Association between exposure to radioactive iodine after the Chernobyl accident and thyroid volume in Belarus 10-15 years later

Background While there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. Methods To assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. Results The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P < 0.001). Heterogeneity of association was observed by attained age (P < 0.001) with statistically significant association remaining only in the subgroup of ≥18 years at screening (P < 0.001). For this group, increase in dose from 0.0005 to 0.15 Gy was associated with a 1.27 ml (95% CI: 0.46, 2.07) increase in thyroid volume. The estimated effect did not change with increasing doses above 0.15 Gy. Conclusions This is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.

Rise and fall of thyroid radiologic density during the time course of amiodarone-induced thyrotoxicosis

Background and Objective It has been reported recently in a cross sectional study that patients with amiodarone induced thyrotoxicosis (AIT) showed a ‘white’ thyroid on unenhanced computed tomography, due to intrathyroid iodine accumulation. However, the link between increase in thyroid radiologic density and amiodarone induced thyrotoxicosis remains unknown. We sought to analyze this link. Methods We present the case of a 34-year-old patient with severe sarcoidosis-related hypertrophic cardiomyopathy who was followed with successive unenhanced CT scans integrated with FDG PET scans. After the first CT scans the patient, who initially had a normal thyroid function, was exposed to amiodarone during 23 months and developed AIT, very likely by thyroiditis (AIT type 2). There were no thyroid antibodies, no evidence of thyroid sarcoidosis on FDG PET scan, while thyroid sonogram showed a homogenous 22 ml moderate goiter with normal echogenicity and no nodules. Results Analysis of the successive enhanced CT scans revealed that after initiation of amiodarone treatment, thyroid radiologic density steadily increased before detection of AIT, peaked after cessation of amiodarone and initiation of thyrotoxicosis treatment, before returning to normal as thyrotoxicosis receded. Thyroid volume also showed a moderate increase, peaking at the detection of thyrotoxicosis, before returning to normal. Conclusion This case suggests that AIT is preceded by a very high intrathyroid iodine accumulation before the ‘burst’ of thyroiditis occurs and that measurements of thyroid gland radiological density might predict the development and remission of AIT.

Risk Factors for Subacute Thyroiditis Recurrence: A Systematic Review and Meta-Analysis of Cohort Studies

BackgroundSubacute thyroiditis (SAT) is a self-limited inflammatory thyroid disease with recurring episodes. However, the results regarding the recurrence rate and risk factors for SAT are inconsistent. This meta-analysis aimed to summarize the evidence of the recurrence rate and the risk factors for SAT.MethodsThe present study involved the performance of a systematic literature search of all English studies published in PubMed, Embase, Web of Science, and The Cochrane Library from inception to August 20, 2021. Cohort studies that reported the SAT recurrence rate and risk factors for recurrence were included. Two independent investigators extracted relevant information. Fixed- and random-effects models were used to pool effect sizes based on study heterogeneity.ResultsEighteen cohort studies were identified. The pooled findings showed that the recurrence rate was 12.0% (95% CI: 8.2%, 17.1%). The risk of recurrence in the glucocorticoids group was higher than that in the NSAIDs group (RR = 1.84, 95% CI: 1.04, 3.24). However, there was no significant difference in age or sex between the recurrence group and the non-recurrence group. Findings from one or two cohort studies also indicated that the copresence of HLA-B*18:01 and -B*35, the number of days required to taper prednisolone (PSL) to 5 mg/day, the duration of disease before treatment less than 30 days, the sialic acid level, or the TSH level at the termination of treatment and further extension of the hypoechoic area and increase in thyroid volume were related to the recurrence of SAT.ConclusionRecurrence was common in SAT patients. The present study indicated that glucocorticoid treatment was associated with a higher recurrence rate of SAT than NSAIDs treatment. The clinical implications of this association should be interpreted with caution, and further clinical trials on the long-term effects of different treatment strategies are needed.

