Ambient air pollution has been proposed as an important environmental risk factor that increases global mortality and morbidity. Over the past decade, several human and animal studies have reported an association between exposure to air pollution and altered metabolic and endocrine systems in children. However, the results for these studies were mixed and inconclusive and did not demonstrate causality because different outcomes were observed due to different study designs, exposure periods, and methodologies for exposure measurements. Current proposed mechanisms include altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation. In this review, we summarized the results of previous pediatric studies that reported effects of prenatal and postnatal air pollution exposure on childhood type 1 diabetes mellitus, obesity, insulin resistance, thyroid dysfunction, and timing of pubertal onset, along with underlying related mechanisms.

Objective We evaluated the frequency, risk factors and the follow‐up outcomes of thyroid nodules, and genetic alterations in thyroid cancer, in youth with childhood‐onset Hashimoto thyroiditis (HT) residing in an iodine‐sufficient country. Design A retrospective cohort study. Patients and measurements A total of 213 patients (194 females, mean age 10.6 years at the time of HT diagnosis) were ultrasonographically evaluated. Thyroid nodules were categorized using the Korean Thyroid Imaging Reporting and Data System (K‐TIRADS) and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR‐TI‐RADS). Results Thyroid nodules were detected in 40 (18.8%) patients over a median follow‐up period of 3.4 years, usually after the onset of puberty. A family history of thyroid disease (hazard ratio 2.1, p = .031) was predictive of thyroid nodule detection. Papillary thyroid carcinoma (PTC) was diagnosed in 9 (4.2% of all and 22.5% of nodule‐positive patients). The malignant nodules had a higher K‐TIRADS or ACR‐TI‐RADS risk level compared with benign nodules (p < .01 for both). Genetic alterations were revealed in 7 (BRAFV600E in 6 and RET‐ERC1 fusion in 1) of the eight available tumour tissue samples. None showed evidence of disease over a median follow‐up period of 3.4 years. Conclusions The nodule detection rate was 18.8%, with a 22.5% risk of malignancy among the detected nodules in childhood‐onset HT patients, showing increased risk in those with a family history. Additional large‐scale studies are required to evaluate the usefulness of K‐TIRADS or ACR‐TI‐RADS risk level for the differentiation of paediatric thyroid nodules.

Mitotane is an adrenolytic drug that exhibits a therapeutic effect within a narrow target range (14-20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair; she was diagnosed with an adrenal mass that was then excised. The Pathological result was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was commenced. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also commenced. However, the patient showed elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty in concentration. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane levels are elevated.Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by elevated mitotane levels. The mitotane levels decreased to sub-therapeutic levels several months after discontinuation of mitotane, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) also developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient; the drug dose should be individualized with frequent monitoring of the therapeutic level.

Objectives Vitamin D is essential for bone health. Not only total but also free 25-hydroxyvitamin D (25OHD) may contribute to bone mass. We sought to determine which vitamin D measure best reflected clinical and bone parameters in healthy children. Methods A cross-sectional study including 146 healthy children (71 boys, 9.5 ± 1.9 years) conducted at a tertiary medical center. We used a multiplex liquid chromatography-tandem mass spectrometry-based assay to simultaneously measure vitamin D metabolites. The bioavailable and free 25OHD (25OHDBioA and 25OHDFree) levels were calculated using the genotype-specific or genotype-constant affinity coefficients of vitamin D-binding proteins (yielding spe-25OHDBioA, spe-25OHDFree and con-25OHDBioA, con-25OHDFree respectively). The 25OHDFree level was directly measured (m-25OHDFree). Bone mineral content (BMC) and bone mineral density (BMD) were assessed via dual-energy X-ray absorptiometry. Results The total 25OHD (25OHDTotal), the two forms of 25OHDBioA, the three forms of 25OHDFree, and 24,25-dihydroxyvitamin D3 levels correlated with parathyroid hormone level (all p < 0.01). Serum 25OHDTotal and m-25OHDFree levels were influenced by age, pubertal status, season, body mass index (BMI), daylight hours, and vitamin D intake (all p < 0.05). The con-25OHDBioA and con-25OHDFree levels better reflected pubertal status and daylight hours than did the spe-25OHDBioA and spe-25OHDFree levels (both p < 0.01). The association between the 25OHDTotal level and bone parameters varied according to the BMI (interaction p < 0.05). In 109 normal-weight children, the con-25OHDBioA and con-25OHDFree levels correlated with total body BMC and BMD (both p < 0.05), whereas the 25OHDTotal and 24,25-dihydroxyvitamin D3 levels were associated with total body BMC (both p < 0.05). No such association was found in overweight or obese children. Conclusions In healthy children, total, bioavailable, and free 25OHD levels comparably reflected lifestyle factors. In normal-weight children, the con-25OHDBioA and con-25OHDFree, but not m-25OHDFree levels, reflected bone mass, as did the 25OHDTotal level.

Background: We investigated iodine status and its association with thyroid function among preschool children residing in iodine-sufficient area. Methods: From the Environment and Development of Children study, 477 children were evaluated for thyroid function and urine iodine concentration (UIC) at age 6 during 2015-2017. After excluding children born with multiple birth and with congenital hypothyroidism or Hashimoto thyroiditis, 439 (231 boys) were included. Subclinical hypothyroidism (SCH) was defined as thyroid stimulating hormone (TSH) levels between 4.9-10 μIU/mL with normal free T4 levels. Iodine status was evaluated by UIC and children were categorized into 4 groups: iodine deficient (UIC &lt; 100 μg/L), adequate (UIC, 100-299 μg/L), mild excessive (UIC, 300-999 μg/L), severe excessive (UIC ≥ 1000 μg/L). Results: Goiter was palpated in 64 (14.6%) with female predominance (26.0% vs. 4.3%, P &lt; 0.001). Serum level of free T4 and T3 was 1.2 ± 0.1 ng/dL and 148.1 ± 18.5 ng/dL, respectively. The median TSH level was 2.3 (0.53-8.59) μIU/mL and the prevalence of SCH was 4.3% without sex-difference. The median UIC level was 606.2 (19.9-16409.7) μg/L, higher in boys (684 vs. 545 μg/L, P = 0.021) than in girls. Iodine was deficient in 19 (4.3%), adequate in 96 (21.9%), mild excessive in 170 (38.7%), and severe excessive in 145 (35.1%). After excluding 19 iodine deficient children, the relationship between iodine status and thyroid function was evaluated by multiple regression analysis after adjusting for age, sex, birth weight, gestational age, body mass index Z-score, and family history. As iodine status increased from adequate, mild excessive to severe excessive group, T3 levels decreased, and TSH levels increased with marginal significance (P for trend &lt; 0.1 for T3 and TSH). When stratified by sex, similar association was found in only girls (P for trend = 0.043 for T3, and 0.062 for TSH) but not in boys, and mild excessive group showed lower free T4 levels (β = -0.05, P = 0.013) and severe excessive group had lower T3 levels (β = -7.04, P = 0.035) than iodine adequate group in only girls, but not in boys. Conclusion: Iodine was deficient in 4.3%, adequate in 21.9%, and excessive in 73.8% among preschool children residing in South Korea. As iodine status increased from adequate to excessive group, TSH levels increased with decreasing free T4 and T3 levels in girls.