Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Analysis of the distribution of adult height standard deviation scores in relation to prepubertal height standard deviation scores using longitudinal growth data: -Investigation of the catch-up rates of children with short stature to attain normal adult height.

Using the longitudinal growth data of 13,809 individuals in the Akita Prefecture, the percentage distributions of their adult height (AH) standard deviation scores (SDS) in relation to their prepubertal height SDS were obtained. The AH SDS increased with negative prepubertal height SDS and decreased with positive prepubertal height SDS, showing that a greater amount of change was associated with a greater interval of the prepubertal height SDS from the mean. The proportions of individuals who achieved normal AH stratified by prepubertal height SDS were as follows: 67.1%, in the group with prepubertal height SDS of -2.5 < to ≤ -2.0 SD, 46.0% in the group with -3.0 < to ≤ -2.5 SD, 75.2% in the group with +2.0 ≤ to < +2.5 SD, and 55.1% in the group with +2.5 ≤ to < +3.0 SD. Of all participants with short stature at prepuberty, 58.4%, 33.8%, 8.3%, and 0% of those with prepubertal height SDS of ≤ -2.0 SD, ≤ -2.5 SD, ≤ -3.0 SD, and ≤ -3.5 SD attained normal AH, respectively. On average, it is difficult for children with prepubertal height SDS of ≤ -2.5 SD to attain normal AH.

Confounding factors and biases involved in regional differences in the detection rate of thyroid cancer in the second-round Thyroid Ultrasound Examination: the Fukushima Health Management Survey.

In response to concerns about health due to radiation exposure, the Fukushima Prefecture launched the Thyroid Ultrasound Examination program for residents aged 0-18 years at the time of the earthquake. Herein, we considered the confounding factors involved in the regional differences in the development of thyroid cancer. In this study, the 242 065 individuals who participated in both first- and second-round surveys were classified into four groups by address according to their air radiation dose. The number of participants diagnosed as malignant or suspicious for malignancy by cytological examination were 17, 38, 10 and 4 with detection rates of 53.8, 27.8, 21.7 and 14.5 per 100 000 participants in Regions 1, 2, 3 and 4, respectively. Sex (P = 0.0400), age at the time of the primary examination (P < 0.0001) and interval between the first- and second-round surveys (P < 0.0001) were significantly different among the four regions, and these were suspected to be confounding factors affecting regional differences in malignant nodule detection rates. In addition, significant regional differences were observed in the participation rate in the confirmatory examination (P = 0.0037) and the fine needle aspiration cytology implementation rate (P = 0.0037), which could be potential biases. No significant regional differences in the detection of malignant nodules were found in the multivariate logistic regression analysis after adjusting for the survey interval alone or for sex, age and survey interval. The confounding factors and biases identified in this study that may have important impacts on thyroid cancer detection rate should be fully considered in future studies.

Low billing rates for pediatric sedation fee on magnetic resonance imaging.

BACKGROUND: The 2018 revision of social insurance in Japan allows additional fees to be calculated for pediatric magnetic resonance imaging (MRI) that must be performed under sedation. The number and trend of actual claims since this revision was established is unknown. The aim of this study to investigate the use of the additional fees and any regional differences in the use. METHODS: To analyze the claims of additional fees for pediatric sedated MRI after the fiscal year (FY) 2018, the actual claims in inpatient and outpatient practice was analyzed using publicly-available data from the Ministry of Health, Labour and Welfare (MHLW). We analyzed the calculation rate for all MRI scans. Annual changes in the actual number and calculation rate were analyzed. The ratio of the number of additional fees to the overall number of pediatric radiological procedures was used to examine the geographic disparity. RESULTS: The number of calculations from FY 2018 to FY 2020 was available. In FY 2020, only 1347 additional fees were calculated, corresponding to 0.35% of the total number of MRI scans. The number of fees showed a decreasing trend. Most cases were in the 0-4 year age group; however, there were a few cases in the 10-14 year age group without such a decrease. The relative number of calculations by prefecture showed an up to 14-fold disparity. CONCLUSIONS: The requirements for sedation for pediatric MRI are strict, but they are not fully utilized. Measures such as relaxing the requirements for the fee are needed to make MRI-related sedation safer.

