Syndrome des ovaires polykystiques chez l’adolescente diabétique ou obèse [Polycystic ovary syndrome in obese or type 1 diabetic (T1D) adolescent girls]

Polycystic ovary syndrome (PCOS) is frequent during adolescence (prevalence ≈ 6 %), and the prevalence increases in obese or type 1 diabetic (T1D) adolescent girls. During puberty, PCOS diagnosis is difficult because of the overlap with some pubertal physiologic signs. The 2017 international consortium suggests two required diagnostic criteria: persistent menstrual disturbances and hyperandrogenism. PCOS physiopathology is complex, including interactions between genetic, epigenetic factors, primary ovarian abnormalities, neuroendocrine alterations, hormonal and metabolic factors. Insulin seems to have a central place in obese or T1D adolescent girls. The treatment is still debated and should be monitored according to the main symptoms

Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved.

Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients. In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations). We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039. Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care

A novel CHD7 mutation in an adolescent presenting with growth and pubertal delay.

Mutations in the CHD7 gene, encoding for the chromodomain helicase DNA-binding protein 7, are found in approximately 60% of individuals with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities and/or hearing loss). Herein, we present a clinical case of a 14-year-old male presenting for evaluation of poor growth and pubertal delay highlighting the diagnostic challenges of CHARGE syndrome. The patient was born full term and underwent surgery at 5 days of life for bilateral choanal atresia. Developmental milestones were normally achieved. At age 14 his height and weight were -2.04 and -1.74 standard deviation score respectively. He had anosmia as well as prepubertal testes and micropenis (4 cm×1 cm). The biological profile showed low basal serum testosterone and gonadotropins (testosterone, 0.2 nmol/L; luteinizing hormone, 0.5 U/L; follicle-stimulating hormone, 1.3 U/L), and otherwise normal pituitary function and normal imaging of the hypothalamic-pituitary area. The constellation of choanal atresia, anosmia, mild dysmorphic features, micropenis and delayed puberty were suggestive of CHARGE syndrome. Targeted genetic testing of CHD7 was performed revealing a de novo heterozygous CHD7 mutation (c.4234T>G [p.Tyr1412Asp]). Further paraclinical investigations confirmed CHARGE syndrome. Despite the presence of suggestive features, CHARGE syndrome remained undiagnosed in this patient until adolescence. Genetic testing helps clarify the phenotypic and genotypic spectrum to facilitate diagnosis, thus promoting optimal follow-up, treatment, and appropriate genetic counselling

Transcriptome, Methylome and Genomic Variations Analysis of Ectopic Thyroid Glands

Congenital hypothyroidism from thyroid dysgenesis (CHTD) is predominantly a sporadic disease characterized by defects in the differentiation, migration or growth of thyroid tissue. Of these defects, incomplete migration resulting in ectopic thyroid tissue is the most common (up to 80%). Germinal mutations in the thyroid-related transcription factors NKX2.1, FOXE1, PAX-8, and NKX2.5 have been identified in only 3% of patients with sporadic CHTD. Moreover, a survey of monozygotic twins yielded a discordance rate of 92%, suggesting that somatic events, genetic or epigenetic, probably play an important role in the etiology of CHTD.Journal ArticleResearch Support, Non-U.S. Gov'tValidation StudiesSCOPUS: ar.jinfo:eu-repo/semantics/publishe

A high prevalence of dual thyroid ectopy in congenital hypothyroidism: evidence for insufficient signaling gradients during embryonic thyroid migration or for the polyclonal nature of the thyroid gland?

BACKGROUND: Thyroid ectopy results from the failure of the thyroid precursor cells to migrate from the primordial pharynx to the anterior part of the neck. Most ectopic thyroids are revealed by congenital hypothyroidism and present as a single round mass at the base of the tongue, with no other thyroid tissue. However, some cases have dual ectopy, with part of the tissue having partially migrated. We hypothesized that this occurs more frequently than previously reported.¦METHODS: To determine the prevalence of dual ectopy, we reviewed the pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from thyroid ectopy diagnosed between 2002 and 2011 at our institution.¦RESULTS: We report a series of seven cases (9%) of dual ectopy, representing an incidence ranging from 1:50,000 to 1:70,000.¦CONCLUSIONS: Almost one in 10 cases with congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests that two populations of cells diverged at an early stage of development, which may arise from insufficient signaling gradients in surrounding tissues during early organogenesis or may indirectly support the polyclonal nature of the thyroid

Non-invasive assessment of coronary endothelial function in children and adolescents with type 1 diabetes mellitus using isometric handgrip exercise-MRI: A feasibility study.

