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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While subclinical or overt hypothyroidism are common in Down syndrome (DS); Graves’ disease (GD) is rare (ranges 0.6–3%). We aimed to evaluate the clinical features, course, and treatment of GD in children with DS and compare them with those without DS. Among 161 children with GD, 13 (8 female, 5 male) had DS (8%). Data were collected retrospectively from patients’ medical records. The mean age at diagnosis was 10.6 ± 4.5 years, with a female-to-male ratio 1.6:1. The main symptoms were weight loss (n = 6), increased irritability (n = 3), and increased sweating (n = 3). None had orbitopathy. Seven of 11 patients with a thyroid ultrasound at diagnosis had a goitre. On admission, all had thyroid-stimulating hormone (TSH) <0.01 mU/L (normal range (NR): 0.51–4.30), free triiodothyronine, free thyroxine (mean ± s.d .), and thyrotrophin receptor antibodies (median, range) were 22.2 ± 10.2 pmol/L (NR: 3.5–8.1), 50.2 ± 18.7 pmol/L (NR 12.6–20.9), and 17.0 (2.89–159.0) U/L (NR <1), respectively. Patients were treated either with methimazole (n = 10) or carbimazole (n = 3), a dose of 0.54 ± 0.36 mg/kg/day. The treatment was ‘block and replace’ in ten patients and ‘dose titration’ in three patients, with a mean duration of 43.4 ± 11.0 months. Of 13 patients, four are still receiving primary treatment, three are in remission, one patient had two medically treated recurrences, three underwent surgery without complications, and two patients were lost to follow-up. Our data show that the clinical course of GD in patients with DS was similar to those without DS and suggest that a prolonged medical therapy should be the preferred option.
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
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INSERM UMR_S933, Paris, France
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France
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Human 3 beta-hydroxysteroid dehydrogenase deficiency (3b-HSD) is a very rare form of congenital adrenal hyperplasia resulting from HSD3B2 gene mutations. The estimated prevalence is less than 1/1,000,000 at birth. It leads to steroidogenesis impairment in both adrenals and gonads. Few data are available concerning adult testicular function in such patients. We had the opportunity to study gonadal axis and testicular function in a 46,XY adult patient, carrying a HSD3B2 mutation. He presented at birth a neonatal salt-wasting syndrome. He had a micropenis, a perineal hypospadias and two intrascrotal testes. HSD3B2 gene sequencing revealed a 687del27 homozygous mutation. The patient achieved normal puberty at the age of 15 years. Transition from the paediatric department occurred at the age of 19 years. His hormonal profile under hydrocortisone and fludrocortisone treatments revealed normal serum levels of 17OH-pregnenolone, as well as SDHEA, ACTH, total testosterone, inhibin B and AMH. Pelvic ultrasound identified two scrotal testes of 21 mL each, without any testicular adrenal rest tumours. His adult spermatic characteristics were normal, according to WHO 2010 criteria, with a sperm concentration of 57.6 million/mL (N > 15), 21% of typical forms (N > 4%). Sperm vitality was subnormal (41%; N > 58%). This patient, in contrast to previous reports, presents subnormal sperm parameters and therefore potential male fertility in a 24-years-old patient with severe 3b-HSD deficiency. This case should improve counselling about fertility of male patients carrying HSD3B2 mutation.
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Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester, UK
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Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester, UK
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Background
Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c.
Aims
(1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c.
Methods
Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2–10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded.
Results
Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = −0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328) or at 1 year (t = −1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level.
Conclusion
We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.
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-ERN is supported by the European Societies of Adult and Paediatric Endocrinology. It brings together the expertise of 71 centres from 19 countries in the field of rare endocrine diseases ( https://endo-ern.eu ). This review aims to inform about possible
Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
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Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
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Centre for Endocrinology, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, London, UK
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Department of Endocrinology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
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Department of Paediatric Endocrinology, Makarios Children's Hospital, Nicosia, Cyprus
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Sussex Community NHS Trust, Brighton, UK
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Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
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The University of Dublin, Trinity College Dublin, Dublin, Republic of Ireland
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, usually every 6 months, similar to British Society for Paediatric Endocrinology and Diabetes (BSPED) guidelines ( 121 ). Where transdermal testosterone is not available, low doses of injectable depot testosterone can be considered. When there is pubertal
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ready by early 2019 and included endorsement of links to the e-learning resources of both learned societies: the European Society of Endocrinology’s e-learning platform and European Society for Paediatric Endocrinology’s e-learning portal ( https
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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 Paediatrics, 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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(related to the chronic endocrine disorder) in the 2 years after transfer to AC. Inclusion criteria We included patients who were treated at Erasmus MC-Sophia department of Paediatric Endocrinology between 1 January 2013 and 31 December 2014, who
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Background
Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism caused by an activating GLUD1 mutation.
Objective
The aim of this study was to determine the clinical profile and long-term neurological outcomes in children with HI/HA syndrome.
Method
This study is a retrospective review of patients with GLUD1 mutation, treated at two centers in the UK and Russia, over a 15-year period. Different risk factors for neuro-developmental disorders were analysed by Mann–Whitney U test and Fisher’s exact P test.
Results
We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 h–18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. Twenty four cases responded to diazoxide and protein restriction whilst one patient underwent partial pancreatectomy. In total, 13 cases (52%) developed neurodevelopmental manifestations. Epilepsy (n = 9/25, 36%), learning difficulties (n = 8/25, 32%) and speech delay (n = 8/25, 32%) were the most common neurological manifestation. Median age of presentation for epilepsy was 12 months with generalised tonic-clonic seizures being the most common (n = 4/9, 44.4%) followed by absence seizures (n = 3/9, 33.3%). Early age of presentation (P = 0.02), diazoxide dose (P = 0.04) and a mutation in exon 11 or 12 (P = 0.01) were associated with neurological disorder.
Conclusion
HI/HA syndrome is associated with wide spectrum of neurological disorders. These neurological manifestations were more frequent in cases with mutations affecting the GTP-binding site of GLUD1 in our cohort.
Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK
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Department of Paediatric Endocrinology, Ghent University Hospital, Ghent, Belgium
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Department of Medicine & Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands
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Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, the Netherlands
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Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
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platform was disseminated through allied professional societies including the European Society of Endocrinology (ESE) and the European Society for Paediatric Endocrinology (ESPE), with the platform open to all centres that look after people with such