Ultrasonography-based reference values for the cross-sectional area of the thyroid gland in children and adolescents: The Fukushima Health Management Survey.

We previously described the thyroid volume, which was calculated by measuring the thyroid width, thickness, and longitudinal length using ultrasonography, in children and adolescents. We have proposed a simplified method for quantitatively assessing the thyroid size, to overcome the inaccuracy and challenges in measuring the longitudinal length of the thyroid. Based on measurements of 317,847 (girls: 156,913, boys: 160,934) children and adolescents, we calculated sex-specific means and standard deviations of thyroid width and thickness, and of the cross-sectional area computed by multiplying them, for every age and 0.1 m2 of body surface area, after ensuring normal distribution with Box-Cox transformation. Multivariate regression analysis revealed that female sex, age, and body surface area were independently associated with areas of each thyroid lobe. Our novel method may be useful in quantitatively assessing the thyroid size, and appropriately diagnosing pathological conditions, such as hypoplasia, atrophy, and enlargement of the thyroid gland, in children and adolescents.

A Comprehensive Review of the Progress and Evaluation of the Thyroid Ultrasound Examination Program, the Fukushima Health Management Survey.

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents' anxieties about health risks due to radiation exposure for residents aged 0-18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Revisiting the Geographical Distribution of Thyroid Cancer Incidence in Fukushima Prefecture: Analysis of Data From the Second- and Third-round Thyroid Ultrasound Examination.

BACKGROUND: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. METHODS: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. RESULTS: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74). CONCLUSION: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.

Possible Association Between Thyroid Nodule Formation and Developmental Alterations in the Pituitary-Thyroid Hormone Axis in Children and Adolescents: The Fukushima Health Management Survey.

Background: We previously found low thyrotropin (TSH) levels in children and adolescents with thyroid nodules, including papillary thyroid cancer, although it is generally accepted that high TSH levels are a risk factor for formation and growth of thyroid nodules in adults. To clarify the reasons for the discrepancy, we precisely analyzed the features of pituitary-thyroid hormone (TH) actions in children and adolescents with or without nodules at different ages. Methods: Among the 4955 participants who participated in a second screening by thyroid ultrasound examination in the Fukushima Health Management Survey, 721 and 2849 euthyroid participants aged 6-20 years without or with nodules, including thyroid cancer, were selected for evaluation of TH regulation. The responsivity of TSH to THs was assessed by two thyroid feedback quantile-based indices (T4FQI and T3FQI). Logistic regression analyses were conducted to calculate the odds ratios (ORs) of serum concentrations related to thyroid functions for positive thyroid nodules compared with negative nodules. Results: The feedback indices declined in a sex-specific manner with aging. In particular, T3FQI, the index for TSH response to free triiodothyronine (fT3), started to decline after ∼10 and 15 years of age in female and male participants, respectively. Compared with the absence of nodules, the age- and sex-adjusted ORs (confidence intervals) for logTSH, free thyroxine (fT4), fT3, T4FQI, T3FQI, and thyroglobulin levels were 0.586 (0.501-0.685), 1.036 (0.595-1.805), 1.059 (0.842-1.332), 0.569 (0.454-0.715), 0.564 (0.443-0.719), and 1.01 (1.005-1.014), respectively. Associations between the presence of nodules and either low logTSH or low feedback indices were observed in participants aged between 12 and 17 years among the total cohort. Conclusions: The relationships between the levels of TSH and THs changed in a sex-dependent manner in children and adolescents. The age-dependent shift in the pituitary-TH set point may be associated with age-dependent nodule formation during restricted periods of growth and maturation in both young female and male participants.

Corrigendum to "Validation of auxological reference values for Japanese children with Noonan syndrome and comparison with growth in children with Turner syndrome".

[This corrects the article DOI: 10.1297/cpe.26.153.].

