The Severity of Congenital Hypothyroidism With Gland-In-Situ Predicts Molecular Yield by Targeted Next-Generation Sequencing.

Introduction: Congenital hypothyroidism with gland-in-situ (CH-GIS) is usually attributed to mutations in the genes involved in thyroid hormone production. The diagnostic yield of targeted next-generation sequencing (NGS) varied widely between studies. We hypothesized that the molecular yield of targeted NGS would depend on the severity of CH.

Personalized Massive Open Online Course for Childhood Cancer Survivors: Behind the Scenes.

Background: Today, in France, it is estimated that 1 in 850 people aged between 20 and 45 years has been treated for childhood cancer, which equals 40,000 to 50,000 people. As late effects of the cancer and its treatment affect a large number of childhood cancer survivors (CCS) and only 30% of them benefit from an efficient long-term follow-up care for prevention, early detection, and treatment of late effects, health education of CCS represents a challenge of public health.

Objectives: Massive open online courses (MOOCs) are a recent innovative addition to the online learning landscape.

Mitotane (op'DDD) restores growth and puberty in nine children with Cushing's disease.

To investigate whether low-dose mitotane (up to 2 g/day) could be a temporary therapeutic alternative to transsphenoidal surgery (TSS) in pediatric Cushing's disease (CD). Twenty-eight patients with CD aged 12.2 years (± 2.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

Context: Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation.

Objective: This study aimed to investigate the role of potential modifiers of the dose response.

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy.

Pooled analysis of two case-control studies in New Caledonia and French Polynesia of body mass index and differentiated thyroid cancer: the importance of body surface area.

Background: New Caledonia and French Polynesia have among of the world highest thyroid cancer incidence rates. Studies have demonstrated a relationship between anthropometric parameters and the prevalence of cancer. In this study we evaluated further the relationship between body mass index (BMI) and other anthropometric parameters on the incidence of thyroid cancer in the New Caledonia and French Polynesia populations.

[The role of gonadal peptides in clinical investigation].

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement.

Gonadotrophic status in adolescents with pituitary stalk interruption syndrome.

Objective: Pituitary stalk interruption syndrome (PSIS) is a frequent cause of GH deficiency (GHD) and is commonly associated with other PH deficiencies (PHDs). Although previous reports have correlated multiple PHDs with severe anatomical lesions, the status of the gonadotrophic axis has not yet been thoroughly analysed.

Methods: We retrospectively reviewed the medical records of 27 patients (15 males, 12 females) with GHD and PSIS defined by MRI findings.

First reported case of intrachromosomal cryptic inv dup del Xp in a boy with developmental retardation.

We report here on a 6-year-old boy referred to the laboratory for karyotyping and SHOX microdeletion testing. The most significant clinical findings in this boy were small stature, Madelung deformity, facial dysmorphism, mild mental retardation and behavioral problems. R-, G- and RTBG-banding chromosome analysis showed a normal male karyotype.

[Prevention of child and adolescent vitamin D deficiency. II. Validation of a decision-making abacus based on sun exposure and vitamin D intakes].

Objectives: Rickets can still be observed among children and adolescents living in Europe, and a significant proportion of healthy children and adolescents presents serum 25-hydroxyvitamin D (25-(OH)D) values below the threshold indicating an insufficient vitamin D status. We have previously proposed detecting at risk individuals with a decision-making abacus based on questionnaires assessing calcium and vitamin D intakes and vitamin D production via sun exposure.

Methods: We tested the validity of this detection by receiver operating characteristic (ROC) analysis, using, as the main outcome measure, the serum 25-(OH)D values measured at the time of questionnaires presentation.

Aortic dilatation in Turner syndrome: the role of MRI in early recognition.

Background: Aortic dilatation and dissection are rare but important complications of Turner syndrome that increase the risk of sudden death in young patients.

Objective: To assess the value of aortic MRI in patients with Turner syndrome; in particular to demonstrate early aortic dilatation.

Materials And Methods: A total of 21 patients with Turner syndrome underwent MRI of the thoracic aorta with measurement of vessel diameter at four levels.

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.

[Neuroendocrine mechanisms of puberty onset].

An increase in pulsatile release of GnRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in GnRH release is still unclear. The GnRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state by central inhibition in the juvenile period.

Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.

Pseudotumor of the pituitary due to PROP-1 deletion.

Hypopituitarism associated with pituitary mass in childhood is most frequently the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient with an intrasellar pseudotumor associated with hypopituitarism, which led us to a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of the mass, diagnosis was revised.

Aetiological diagnosis of male sex ambiguity: a collaborative study.

Unlabelled: A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS).

PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.

Alterations of the gene encoding the pituitary transcription factor PROP1 were associated with congenital forms of multiple pituitary hormone deficiencies in several families. Among 23 patients with multiple pituitary hormone deficiencies screened for a PROP1 gene abnormality, nine belonging to eight unrelated families had homozygous PROP1 gene defects. All mutations were located in exon 2 and affected only two different sites: a homozygous AG deletion at codons 99/100/101 (n = 5); homozygous point mutations affecting codon 73: R73C (n = 2) or R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n = 1).

Prognosis of children with malignant pheochromocytoma. Report of 2 cases and review of the literature.

Malignant pheochromocytomas are rare in childhood and the prognosis of children with this tumor is not well known. We present 2 pediatric observations of malignant pelvic pheochromocytoma. Symptoms in both cases were headache and hypertension.

Lack of effect of GnRH agonists on final height in girls with advanced puberty: a randomized long-term pilot study.

GnRH agonists improve final height in girls with "true" precocious puberty. To test if a comparable effect can be obtained in older girls, we performed a long-term controlled study in 30 caucasian girls whose puberty started between 8.4 and 10 yr (9.

Clinical and prognostic aspects of adrenocortical neoplasms in childhood.

Background: A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy.

Procedures: Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model.

Results: Median age at diagnosis was 4 years.

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.

Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency.

Prop-1 is a newly isolated pituitary-specific paired-like homeodomain transcription factor whose cDNA sequence is well known in mouse. To study its involvement in human combined pituitary hormone deficiency (CPHD), we have isolated the human cDNA ortholog and determined the exon/intron organization and chromosomal localization of the human gene. A Prop-1 defect was characterized in three CPHD families.