Asynchrony of Apical Polarization, Luminogenesis, and Functional Differentiation in the Developing Thyroid Gland

Follicular thyroid tissue originates from progenitors derived from a midline endodermal primordium. Current understanding infers that folliculogenesis in the embryonic thyroid designates the latest morphogenetic event taking place after the final anatomical shape and position of the gland is established. However, this concept does not consider the fact that the thyroid isthmus develops chronologically before the lobes and also contains all progenitors required for lobulation. To elucidate whether cells committed to a thyroid fate might be triggered to differentiate asynchronously related to maturation and developmental stage, mouse embryonic thyroid tissues from E12.5-17.5 were subjected to immunofluorescent labeling of biomarkers (progenitors: NKX2-1; differentiation: thyroglobulin/TG); folliculogenesis: E-cadherin/CDH1; luminogenesis: mucin 1/MUC1; apical polarity: pericentrin/PCNT; basement membrane: laminin; growth: Ki67), quantitative RT-PCR analysis (Nkx2.1, Tg, Muc1) and transmission electron microscopy. Tg expression was detectable as early as E12.5 and gradually increased &gt;1000-fold until E17.5. Muc1 and Nkx2.1 transcript levels increased in the same time interval. Prior to lobulation (E12.5-13.5), MUC1 and TG distinguished pre-follicular from progenitor cells in the developing isthmus characterized by intense cell proliferation. Luminogenesis comprised redistribution of MUC1+ vesicles or vacuoles, transiently associated with PCNT, to the apical cytoplasm and the subsequent formation of MUC1+ nascent lumens. Apical polarization of pre-follicular cells and lumen initiation involved submembraneous vesicular traffic, reorganization of adherens junctions and ciliogenesis. MUC1 did not co-localize with TG until a lumen with a MUC1+ apical membrane was established. MUC1 delineated the lumen of all newly formed follicles encountered in the developing lobes at E15.5-17.5. Folliculogenesis started before establishment of a complete follicular basal lamina. These observations indicate that embryonic thyroid differentiation is an asynchronous process consistent with the idea that progenitors attaining a stationary position in the connecting isthmus portion undergo apical polarization and generate follicles already at a primordial stage of thyroid development, i.e. foregoing growth of the lobes. Although the thyroid isthmus eventually comprises minute amounts of the total thyroid volume and contributes little to the overall hormone production, it is of principal interest that local cues related to the residence status of cells – independently of a prevailing high multiplication rate – govern the thyroid differentiation program.

ANALYSING ASSOCIATION BETWEEN ANTHROPOMETRIC INDICATORS OF INSULIN RESISTANCE AND INSULIN-LIKE GROWTH FACTOR-1 IN PATIENTS WITH NODULAR GOITER

Publications suggesting that thyroid nodule might be associated with insulin resistance (IR) and metabolic syndrome are quite interesting. In a very recent report, increased thyroid volume and nodule prevalence were also reported in patients with IR in an iodine-sufficient area []. The purpose of the work is to analyze the association between anthropometric indicators IR and IGF-1 in patients with nodular goiter. Materials and methods. During the study the authors examined 73 patients with euthyroid single-node (n = 34) and multinodular goiter (n = 39) aged 17 to 74 years (mean - (51.0 ± 10.6) years), determining WC, WC / HC, BMI, WHtR, ABSI, BFD, BRI, CI, AVI, BAI, IGF-1, TSH, fT4, fT3. Thyroid volume, its structure, number, size and location of foci was assessed by an ultrasonic complex Aloka SSD-1100 (Japan), using a linear sensor 7.5 MHz. Results and their discussion. In the total number of patients with nodular goiter IGF-1 is nonlinearly negatively associated with BMI (r = -0.30; P = 0.016), WC (r = -0.26; P = 0.036), WHtR (r = -0.30) ; P = 0.020), AVI (r = -0.27; P = 0.03), ABSI (r = -0.31; P = 0.015), nonlinear positive with BFD (r = 0.27; P = 0.033) ), BRI (r = 0.29; P = 0.02) and linearly positive with BAI (r = 0.36; P = 0.004); thyroid volume is linearly positively associated with age (r = 0.35; P = 0.009), nonlinearly positively with WC / HC (r = 0.43; P = 0.001), BFD (r = 0.26; P = 0.06 ) and CI (r = 0.31; P = 0.02). In patients with nodular goiter with BMI≥35 kg / m2 thyroid volume is linearly positively associated with BMI (r = 0.71; P = 0.049). In patients with nodular goiter with IRF-1 above the sex-age norm, thyroid volume is nonlinearly positively associated with WC / HC (r = 0.71; P = 0.01), BAI (r = 0.66; P = 0.03 ) and nonlinearly negative with BFD (r = -0.52; P = 0.01). It has been found that BAI explains 82.37% of the variance of IGF-1 in the general group and more than 90% of the variance of its level in groups of patients with nodular goiter with high IGF-1 with / without obesity. In patients with nodular goiter with high IGF-1 and obesity, the predictor of increased thyroid volume is BRI, which explains 81.14% of the variance of its volume. Conclusions: Patients with nodular goiter with IGF-1 level in blood above the sex-age norm have significantly higher values ​​of anthropometric indicators IR (WHtR, ABSI, BFD and BAI) compared with patients with a normal level of this indicator; in patients with nodular goiter with II degree obesity and above, thyroid volume is significantly associated with BMI; BAI (R2 = 82.37%) is a predictor of increased levels of IGF-1 in blood of patients with nodular goiter, regardless of the obesity; BRI (R2 = 81.14%) is a predictor of increased thyroid volume in patients with nodular goiter with IGF -1 high level and obesity. Key words: nodular goiter, anthropometric indicators, insulin resistance