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Preschool-children's height, trend, and causes: Japanese national surveys 1990-2010.

We observed trends in the height of children aged 3 to 6 in Japan using data from the National Growth Survey on Preschool Children in the years 1990, 2000, and 2010. Average standard deviation (SD) scores of height decreased from 0.39 (SD 1.02) in 1990 (n = 3,684) to 0.37 (SD 1.05) in 2000 (n = 2,981) and 0.33 (SD 1.07) in 2010 (n = 2,027). Mothers of children in later waves were taller, older, and more likely to be primiparous; children in later waves had shorter gestational age, lower birth weight, and were less likely to have been fed less with formula or solid foods before 6 mo. The only factor that consistently contributed to a reduction in children's height for both 1990-2000 and 2000-2010 was a reduction in birthweight SD score (indirect effect on height -1.5 [95% CI: -1.9, -1.1] mm for 1990-2000 and -1.2 [95% CI: -1.8, -0.8] mm for 2000-2010). Factors that contributed, although not significantly or consistently between the two periods, were changes in pre-pregnancy BMI, smoking during pregnancy, multiple pregnancies, gestational age, BMI at birth, and use of formula and solid foods before 6 mo. Secular increases in maternal age, height, and primiparity contributed to increasing children's height.

Growth in girls with Turner syndrome.

Turner syndrome (TS) is a chromosomal disorder affecting females characterized by short stature and gonadal dysgenesis. Untreated girls with TS reportedly are approximately 20-cm shorter than normal girls within their respective populations. The growth patterns of girls with TS also differ from those of the general population. They are born a little smaller than the normal population possibly due to a mild developmental delay in the uterus. After birth, their growth velocity declines sharply until 2 years of age, then continues to decline gradually until the pubertal age of normal children and then drops drastically around the pubertal period of normal children because of the lack of a pubertal spurt. After puberty, their growth velocity increases a little because of the lack of epiphyseal closure. A secular trend in height growth has been observed in girls with TS so growth in excess of the secular trend should be used wherever available in evaluating the growth in these girls. Growth hormone (GH) has been used to accelerate growth and is known to increase adult height. Estrogen replacement treatment is also necessary for most girls with TS because of hypergonadotropic hypogonadism. Therefore, both GH therapy and estrogen replacement treatment are essential in girls with TS. An optimal treatment should be determined considering both GH treatment and age-appropriate induction of puberty. In this review, we discuss the growth in girls with TS, including overall growth, pubertal growth, the secular trend, growth-promoting treatment, and sex hormone replacement treatment.

Fine Needle Aspiration Cytology Implementation and Malignancy Rates in Children and Adolescents Based on Japanese Guidelines: The Fukushima Health Management Survey.

Background: The thyroid ultrasound examination (TUE) program was initiated among the residents of Fukushima Prefecture aged ≤18 years at the time of the Fukushima Dai-ichi Nuclear Power Plant accident. In this program, fine needle aspiration cytology (FNAC) was performed only in cases that conformed to the Japanese guidelines for the management of thyroid nodules. To analyze the suitability of the protocol in the TUE, we analyzed the implementation rate of FNAC and the detection rate of thyroid malignancy. Methods: There were 299,939 and 269,659 voluntary participants in the Preliminarily Baseline Survey (PLBS), first-round survey, and the first Full-scale Survey (FSS), second-round survey, of the TUE, respectively. FNAC is recommended for nodules with diameters 5.1-10.0 mm showing sonographic characteristics that are strongly suspicious for thyroid carcinoma; diameters 10.1-20.0 mm with characteristics that are suspicious for carcinoma; and all nodules with diameters >20 mm. Results: In the PLBS and the first FSS, 1362 and 1382 cases with thyroid nodules sized ≥5.1 mm in diameter were found, respectively. The implementation rates of FNAC in the PLBS were 20.1%, 63.2%, and 87.7% of subjects with nodules sized 5.1-10.0, 10.1-20.0, and ≥20.1 mm in diameter, respectively. In the first FSS, the FNAC implementation rates were 7.3%, 26.0%, and 50.0% in the subjects with nodules with diameters 5.1-10.0, 10.1-20.0, and ≥20.1 mm, respectively. In the subjects who underwent FNAC, the detection rates of malignant and suspected malignant nodules were 21.4% and 34.1% in the PLBS and first FSS, respectively. In the first FSS, malignant or suspected malignant nodules were found in 0.63% and 0.40% of subjects who had nodules of diameters ≤5.0 mm and 5.1-10.0 mm in the PLBS, respectively. In contrast, in the subjects with nodules measuring ≥10.0 mm in diameter in the PLBS, no malignancies were detected. Conclusions: The use of a protocol that conformed to the Japanese guidelines led to a reduction in the FNAC implementation rate and an increase in the malignancy detection rate in smaller nodules. In addition, the use of this strategy enabled us to avoid detection failure of thyroid carcinomas >10.0 mm.

