Vol 14, No 2 (2018)

De Gustibus
New adventures of the median urinary iodine
Gerasimov G.A.

Abstract

From the beginning of the 1990s until the end of the 2000s, Russian thyroidology developed under the auspice of “median ioduria”. The emergence of available techniques, such as urinary iodine analysis and the estimation of thyroid volume by ultrasonography, multiplied by the vast expanses of Russia, gave researchers an uncultivated field for epidemiological studies. In the course of the research, there were sometimes difficulties in interpreting the data identified in the epidemiological studies, which was partly due to the imperfection of the then existing international guidelines. In 2018, UNICEF and the Iodine Global Network (IGN) released updated recommendations based on an analysis of the experience and mistakes of the past 10–15 years. In his regular column, the author discusses new approaches to monitoring of iodine prophylaxis programs, in which the “median of ioduria” remains a central piece.

Clinical and experimental thyroidology. 2018;14(2):58-63
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Original Studies
Study of molecular basis of thyroid dysgenesis
Makretskaya N.A., Bezlepkina O.B., Kolodkina A.A., Kiyaev A.V., Vasilyev E.V., Petrov V.M., Chikulaeva O.A., Malievsky O.A., Dedov I.I., Tyulpakov A.N.

Abstract

Congenital hypothyroidism is a heterogeneous group of diseases, which is manifested by loss of function of the thyroid gland that affects infants from birth. 80–85% of cases are due to different types of thyroid dysgenesis. 5 genes have been described that are involved in the pathogenesis of thyroid dysgenesis: TSHR, PAX8, FOXE1, NKX2-1, NKX2-5.

Aims. To evaluate the prevalence of mutations in the genes TSHR, PAX8, FOXE1, NKX2-1, NKX2-5 among patients with severe congenital hypothyroidism.

Materials and methods. 161 patients (64 boys, 97 girls) with congenital hypothyroidism (TSH levels at neonatal screening or retesting greater than 90 mU/l) were included in the study. 138 subjects had different variants of thyroid dysgenesis, and 23 patients had normal volume of the gland. A next generation sequencing was used for molecular-genetic analysis. Sequencing was performed using PGM semiconductor sequencer (Ion Torrent, Life Technologies, USA) and a panel “Hypothyroidism” (Custom DNA Panel). Assessment of the pathogenicity of sequence variants were carried out according to the latest international guidelines (ACMG, 2015).

Results. 13 patients had variants in thyroid dysgenesis genes (8,1%, 13/161): TSHR, n = 6; NKX2-1, n = 3; NKX2-5, n = 1; PAX8, n = 3; FOXE1, n = 0.

Conclusions. Mutations in thyroid dysgenesis genes are a rare pathology. The majority of variants among our patients were identified in TSHR.

Clinical and experimental thyroidology. 2018;14(2):64-71
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The role of interleukins 17, 23 and antibodies to the thyroid-stimulating hormone receptor in the pathogenesis of endocrine ophthalmopathy
Charinzeva S.V., Taskina E.S.

Abstract

Background. Endocrine ophthalmopathy (EOP) is an autoimmune orbit disease characterized by soft retrobulbar tissues damage. The level of antibodies to the thyroid-stimulating hormone receptor (TSHRAbs) is considered as a laboratory marker of EOP activity. Interleukins 17 (IL-17) and 23 (IL-23) play an important role in the pathogenesis of some autoimmune diseases and directly correlate with clinical activity. At present, there is an open question about the role of these cytokines in EOP and their relationship with TSHRAbs.

Aims. To assess pathogenetic role of IL-17, IL-23 and TSHRAbs in patients with EOP.

Materials and methods. The study included 50 people (100 eyes) at the age of 43 [35; 50] years. Three study groups were formed: 32 patients with moderate severity of EOP (clinical group), 18 patients with thyroid pathology without EOP (comparison group) and 15 healthy subjects (control group). All groups were comparable in age and sex. The diagnosis was verified clinically, laboratory and instrumentally. A comprehensive ophthalmologic examination and blood sampling were performed to determine the concentrations of IL-17, IL-23 and TSHRAbs. Statistical processing of the data was carried out in the program “Statistica 10.0”, StatSoft, Inc.

Results. An increase in the level of TSHRAbs was observed in all phases of EOP activity in comparison with both comparison group and control (p < 0.05). But in the active phase TSHRAbs level reached the maximum values in 100% of patients. An increase in the IL-17 concentration in 5,3 times was found in the active EOP in comparison with the control group (p < 0.05). Concentration of TSHRAbs and IL-17 in blood serum directly correlates with EOP activity (p < 0.001). After carrying out pulse therapy with glucocorticosteroids, the consentration of IL-17 decreased almost to zero. There were no significant differences in the level of IL-23 in the groups (p = 0.56).

Conclusions. Determination of TSHRAbs and IL-17 levels in serum can be used as a laboratory diagnostic marker of EOP activity.

 

Clinical and experimental thyroidology. 2018;14(2):72-80
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The results of neonatal TSH screening do not agree with indicators of the optimal iodine status of pregnant women in the Republic of Georgia
Barnabishvilli N., Gerasimov G.A., Azikuri T.

Abstract

Background. Georgia historically was a country with moderate to severe iodine deficiency and high prevalence of endemic goiter. A representative countrywide iodine survey conducted in Georgia in 2017 confirmed optimal iodine nutrition of the population with median UIC 298 mcg/L in SAC and 211 mcg/L in PW.

Aim. The aim of this study was to assess status of iodine nutrition of population in Georgia.