Age-specific correlation between thyroid hormone concentrations and ultrasound thyroid volume for diagnosing thyroid dysfunction in preterm infants: a single-centre, prospective, observational study protocol

IntroductionThyroid disorders are commonly concomitant with premature birth; however, indications to start therapy remain unclear due to lack of gestational age-specific reference ranges and thyroid ultrasound nomograms. We aim to evaluate the age-specific correlation between circulating free thyroxine (FT4) and thyrotropin stimulating hormone (TSH) levels and ultrasound thyroid volume to assist identify infants requiring thyroid hormone replacement therapy.Methods and analysisThis is an observational, prospective, single-centre study that will include 200 preterm infants born between 24 and 32 weeks of gestational age, without any congenital diseases or malformation that may affect thyroid function. Venous blood will be obtained in infants at 14–21 days of life, and at 32 and 36 weeks of postconceptional age (PCA) to measure FT4 and TSH concentrations. Thyroid ultrasound will be performed at 32 and 36 weeks of PCA. Relevant outcomes will include determination of FT4 and TSH values and ultrasound thyroid volume for preterm infants born at 24–28 weeks of gestation and 29–32 weeks of gestation. Correlations among circulating hormone concentrations and thyroid volumes with the head circumference and body mass will also be determined.Ethics and disseminationThe Ethics Committee of the Medical University of Warsaw has approved the study protocol prior to recruitment (KB44/2019). Informed consent will be obtained from caretakers of preterm infants at the time of enrolment. Consent for participation in the study can be withdrawn at any time, without consequences and without obligation to justify the decision. All data will be stored in a secure, password-protected Excel file that is only accessible to researchers involved in the study. Findings will be published in a peer-reviewed journal and disseminated at relevant national and international conferences.Trial registration numberNCT04208503.

Nutritional iodine status and obesity

Iodine is an essential component of the thyroid hormones, thyroxine and triiodothyronine. Its availability strictly depends on iodine content of foods, which may vary from very low to very high. Inadequate iodine intake (deficiency or excess) may affect thyroid function resulting in hypothyroidism or hyperthyroidism. Based on median urinary iodine concentrations, epidemiological criteria have been established for the categorization and monitoring of nutritional iodine status of a population (or subgroups of populations). Additional methods for iodine intake assessment include measurement of thyroid size (by thyroid palpation or ultrasonography) and of biochemical parameters, such as neonatal thyroid stimulating hormone, thyroglobulin and thyroid hormones.Recent studies carried out in overweight/obese children and adults provide evidence that body mass index (BMI) may significantly influence the above indicators, thus theoretically affecting the epidemiological evaluation of nutritional iodine status in populations.In this short review, we analyze current knowledge on the effects of overweight and obesity on indicators of adequacy and monitoring of iodine status, namely urinary iodine excretion and thyroid volume and echogenicity.Data on urinary iodine excretion in overweight/obese children are divergent, as both increased and reduced levels have been reported in overweight/obese children compared to normal-weight controls.Whether gastrointestinal surgery may affect iodine absorption and lead to iodine deficiency in patients undergoing bariatric surgery has been evaluated in a limited number of studies, which excluded iodine deficiency, thus suggesting that supplements usually recommended after bariatric surgery do not need to include iodine.Albeit limited, evidence on thyroid volume and obesity is consistent with a direct relationship between thyroid volume and BMI, irrespective of nutritional iodine status. Finally, a higher frequency of thyroid hypoechoic pattern has been described in overweight/obese children. This finding has been recently related to an increased adipocyte infiltration and thyroid parenchyma imbibition mediated by inflammatory cytokines and should be considered when the frequency of thyroid hypoechoic pattern is used as non-invasive marker to indirectly assess thyroid autoimmunity in monitoring Universal Salt Iodization programs. Further studies, specifically addressing the role of schoolchildren body mass index as a factor potentially influencing iodine intake indicators are needed.

