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Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
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Objectives
Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood.
Methods
This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated.
Results
Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT.
Conclusion
Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan
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Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan
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Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
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Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
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Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan
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Objective
Ultra-sensitive hormone assays have detected slight sex differences in blood estradiol (E2) levels in young children before adrenarche. However, the origin of circulating E2 in these individuals remains unknown. This study aimed to clarify how E2 is produced in young girls before adrenarche.
Design
This is a satellite project of the Japan Environment and Children’s Study organized by the National Institute for Environmental Studies.
Methods
We collected blood samples from healthy 6-year-old Japanese children (79 boys and 71 girls). Hormone measurements and data analysis were performed in the National Institute for Environmental Studies and the Medical Support Center of the Japan Environment and Children’s Study, respectively.
Results
E2 and follicle stimulating hormone (FSH) levels were significantly higher in girls than in boys, while dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels were comparable between the two groups. Girls showed significantly higher E2/testosterone ratios than boys. In children of both sexes, a correlation was observed between E2 and testosterone levels and between testosterone and DHEA-S levels. Moreover, E2 levels were correlated with FSH levels only in girls.
Conclusions
The results indicate that in 6-year-old girls, circulating E2 is produced primarily in the ovary from adrenal steroids through FSH-induced aromatase upregulation. This study provides evidence that female-dominant E2 production starts several months or years before adrenarche. The biological significance of E2 biosynthesis in these young children needs to be clarified in future studies.
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Objective
To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty (CPP) in girls.
Method
Thirty four individuals with CPP, 17 individuals with premature thelarche (PT), and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case–control study. Physical measurements included BMI and tests for breast, bone, and sexual characteristics. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3, and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90, and 120 min after injection with triptorelin.
Results
Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P = 0.020), while serum MKRN3 levels were lower in the two groups (P = 0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P > 0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5.
Conclusions
Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.
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Background
The association between central obesity and cardiometabolic complications justifies exploring its association in normal-weight and overweight/obese (OW/OB) schoolchildren.
Objective
To describe cardiometabolic markers in four groups according to BMI/WC categories: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB, in a sample of Argentinean schoolchildren.
Methods
A cross-sectional study of 1264 Argentinean schoolchildren (624 F), aged 9.5 ± 2.2 years was performed between November 2013 and 2015. Children’s anthropometric measures, blood pressure (BP), glucose, lipids, and insulin were measured. Children were divided into four groups: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB.
Results
The prevalence of normal-weight children without central OB was 64.3% (796), normal weight with central OB 5% (66), OW/OB without central OB 11% (137), and OW/OB with central OB 21% (265). Normal weight with central OB had significantly higher triglycerides than normal-weight children without central OB (86 vs 70 mg/dL, respectively) and OW/OB children without central OB (81 vs 77 mg/dL). Multiple linear regression analyses showed that age, systolic BP, HDL-C, triglycerides, and maternal WC were significantly associated with children’s WC; R2 = 0.50 as well as children’s BMI; R2 = 0.37.
Conclusion
This study found that children with central OB might be at future higher cardiometabolic risk than those without central OB independently of the presence of OW/OB. However, future longitudinal studies should be performed to confirm these findings.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Institute of Medical Statistics and Informatics, Belgrade, Serbia
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University Children’s Clinic, Belgrade, Serbia
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University Children’s Clinic, Belgrade, Serbia
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Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia
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Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Objective
To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP).
Design
Single- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP.
Results
COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%).
Conclusion
The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.
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Objective
The aim of this study is to clarify, in girls with premature pubarche (PP), the influence of premature androgenization on the prevalence of polycystic ovary syndrome (PCOS).
Design and patients
Ninety-nine PP girls, 63 who developed PCOS and 36 who did not develop PCOS, were retrospectively included. Clinical, anthropometric, and metabolic parameters were evaluated at the time of diagnosis of PP and after 10 years from menarche to find predictive factors of PCOS.
Results
Young females with PP showed a PCOS prevalence of 64% and showed a higher prevalence of familial history of diabetes (P = 0.004) and a lower prevalence of underweight (P = 0.025) than PP-NO-PCOS. In addition, girls with PP-PCOS showed higher BMI (P < 0.001), waist circumference (P < 0.001), total testosterone (P = 0.026), visceral adiposity index (VAI) (P = 0.013), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), non-HDL cholesterol (P < 0.001) and lower age of menarche (P = 0.015), ISI-Matsuda (P < 0.001), DIo (P = 0.002), HDL cholesterol (P = 0.026) than PP-NO-PCOS. Multivariate analysis showed that WC (P = 0.049), ISI-Matsuda (P < 0.001), oral disposition index (DIo) (P < 0.001), VAI (P < 0.001), total testosterone (P < 0.001) and LDL-cholesterol (P < 0.001) are independent predictive factors for PCOS in girls with PP.
