Background: An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Summary: The recommendations include the various neonatal screening approaches for CH as well as the etiology (also genetics), diagnostics, treatment, and prognosis of both primary and central CH. When CH is diagnosed, the expert panel recommends the immediate start of correctly dosed levothyroxine treatment and frequent follow-up including laboratory testing to keep thyroid hormone levels in their target ranges, timely assessment of the need to continue treatment, attention for neurodevelopment and neurosensory functions, and, if necessary, consulting other health professionals, and education of the child and family about CH. Harmonization of diagnostics, treatment, and follow-up will optimize patient outcomes. Lastly, all individuals with CH are entitled to a well-planned transition of care from pediatrics to adult medicine. Conclusions: This consensus guidelines update should be used to further optimize detection, diagnosis, treatment, and follow-up of children with all forms of CH in the light of the most recent evidence. It should be helpful in convincing health authorities of the benefits of neonatal screening for CH. Further epidemiological and experimental studies are needed to understand the increased incidence of this condition.

/pdf/congenital-hypothyroidism-a-2020-2021-consensus-guidelines-vyt2rew81x.pdf

Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update—An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology

Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.

/pdf/the-chinamap-analytics-of-deep-whole-genome-sequences-in-10-5attoicu6u.pdf

The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals.

In humans, the thyroid hormones T3 and T4 are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein thyroglobulin. The overall structure of thyroglobulin is conserved in all vertebrates. Upon thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T4 and T3 at distinct sites. T4 formation involves oxidative coupling between two DIT side chains, and de novo T3 formation involves coupling between an MIT donor and a DIT acceptor. Thyroid hormone synthesis is stimulated by TSH activating its receptor (TSHR), which upregulates the activity of many thyroid gene products involved in hormonogenesis. Additionally, TSH regulates post-translational changes in thyroglobulin that selectively enhance its capacity for T3 formation — this process is important in iodide deficiency and in Graves disease. 167 different mutations, many of which are newly discovered, are now known to exist in TG (encoding human thyroglobulin) that can lead to defective thyroid hormone synthesis, resulting in congenital hypothyroidism. T3 and T4 are synthesized in the thyroid gland in a process that involves the iodoglycoprotein thyroglobulin. In this Review, we consider the role of thyroglobulin in thyroid hormonogenesis from evolutionary, biochemical, molecular, cellular and physiological angles.

The role of thyroglobulin in thyroid hormonogenesis.

Congenital hypothyroidism (CH) may be primary, due to a defect affecting the thyroid gland itself, or central, due to impaired thyroid-stimulating hormone (TSH)-mediated stimulation of the thyroid gland as a result of hypothalamic or pituitary pathology. Primary CH is the most common neonatal endocrine disorder, traditionally subdivided into thyroid dysgenesis (TD), referring to a spectrum of thyroid developmental abnormalities, and dyshormonogenesis, where a defective molecular pathway for thyroid hormonogenesis results in failure of hormone production by a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in profound neurodevelopmental delay; therefore, CH is screened for in developed countries to facilitate prompt diagnosis. Central congenital hypothyroidism (CCH) is a rarer entity which may occur in isolation, or (more frequently) in association with additional pituitary hormone deficits. CCH is most commonly defined biochemically by failure of appropriate TSH elevation despite subnormal thyroid hormone levels and will therefore evade diagnosis in primary, TSH-based CH-screening programmes. This review will discuss recent genetic aetiological advances in CH and summarize epidemiological data and clinical diagnostic challenges, focussing on primary CH and isolated CCH.