Relationship between water iodine and children’s goiters

Excessive iodine can lead to goiters. However, the relationship between the water iodine concentration (WIC) and goiter rate (GR) is unclear. This study aims to explore the factors that influence children’s GR in areas with high WIC and analyse the threshold value of the GR increase associated with the WIC. According to the monitoring of the areas with high WIC in China in 2018–2020, a total of 54,050 children in eight high water iodine provinces were chosen. Drinking water, urine and edible salt samples of children were collected. The thyroid volume (Tvol) was measured. A generalized additive model (GAM) was used to analyse the relationship between the WIC and GR in children. Among the 54,050 children in areas with high WIC, the overall GR was 3.34%, the median of water iodine concentration (MWIC) was 127.0 µg/L, the median of urinary iodine concentration (MUIC) was 318 µg/L, and the noniodized salt coverage rate (NISCR) was 63.51%. According to the GAM analysis results, water iodine and urinary iodine are factors that influence the Tvol and GR, while the NISCR affects only the GR. When the WIC was more than 420 µg/L or the urinary iodine concentration (UIC) was more than 800 µg/L, the GR increased rapidly. When the NISCR reached more than 85%, the GR was the lowest. Thus, in areas with high WIC, WIC more than 420µg/L may increase the risk of goiter, and the NISCR should be increased to over 85% to avoid goiters in children.

Indicators of cognitive activity of children with laboratory hypothyroidism

The growth rate of a healthy child, the peculiarities of its physical and intellectual development, the formation of reproductive function are largely determined by the state of the endocrine system. Thyroid hormones have a significant impact on the growth and development of the child's organism. Today, attention is focused on the consequences of intellectual disabilities in children with hypothyroidism, as well as the impact of chronic iodine deficiency in the environment on the development of children. Insufficient intake of iodine in the body leads to congenital dysontogenesis of higher mental functions, to the formation, in severe cases, of mental retardation of varying degrees, and, in mild forms - to the borderline or partial disorders of intelligence. The aim is to study the cognitive functions of children with laboratory hypothyroidism. Methods. For a screening study of the intellectual development of school-age children living in geographical areas of Chernivtsi region (Ukraine) with varying degrees of iodine supply, 399 schoolchildren aged 11-18 years were studied, including 194 boys and 205 girls. The main group consisted of children (99) with laboratory hypothyroidism (HL), with thyroid stimulating hormone (TSH) elevation or with diverse complaints and who had been found to have elevated TSH levels during routine examinations. Patients with any kind of systemic disease and/or taking medications were excluded from the study. Diagnosis of HL was based on mild increase of TSH (5-25mIU/L) with a normal fT4 level. Thyrotropin-releasing hormone (TRH) test was also performed in all children. TSH response to TRH stimulation was considered to be normal when TSH levels were between 5-25 mIU/L. The formation of intellectual function was determined using a fragment of the R. Kettel test (adapted modified version of the children's personality questionnaire R. Kettel). Іnclusion сriteria: age 11-18 years, living in the Chernivtsi region, the absence of organic pathology of the CNS and mental retardation, diseases of the eyesight and hearing, for 6 months, all subjects did not receive any treatment with iodine-containing drugs and thyroid hormones. Results. Analysis of the study results showed that children, for the most part, have an average degree of intellectual development (60%). The level of intellectual formation changed in the direction of decreasing with increasing degree of iodine deficiency. Among children with laboratory hypothyroidism, the number of those who had a low level of intelligence was almost twice as high as in children from the comparison group 25 [21.8-27.3] % against 13 [11.8-16.6] %, P < 0.01). Children with laboratory hypothyroidism have a "debt" of 56% of attention, 36% of perception, 26% of motility, and 44% of memory. The pace of operating activities was reduced by 26%. Comparison of TSH concentration, ioduria and thyroid volume with the presence or absence of deficits in certain cognitive functions showed that in children with laboratory hypothyroidism and fine motor skills TSH G level was increased by 90%, thyroid volume by 28% , and with memory loss - 125% and 38%, respectively. Correlative analysis revealed a highly probable positive relationship between moderate strength in prepubertal children between thyroid volume and fine motor skills (r = 0.485, P < 0.01), memory (r = 0.488, P < 0.05) and efficiency (r = 0,321, P < 0,05). Conclusion. Children with subclinical hypothyroidism are characterized by decreased memory, instability of attention and decreased ability to concentrate, impaired fine motor skills, which generally reduces their mental capacity.