Conclusions
Our study established a strong association between multiple risk factors and development of PCOS in PP girls. These risk factors are predominantly related to the regulation of glucose, lipid, and androgen metabolism. Among these factors, WC, ISI-Matsuda, DIo, VAI, total testosterone, and LDL-cholesterol predict PCOS.
Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Objectives
We aimed to identify and characterize potential factors, both individually and jointly as a nomogram, associated with short stature and pre-shortness in Chinese preschool-aged children.
Methods
Total of 9501 children aged 3–6 years were recruited from 30 kindergartens in Beijing and Tangshan from September to December 2020 using a stratified random sampling method. Effect-size estimates are expressed as odds ratio (OR) and 95% CI.
Results
The prevalence of short stature and pre-shortness in preschool-aged children was 3.9% (n = 375) and 13.1% (n = 1616), respectively. Factors simultaneously associated with the significant risk for short stature, pre-shortness and both included BMI, paternal height, maternal height, birth weight, birth height, latter birth order (≥2) and less parental patience to children. Besides, breastfeeding duration (≥12 months) was exclusively associated with pre-shortness (OR, 95% CI, P: 1.16, 1.01 to 1.33, 0.037), and childhood obesity with both short stature (3.45, 2.62 to 4.54, <0.001) and short stature/pre-shortness (1.37, 1.15 to 1.64, <0.001). Modeling of significant factors in nomograms had descent prediction accuracies, with the C-index being 77.0, 70.1 and 71.2% for short stature, pre-shortness and both, respectively (all P < 0.001).
Conclusions
Our findings indicate the joint contribution of inherited characteristics, nutrition status from the uterus to childhood, and family psychological environment to short stature and pre-shortness in Chinese preschool-aged children. Further validation in other independent groups is warranted.
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St.Anna Kinderspital, Medical University of Vienna, Vienna, Austria
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Objective
Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry.
Design
The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included.
Methods
A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4.
Results
We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9–19.8) for patients <3 months (n = 329), 15.0 (14.6–15.3) for age ≥3–12 months (n = 463), 14.0 (13.7–14.3) for age 1–5.9 years (n = 745), 14.2 (14.0–14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6–15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg.
Conclusion
Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.
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Academic Centre for Growth, Erasmus University Medical Centre, Rotterdam, the Netherlands
Dutch Growth Research Foundation, Rotterdam, the Netherlands
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Diabeter, National Diabetes Care and Research Centre, Rotterdam, the Netherlands
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Department of Paediatric Endocrinology, Leiden University Medical Centre, Leiden, the Netherlands
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Academic Centre for Growth, Erasmus University Medical Centre, Rotterdam, the Netherlands
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Objective
Adolescents and young adults (AYA) with common endocrine disorders show a high dropout (up to 50%) after the transfer from paediatric to adult endocrinology. Little is known about transition readiness in rare endocrine conditions (rEC). This study aims to assess medical self-management skills (SMS) among AYA with rEC in relation to age and gender, in order to understand dropout and increase transition readiness.
Design
Cross-sectional study using web-based medical self-management questionnaires.
Methods
Questionnaires consisting of 54 questions in seven domains were filled out by the adolescents before the first shared appointment with both paediatric and adult endocrinologist.
Results
Fifty-seven patients (median age 17 years, 25/57 females) participated and generally scored well on most items. However, one out of seven did not know the name of their disorder, one sixth of the glucocorticoid users did not know that dose should be adapted in case of illness or surgery, over one-fifth had never ordered their repeat prescriptions themselves and two-thirds had never had a conversation alone with their doctor.
Conclusions
Several SMS among patients with rEC are insufficient, with regard to medical knowledge, practical skills and communication. As SMS are only weakly related to non-modifiable factors, such as age and gender, we recommend focussing on other factors to increase transition readiness. The timing, amount and ‘mode’ of medical information should be individualised. Transition checklists should be used to detect shortcomings in practical skills and communication, which can subsequently be trained with the help of parents, caregivers and/or e-technology.
Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain
Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Navarra Institute for Health Research (IdisNA), Pamplona, Spain
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Objective
The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.
Methods
Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- and 8-years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.
Results
There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (P < 0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89 and 82%, respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.
Conclusions
Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, reducing the need for GnRH stimulation testing.
