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1.
J Clin Endocrinol Metab ; 108(9): e779-e788, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36884306

RESUMO

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. METHODS: Targeted NGS was performed in 103 CH-GIS patients from the French national screening program referred to the Reference Center for Rare Thyroid Diseases of Angers University Hospital. The custom targeted NGS panel contained 48 genes. Cases were classified as solved or probably solved depending on the known inheritance of the gene, the classification of the variants according to the American College of Medical Genetics and Genomics, the familial segregation, and published functional studies. Thyroid-stimulating hormone at CH screening and at diagnosis (TSHsc and TSHdg) and free T4 at diagnosis (FT4dg) were recorded. RESULTS: NGS identified 95 variants in 10 genes in 73 of the 103 patients, resulting in 25 solved cases and 18 probably solved cases. They were mainly due to mutations in the TG (n = 20) and TPO (n = 15) genes. The molecular yield was, respectively, 73% and 25% if TSHsc was ≥ and < 80 mUI/L, 60% and 30% if TSHdg was ≥ and < 100 mUI/L, and 69% and 29% if FT4dg was ≤ and > 5 pmol/L. CONCLUSION: NGS in patients with CH-GIS in France found a molecular explanation in 42% of the cases, increasing to 70% when TSHsc was ≥ 80 mUI/L or FT4dg was ≤ 5 pmol/L.


Assuntos
Hipotireoidismo Congênito , Humanos , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Mutação , Genômica , Sequenciamento de Nucleotídeos em Larga Escala
2.
Ann Endocrinol (Paris) ; 78(2): 98-103, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28483364

RESUMO

The diagnostic approach to tall stature in children is based on collecting birth data (macrosomia), sizes and family puberty, a family history of constitutional or pathological tall stature, search for a delay of development, dysmorphia, disproportion, analysis of the growth velocity (normal or accelerated), general examination and assessment of puberty, and bone age. When there is a history of psychomotor retardation, a family history of pathological tall stature, or a disproportion in the clinical examination, the genetic causes of tall stature will be mentioned. The most frequent causes are Marfan syndrome and similar, Sotos syndrome, Beckwith-Wiedemann syndrome, Klinefelter syndrome, and MEN2B. There are many genetic syndromes with tall stature, justifying consultation with the geneticist. When the speed of growth is accelerated, first of all it evokes puberty and early pseudopuberty, obesity and acromegaly. Finally, when the growth velocity is regular, and the parents are of tall stature, it evokes constitutional tall stature: this is the most frequent diagnosis, to retain after having rejected pathological tall statures.


Assuntos
Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/terapia , Acromegalia/diagnóstico , Acromegalia/terapia , Estatura , Criança , Gigantismo/diagnóstico , Gigantismo/terapia , Crescimento , Humanos
3.
Ann Endocrinol (Paris) ; 78(5): 462-468, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28870706

RESUMO

Severe obesity (body mass index>120% of BMI IOTF-30 cut off) and morbid obesity (BMI>140% of BMI IOTF-30 cut off) affect 5 to 10% of obese adolescents in France. Organic complications can be found in about 50% of these patients, and depressive symptoms in one-third of them. Finally, over 70% will suffer from adult morbid obesity associated with a marked increase in morbidity and mortality. However, the reversion of obesity strongly decreases, and may even cancels, these risks. In controlled randomized studies, lifestyle interventions have limited effectiveness on BMI in children (and none in adolescents). Bariatric surgery has been shown to have short-term effectiveness in adolescents with severe and morbid obesity: the average BMI loss after gastric banding was 11.6kg/m2 (95% confidence interval from 9.8 to 13.4), 16.6kg/m2 (95% confidence interval from 13.4 to 19.8) after bypass, and 14.1kg/m2 (95% confidence interval 10.8 to 17.5) after sleeve gastrectomy. The resolution of comorbidities was the main aim, as well as the improvement of quality of life. This is not a simple surgical intervention, and minor side effects have been reported in approximately 10-15% of teenagers who underwent surgery (more common with the gastric band), and severe side effects in nearly 1-5% (mainly with bypass). In France, recommendations regarding indications, the care pathway, multidisciplinary meetings, reference management structures and postoperative care have been published by the French National Health Authority (HAS) in 2016 to provide a framework for bariatric surgery in underage patients.


