Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT. Methods: IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cutoff. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p < 0.001). Serum IGF-1 SDS (OR = 1.926, p<0.001), BMI SDS (OR = 1.427, p = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ 2 = 18.088, p<0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Background The applicability and accuracy of artificial intelligence (AI)-assisted bone age assessment and adult height prediction methods in girls with early puberty are unknown. Objective To analyze the performance of AI-assisted bone age assessment methods by comparing the corresponding methods for predicted adult height with actual adult height. Materials and methods This retrospective review included 726 girls with early puberty, 87 of whom had reached adult height at last follow-up. Bone age was evaluated using the Greulich–Pyle (GP), Tanner–Whitehouse (TW3–RUS) and China 05 RUS–CHN (RUS-CHN) methods. Predicted adult height was calculated using the China 05 (CH05), TW3 and Bayley–Pinneau (BP) methods. Results We analyzed 1,663 left-hand radiographs, including 155 from girls who had reached adult height. In the 6–8- and 9–11-years age groups, bone age differences were smaller than those in the 12–14-years group; however, the differences between predicted adult height and actual adult height were larger than those in the 12–14-years group. TW3 overestimated adult height by 0.4±2.8 cm, while CH05 and BP significantly underestimated adult height by 2.9±3.6 cm and 1.3±3.8 cm, respectively. TW3 yielded the highest proportion of predicted adult height within ±5 cm of actual adult height (92.9%), with the highest correlation between predicted and actual adult heights. Conclusion The differences in measured bone ages increased with increasing bone age. However, the corresponding method for predicting adult height was more accurate when the bone age was older. TW3 might be more suitable than CH05 and BP for predicting adult height in girls with early puberty. Methods for predicting adult height should be optimized for populations of the same ethnicity and disease.

Background Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. Case presentation Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing’s syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. Conclusion PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Abstract Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT.Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups separately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA.Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.926, p＜0.001), BMI SDS (OR=1.427, p=0.001) and DHEAS SDS (OR=1.131, p=0.005) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237 ), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of advanced BA in obesity was significantly higher than that of normal weight and overweight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age, but IPT girls requiring further investigations show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT. Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cutoff. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups seperately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA. Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.642, p＜0.001) and DHEAS SDS (OR=1.125, p=0.021) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 18.9% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237 ), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of BA advancement in obesity was significantly higher than that of normal weight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affect BA advancement independent of BMI SDS. Conclusions: Chinese girls aged 4-8 years with IPT requiring further investigations might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Background and objectiveWith a worldwide trend to earlier age of onset of puberty, the prevalence of early-onset puberty (EP) among girls has increased. The impact of EP on the pattern of linear growth and bone maturation is unclear. Accordingly, the objective of our study was to describe this pattern for girls with EP in Shenzhen, China.MethodsA total of 498 untreated girls diagnosed with EP at Shenzhen Children's Hospital, China, between January 2016 and December 2021. A total of 1,307 anthropometric measurements and 1,307 left-hand radiographs were available for analysis. Artificial intelligence (AI) was used to determine bone age (BA). Participants were classified into groups according to chronological age (CA) and BA. The pattern of linear growth (height) and progression of bone maturation was described between groups using the Lambda-Mu-Sigma (LMS) method. Published height-for-CA and height-for-BA norm references for a healthy Chinese population were used for age-appropriate comparisons.ResultsThe mean CA of appearance of first pubertal signs (breast buds) was 8.1 ± 0.5 years. Compared to norm-referenced data, girls with EP were significantly taller at a CA of 7–10 years. This was followed by a slowing in linear growth after a CA of 10 years, with 71 girls with EP having already achieved their target adult height. From 7 to 10 years of BA, the linear growth was slower in the EP group compared to norm-reference values. This was followed by a period of catch-up growth at 11.2 years of BA, with growth curves approaching norm-referenced values. The BA progressed rapidly from 7 to 8 years of age in about half of the girls with EP (median ΔBA/ΔCA &gt;1.9), slowing, thereafter, until the period of catch-up growth at 11.2 years of BA.ConclusionsBA provides a more reliable reference than CA to assess growth parameters among girls with EP. Our limited data set does indicate that EP does not negatively impact final adult height. Therefore, the growth curves from our study are relevant, providing a reference for pediatricians in this clinical population and, thus, preventing over-treatment for EP.

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT. Methods: IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n=206) and control group (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). Serum IGF-1 SDS (OR=1.926, p＜0.001), BMI SDS (OR=1.427, p=0.001) and DHEAS SDS (OR=1.131, p=0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ2=18.088, p＜0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6–8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (Σ4DEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and Σ4DEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of Σ4DEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and Σ4DEHP in urine were independent risk factors for IPT progression, and Σ4DEHP may be associated with the progression of IPT to CPP or EP.