Type 1 diabetes mellitus (T1DM) in children and adolescents is associated with significant cardiovascular morbidity and mortality. Early detection of vascular dysfunction is key to patient management yet current assessment techniques are invasive and not suitable for pediatric patient populations. A novel approach using isometric handgrip exercise during magnetic resonance imaging (IHE-MRI) has recently been developed to evaluate coronary endothelial function non-invasively in adults. This project aimed to assess endothelium-dependent coronary arterial response to IHE-MRI in children with T1DM and in age matched healthy controls. Healthy volunteers and children with T1DM (>5 years) were recruited. IHE-MRI cross-sectional coronary artery area measurements were recorded at rest and under stress. Carotid intima media thickness (CIMT) and aortic pulse wave velocity (PWV) were assessed for comparison. Student's t-tests were used to compare results between groups. Seven children with T1DM (3 female, median 14.8 years, mean 14.8 ± 1.9 years) and 16 healthy controls (7 female, median 14.8 years, mean 14.2 ± 2.4 years) participated. A significant increase in stress-induced cross-sectional coronary area was measured in controls (5.4 mm2 at rest to 6.39 mm2 under stress, 18.8 ± 10.7%, p = 0.0004). In contrast, mean area change in patients with T1DM was not significant (7.17 mm2 at rest to 7.59 mm2 under stress, 10.5% ± 28.1%, p = n.s.). There was no significant difference in the results for neither PWV nor CIMT between patients and controls, (5.3±1.5 m/s vs.4.8±0.7 m/s and 0.4±0.03mm vs.0.46 mm ± 0.03 respectively, both p = n.s.). Our pilot study demonstrates the feasibility of using a totally non-invasive IHE-MRI technique in children and adolescents with and without T1DM. Preliminary results suggest a blunted endothelium-dependent coronary vasomotor function in children with T1DM (>5 years). Better knowledge and new methodologies may improve surveillance and care for T1DM patients to reduce cardiovascular morbidity and mortality

Diabetes and immune thrombocytopenic purpura: a new association with good response to anti-CD20 therapy.

Type 1 diabetes (T1D) is rarely a component of primary immune dysregulation disorders. We report two cases in which T1D was associated with thrombocytopenia. The first patient, a 13-year-old boy, presented with immune thrombocytopenia (ITP), thyroiditis, and, 3 wk later, T1D. Because of severe thrombocytopenia resistant to immunoglobulins, high-dose steroids, and cyclosporine treatment, anti-cluster of differentiation (CD20) therapy was introduced, with consequent normalization of thrombocytes and weaning off of steroids. Three and 5 months after anti-CD20 therapy, levothyroxin and insulin therapy, respectively, were stopped. Ten months after stopping insulin treatment, normal C-peptide and hemoglobin A1c (HbA1c) levels and markedly reduced anti-glutamic acid decarboxylase (GAD) antibodies were measured. A second anti-CD20 trial for relapse of ITP was initiated 2 yr after the first trial. Anti-GAD antibody levels decreased again, but HbA1c stayed elevated and glucose monitoring showed elevated postprandial glycemia, demanding insulin therapy. To our knowledge, this is the first case in which insulin treatment could be interrupted for 28 months after anti-CD20 treatment. In patient two, thrombocytopenia followed a diagnosis of T1D 6 yr previously. Treatment with anti-CD20 led to normalization of thrombocytes, but no effect on T1D was observed. Concerning the origin of the boys' conditions, several primary immune dysregulation disorders were considered. Thrombocytopenia associated with T1D is unusual and could represent a new entity. The diabetes manifestation in patient one was probably triggered by corticosteroid treatment; regardless, anti-CD20 therapy appeared to be efficacious early in the course of T1D, but not long after the initial diagnosis of T1D, as shown for patient two

Natural history of growth hormone deficiency in a pediatric cohort.

BACKGROUND/AIMS: Controversies still exist regarding the evaluation of growth hormone deficiency (GHD) in childhood at the end of growth. The aim of this study was to describe the natural history of GHD in a pediatric cohort. METHODS: This is a retrospective study of a cohort of pediatric patients with GHD. Cases of acquired GHD were excluded. Univariate logistic regression was used to identify predictors of GHD persisting into adulthood. RESULTS: Among 63 identified patients, 47 (75%) had partial GHD at diagnosis, while 16 (25%) had complete GHD, including 5 with multiple pituitary hormone deficiencies. At final height, 50 patients underwent repeat stimulation testing; 28 (56%) recovered and 22 (44%) remained growth hormone (GH) deficient. Predictors of persisting GHD were: complete GHD at diagnosis (OR 10.1, 95% CI 2.4-42.1), pituitary stalk defect or ectopic pituitary gland on magnetic resonance imaging (OR 6.5, 95% CI 1.1-37.1), greater height gain during GH treatment (OR 1.8, 95% CI 1.0-3.3), and IGF-1 level <-2 standard deviation scores (SDS) following treatment cessation (OR 19.3, 95% CI 3.6-103.1). In the multivariate analysis, only IGF-1 level <-2 SDS (OR 13.3, 95% CI 2.3-77.3) and complete GHD (OR 6.3, 95% CI 1.2-32.8) were associated with the outcome. CONCLUSION: At final height, 56% of adolescents with GHD had recovered. Complete GHD at diagnosis, low IGF-1 levels following retesting, and pituitary malformation were strong predictors of persistence of GHD. © 2015 S. Karger AG, Basel