in DH genes. A large proportion of monoallelic variants detected among DH genes suggests that non-mendelian mechanisms may play a role in the development of CH.

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Актуальность. В результате эпидемиологических исследований, проведенных в 2007 г., в г. Туринске Свердловской обла-сти была установлена избыточная концентрация йода в моче (медиана -1234 мкг/л) и высокая частота различной тире-оидной патологии у детей. Источником избыточного потребления йода предположительно являлась питьевая вода. Цель. Изучить последствия хронического избыточного потребления йода у населения Туринска. Материал и методы. Исследование проведено в двух городах Свердловской области: Туринске и Первоуральске. В обсле-дование было включено две группы детей: 97 в Первоуральске и 100 в Туринске, которые не различались между собой по возрасту, полу и площади поверхности тела, а также две группы взрослых по 100 человек в каждом городе, которые также были сопоставимы между собой по возрасту и полу. Всем испытуемым проводилось УЗИ щитовидной железы, у всех взрослых проводился забор венозной крови для определения тиреотропного гормона (ТТГ) и антител к тиреопероксида-зе, а у всех детей проводили забор капиллярной крови на фильтровальную бумагу для определения ТТГ и собирали разо-вую порцию мочи для определения концентрации йода. Концентрация йода также была исследована в 10 случайно ото-бранных образцах водопроводной воды, собранных в домохозяйствах Туринска. Результаты. Концентрация йода в водопроводной воде Туринска (629 мкг/л) в 5 раз превосходила предельно допустимую концентрацию. Медианная концентрация йода в моче в Туринске (719 мкг/л) была примерно в 6 раз выше, чем в Первоуральске -120,8 мкг/л. У детей из Туринска были установлены достоверно более высокие средние значения уровня ТТГ и частота диффузного зоба, чем у детей из Первоуральска. У взрослых добровольцев из Туринска по сравнению с испытуемыми из Первоуральска были установлены достоверно более высокие значения среднего уровня ТТГ, а также частоты субклинического гипотиреоза и аутоиммунного тиреоидита. Выводы. Подтвержден негативный эффект хронического избыточного потребления йода на функциональное состояние щитовидной железы и частоту тиреоидной патологии как у детей, так и у взрослых. Клю че вые сло ва: избыток йода, субклинический гипотиреоз, АИТ, диффузный зоб, ТТГ, содержание йода в моче, Туринск.Background. Previous surveys showed chronic iodine excess -median urinary iodine concentration (UIC) over 500 mcg/l -supposedly due to water contamination in population of Turinsk, a town in Sverdlovsk Region of Russia. Aim. Conduct an assessment of the effects of chronic iodine excess on thyroid function and spectrum of thyroid abnormalities in schoolchildren and adults. Materials and methods. Assessment was conducted in 100 schoolchildren and 100 adults residing in Turinsk and 97 schoolchildren and 100 adults in the control site (city of Pervouralsk) with optimal UIC. Assessment included thyroid ultrasonogrpahy, urinary iodine and dry spot TSH in schoolchildren and TSH and TPO-ab in adults. Iodine was also measured in random water samples from 10 households in Turinsk. Results. Median UIC in schoolchildren in Turinsk (719 mcg/l) was significan...

Childhood obesity is an urgent problem of pediatric endocrinology due to the widespread occurrence, the development of metabolic complications and their steady tracking into adulthood. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of obesity, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

BACKGROUND: Postprandial hyperglycaemia contributes significantly to the lack of glycaemic control in patients with type 1 diabetes mellitus (DM1). At least a quarter of patients forget to inject insulin before meals once a week, and more than 40% of them inject bolus insulin immediately before meals, which does not correspond to the pharmacokinetic effects of ultrashort insulins and determines the need to use insulins with better imitations of physiological insulin secretion.AIM: To assess the effect of fast acting insulin aspart (FIAsp) on the current parameters of glycaemic control in children with DM1 after switching from insulin Asp (iAsp) using continuous glucose monitoring.MATERIALS AND METHODS: A multicenter observational 12-week prospective open-label uncontrolled comparative study was initiated. A group of insufficiently controlled patients were identified (n = 48) including a group on multiple insulin injections therapy (MII) (insulin degludec and IAsp) and a group on continuous subcutaneous insulin infusion (CSII) of iAsp. Three 14-day flash glucose monitoring (FMG) were performed: before transferring patients to FiAsp and after 2 and 12 weeks of the transfer. Key endpoints: HbA1c after 2 and 12 weeks on FiAsp relative to baseline, analysis of 5 FMG target glucose ranges, presented as an ambulatory glycemic profile. Additional indicators: dynamics of insulin daily dose, frequency of glucose self- monitoring, the number of severe hypoglycemia, adverse events that occurred during treatment.RESULTS: 2 weeks after the transfer from IAsp to FIAsp, TIR increased in the entire group of patients: from 53% [44.3; 66.5] to 57% [47.4; 71.0] (p-value = 0.010) and TAR decreased from 38% [24.8; 50.2] to 30.5% [22.0; 45, 0] (p-value = 0.0124). Maintaining and increase time spent in the target glucose ranges during a 12-week observation period, in parallel with a significant decrease in hypoglycemic episodes <3.9 mmol / L per week, on FIAsp therapy naturally leads to an improvement in diabetes control: a decrease in HbA1c from 8.15% up to 7.75% (p-value = 0.0224), more pronounced in the group of patients on CSII — from 7.9% to 7.5% (p-value = 0.028).CONCLUSION: Switching from IAsp to BDIAsp in routine clinical practice in the MII and CSII regimen in children and adolescents with type 1 diabetes allows achieving better glycemic control compared to the previous generation prandial insulin analog Iasp. The better diabetes control is associated with an increase or a trend towards an increase in TIR and a decrease or a trend towards a decrease in TAR and TBR, as well as a significant decrease in episodes of hypoglycemia.