Assuntos
Adolescente , Cirurgia Bariátrica/tendências , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Cirurgia Bariátrica/psicologia , Cirurgia Bariátrica/normas , França , Humanos , Obesidade/psicologia , Qualidade de Vida , Resultado do Tratamento
4.
Horm Res Paediatr ; 83(2): 111-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25591844

RESUMO

UNLABELLED: Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide-binding protein α-subunit) mutation (PHP1A) or epimutation (PHP1B). To determine the presence of hypothyroidism at birth we conducted a retrospective study in our cohort of patients presenting with either PHP1A (n = 116) or PHP1B (n = 99). We also investigated patients presenting at birth with congenital hypothyroidism (CH) and a eutopic thyroid gland for phosphocalcium abnormalities suggesting PTH resistance and PHP. Our study reveals CH as the earliest diagnostic clue for PHP1A, but not for PHP1B. We estimated the frequency of CH at birth to be between 8 and 34% in patients presenting with PHP1A. The elevation of phosphatemia and PTH concentration precedes hypocalcemia in PHP1A. Conversely, the frequency of PHP1A in patients presenting CH is dramatically low. This may be due to the low prevalence of PHP1A which remains unknown. CONCLUSIONS: Subclinical and overt hypothyroidism can occur in PHP1A patients at birth many years before PTH resistance becomes clinically apparent. Although such cases appear to be rare, some pediatric patients with unexplained CH are likely to benefit from measuring calcium, phosphorus, and PTH for extended periods of time.


Assuntos
Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/terapia , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Gêmeos Monozigóticos , Criança , Pré-Escolar , Cromograninas , Hipotireoidismo Congênito/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Lactente , Masculino , Mutação , Pseudo-Hipoparatireoidismo/genética
5.
J Clin Endocrinol Metab ; 100(8): 2972-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26020629

RESUMO

CONTEXT: Intrauterine programming of the somatotropic axis has been hypothesized in cases of intrauterine growth retardation. OBJECTIVE: The objective of the study was to study the effects of birth weight and body composition on GH sensitivity. DESIGN: This was a cross-sectional study with a single GH administration to assess GH sensitivity. SETTING: The study was conducted at the Department of Pediatric Endocrinology of an academic medical center. PATIENTS: One hundred normal short children aged from 4 to 17 years old (44 girls, 56 boys) separated into four groups: early childhood (aged 4-8 y, n = 14), late childhood (aged 9-12 y, pubertal stage 1, n = 30), early puberty (aged 10-15 y, stage 2, n = 32), and midpuberty (aged 12-17 y, stages 3 and 4, n = 24). INTERVENTION AND MAIN OUTCOME MEASURE: Serum IGF-1 at baseline and 24 hours after a single administration of GH (2 mg/m(2)) were measured. RESULTS: δIGF-1 significantly increased across the groups (P < .0001) with no gender difference, whereas the percentage of change in IGF-1 was similar (47% ± 32%). Independent predictors of δIGF-1 were birth weight SD score, fat percentage, fasting insulin (all positive predictors), and free fatty acids (negative predictor), with age, puberty, and baseline IGF-1 as adjusting variables (multiple R = 0.73, P < .0001). Independent predictors of the percentage of change in IGF-1 were birth weight SD score, fat percentage, and baseline IGF-1 (multiple R = 0.43, P < .001). CONCLUSION: This study suggests that in cases of low birth weight, intrauterine programming of GH sensitivity may be an adaptation to an expected poor postnatal nutritional environment, serving to restrict the anabolic action of GH. Conversely, postnatal excess energy stores may promote the anabolic action of GH.


Assuntos
Peso ao Nascer/fisiologia , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Adolescente , Glicemia/metabolismo , Composição Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Estudos Transversais , Desenvolvimento Embrionário/fisiologia , Feminino , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Insulina/metabolismo , Masculino
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