Psychosocial support for the examinees and their families during the secondary confirmatory examination:Analyses of support records at first visit.

Background and Purpose The Thyroid Ultrasound Examination (TUE) program is conducted as part of the Fukushima Health Management Survey. Following the established criteria, examinees are called in for a secondary confirmation examination, which may induce high anxiety related to a thyroid cancer for both the examinees and their families. Therefore, Fukushima Medical University created the Thyroid Support Team to reduce anxiety. The purpose of this study is to analyze the psychosocial support for examinees and their families through two types of records, and to clarify the current issues and determine future directions of support.Materials and methods We analyzed 223 records of support for the first visit of examinees who attended the secondary confirmatory examination, conducted at Fukushima Medical University from September 2018 to March 2019.Results During the first visit, frequent topics and questions brought up by the examinees and their families were about the "Thyroid Ultrasound Examination (TUE) program" and "Examination findings". The Thyroid Support Team members assisted them by "Responding to questions", "Confirming the doctor's explanation" and "Providing information". The percentage of people with high anxiety decreased in both examinees and their family members after the examination. The level of anxiety was lower among those who had already taken the secondary confirmatory examination. Family members' anxiety was significantly higher than that of the examinees, and anxiety levels were highly correlated between examinees and their families.Conclusion The psychosocial support for examinees and their families was important in reducing their anxiety.　Currently there are changes in social conditions and various opinions concerning the TUE.　Thus, careful explanation and the need for decision-making supports for the examinees and their families increased. Also, we should take into account the aging of the examinees and expanding the available psychosocial support.

The current status of 492 adult women with Turner syndrome: a questionnaire survey by the Foundation for Growth Science.

Current status and its background of Adult Turner Syndrome (TS) are not clarified well. Via a questionnaire survey of 492 adult women with TS, this study investigated the association between menstruation, Kaufmann therapy (menstrual induction therapy), social status (education, employment & marriage), complications, transition from pediatric to adult care, and sex chromosome karyotype using statistical methods. Spontaneous menarche occurred in 22.0% and more frequently among patients with the 45,X/46,XX karyotype. Over 60% of these subjects, menstruation did not persist regularly. Kauffmann therapy was performed in 69.4%; the most common formulation was a conjugated estrogen and progesterone combination. Marriage and higher education advancement rates were low in adults with TS, whereas their employment rate was similar to that of the age-matched general female population. Patients receiving Kauffmann therapy had higher complication rates, greater education length, and higher employment rates. The higher-education advancement rate was observed among patients with 45,X/46,X,Xi and 46,X,Xi karyotypes. Transition from pediatrician to adult specialist was not smooth, subjects were treated in pediatric departments (60.7%), gynecological department (21.4%), internal medicine departments (13.3%), and others. While reason is not clear, the largest number of TS patients are treated in general pediatrics and the percentage of receiving Kauffmann therapy and having complication were significantly lower than in pediatric and adult department of endocrinology (& metabolism). This Study revealed many novel findings of adult TS.

Position paper from the Japan Thyroid Association task force on the management of low-risk papillary thyroid microcarcinoma (T1aN0M0) in adults.

The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.