Methods. The assesement based on the proportion of neonatal Thyroid-Stimulating Hormone (TSH) levels >5mIU/L from 2009 to 2015 and compare these data with the results of direct assessment of iodine status made during the 2017 national survey.

Results. From 2009 to 2015 the proportion of newborns with TSH >20 mIU/L decreased threefold: from 0.45 to 0.15%. This trend was observed in all regions of the country with significant difference between the capital city and Western in Eastern parts of the country. There has been also significant reduction of the prevalence of TSH >5 mIU/L in Georgia from 4.46% in 2009 to 3.5% in 2015. However, only in Tbilisi the frequency of elevated TSH was below 3% – the cutoff level for adequate iodine nutrition. In other regions (Western and Eastern Georgia) prevalence of TSH >5 mIU/L was 3.8% and 4.4% respectively that could be falsely interpreted as mild iodine deficiency.

Conclusions. Although neonatal TSH is useful to detect moderate to severe iodine deficiency, it should be cautiously recommended for the evaluation of iodine status in iodine sufficient to mildly iodine deficient regions.

Clinical and experimental thyroidology. 2018;14(2):81-85
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Review of literature
How to assess functional state of thyroid gland, and what should we do in situation when thyroid function tests are inadequate?
Melnichenko G.A., Rybakova A.A.

Abstract

In most cases, estimation of tests of the functional state of the thyroid gland does not cause difficulties. Often, according to results of hormonal research, we can conclude that there is a manifest (subclinical) hypothyroidism or a manifest (subclinical) hyperthyroidism. In these situations, difficulties in diagnosing and prescribing treatment to the patient usually do not arise. However, in clinical practice, can be a situation when the results of laboratory researches either do not correspond to clinical picture or do not correspond to the normal functioning of the pituitary-thyroid axis by the principle of log negative relationship. In such situations, quite often inadequate results can be explained by laboratory errors, effect of drugs or existence of genetic disease. Also, recently more and more questions arise in the diagnosis of the syndrome of euthyroid pathology. The correct algorithm of action in this situation will play a key role in diagnosing and identification of further tactics of patient management. In this study will be considered factors that lead to changes in laboratory researches and structured approach to assess functional state of the thyroid gland, which has big importance in clinical practice.

Clinical and experimental thyroidology. 2018;14(2):86-91
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Autoimmune polyglandular syndrome of adults: current ideas about predictors development of damage of a myocardium and diagnostics of components of a disease
Panevin T.S., Molashenko N.V., Troshina E.A., Golovenko E.N.

Abstract

The autoimmune polyglandular syndrome of adults (APS) is characterized by the damage of two and more endocrine glands leading more often to development of their hormonal insufficiency. The basis of most autoimmune endocrine diseases is lymphoid and macrophage infiltration of the target organ. Often in patients with one autoimmune disease, other components of the APS appear after a some time of latent period. Besides defeat organs of endocrine system which are including to the APS also not endocrine organs can be part of autoimmune defeat. Although defeat of cardiovascular system is not included in the structure of the APS, in some clinical cases development of damage of a myocardium in the absence of clinically shown damage of heart against the background of the combined autoimmune endocrine pathology is described. The saved-up clinical this development of damage of a myocardium on the background of autoimmune endocrine insufficiency and also laboratory and instrumental methods of diagnostics is presented in the review at this state. The most promising diagnostic methods for this condition are the determination of autoantibodies to myocardial components and magnetic resonance imaging of the heart. In clinical practice, it is possible to widely use the definition of antibodies to myocardium by indirect immunofluorescence, as well as using standardized immunoenzyme test systems.The saved-up clinical this development of damage of a myocardium on the background of autoimmune endocrine insufficiency and also laboratory and instrumental methods of diagnostics is presented in the review at this state.

Clinical and experimental thyroidology. 2018;14(2):92-99
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Clinical Guidelines
Guidance on the monitoring of salt iodization programmes and determination of population iodine status: Russian language version
 

Abstract

Over the last two decades, there has been remarkable progress towards eliminating iodine deficiency (ID). While there has been remarkable success, there have been several notable changes in the way that salt iodization programs have been designed and monitored, as well as the general landscape in which salt iodization is being implemented. This article is based on the “Guidance on the monitoring of salt iodization programmes and determination of population iodine status”. It summarizes important lessons learned on how to better track the performance of and refine salt iodization programs. The adequacy of iodine intakes should be examined among different subsets of the population (not only school-aged children), especially among groups vulnerable to deficiency (such as pregnant women). The acceptable range of ‘adequate’ iodine intake among school-age children can be widened from 100–199 µg/L to 100–299 µg/L eliminating the range of 200–299 µg/L that previously indicates ‘more than adequate’ iodine intake. The interpretation of mUIC of ≥ 300 µg/L as ‘excessive iodine intake’ remains unchanged. With currently available methods, the mUIC can only be used to define population iodine status and not to quantify the proportion of the population with iodine deficiency or iodine excess. National salt iodization programmes should monitor the use of iodized salt in processed foods. If the salt contained in such foods is well iodized, it can be an important source of iodine and may help explain iodine sufficiency in settings where household iodized salt coverage is low.

Clinical and experimental thyroidology. 2018;14(2):100-112
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Short messages
Gabriella Morreale de Escobar (1930-2017)
Gerasimov G.A.

Abstract

The obituary is dedicated to the memory of the outstanding scientist Gabriella Morreal de Escobar (1930–2017). She was known for many scientific discoveries in thyroidology, changing the view on the physiology and pathology of the thyroid gland.

Clinical and experimental thyroidology. 2018;14(2):113-114
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