/pdf/diagnosis-of-endocrine-disease-congenital-hypothyroidism-2glx24m523.pdf

DIAGNOSIS OF ENDOCRINE DISEASE: Congenital hypothyroidism: update and perspectives

Congenital hypothyroidism (CH), the most frequent form of preventable mental retardation, is predicted to have a relevant genetic origin. However, CH is frequently reported to be sporadic and candidate gene variations were found in <10% of the investigated patients. Here, we characterize the involvement of 11 candidate genes through a systematic Next Generation Sequencing (NGS) analysis. The NGS was performed in 177 unrelated CH patients (94 gland-in-situ; 83 dysgenesis) and in 3,538 control subjects. Non-synonymous or splicing rare variants (MAF < 0.01) were accepted, and their functional impact was predicted by a comprehensive bioinformatic approach and co-segregation studies. The frequency of variations in cases and controls was extended to 18 CH-unrelated genes. At least one rare variant was accepted in 103/177 patients. Monogenic recessive forms of the disease were found in five cases, but oligogenic involvement was detected in 39 patients. The 167 variations were found to affect all genes independently of the CH phenotype. These findings were replicated in an independent cohort of additional 145 CH cases. When compared to 3,538 controls, the CH population was significantly enriched with disrupting variants in the candidate genes (P = 5.5 × 10-7), but not with rare variations in CH-unrelated genes. Co-segregation studies of the hypothyroid phenotype with multiple gene variants in several pedigrees confirmed the potential oligogenic origin of CH. The systematic NGS approach reveals the frequent combination of rare variations in morphogenetic or functional candidate genes in CH patients independently of phenotype. The oligogenic origin represents a suitable explanation for the frequent sporadic CH occurrence.

A frequent oligogenic involvement in congenital hypothyroidism

This study made use of data generated by the UK10K Project and we acknowledge the contribution of the UK10K Consortium. This work was supported by Wellcome Trust Grants 100585/Z/12/Z (to N.S.), and 095564/Z/11/Z (to V.K.C.) and the National Institute for Health Research Cambridge Biomedical Research Center (to V.K.C., N.S.). E.G.S and C.A.A. are supported by the Wellcome Trust (098051). Funding for the UK10K Project was provided by the Wellcome Trust under award WT091310.

/pdf/comprehensive-screening-of-eight-known-causative-genes-in-4wcjsbtp9w.pdf

Comprehensive Screening of Eight Known Causative Genes in Congenital Hypothyroidism With Gland-in-Situ.

Investigating the genetic architecture of gland-in-situ congenital hypothyroidism by comprehensive screening of eight known causative genes

يبرعيلا فيس� ،يروبالخا ىس�ترم ،داوج مس�اه ،للها نافرع ،يدينس�لا لماس� نافلخ abstract: Objectives: Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI); however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. Methods: This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE). Results: The OI group had significantly lower peak early mitral valve flow velocity (P = 0.027), peak a-wave reversal in the pulmonary vein (P = 0.030) and peak early diastolic velocity of the mitral valve and upper septum (P = 0.001 each). The peak late diastolic velocities of the mitral valve (P = 0.002) and the upper septum (P = 0.037) were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve (P = 0.002) and upper septum (P = 0.001) were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Conclusion: Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI. مظعلا نوكت ض�رم نم نوناعي نيذلا ينغلابلا في ةيومدلا ةيعوألاو بلقلا في ةيفيظوو ةينيوكت تللاتخا دوجو ةيملعلا تاس�اردلا ترهظأا :فدهلا :ص�خللما دوجو ىدم نم ققحتلا لىإا ةس�اردلا هذه تفده :ةقيرطلا .لافطألا دنع ض�رلما اذهب ةقلعتلما تاس�اردلا في ض�قن كانه نأا لإا )OI( ض�قانلا في ةس�اردلا هذه تيرجأا :ةقيرطلا .ةبقارلما ةعوممج عم ةنراقلماب ض�رلما اذهب ينباس�لما لافطألا ىدل ةيومدلا ةيعوألاو بلقلا في تللاتخا ةينيوكتلا بلقلا ىدس� ةعس�أا تانايب ةنراقم تتم ثيح 2014 ض�طس�غأاو 2013 ويام ينب ،نامع ،طقس�م في ض�وباق ناطلس�لا ةعماج ىفس�تس�م ىس�رم نأا ةس�اردلا تنيب :جئاتنلا .ةميلس�لا ةبقارلما ةعوممج نم ةلاح 24 و ض�قانلا مظعلا نوكت ض�ربم ينباس�م ىس�رم 8 ينب ةيفيظولاو ةجوم ةورذو )P = 0.027( يجاتلا مامس�لل ركبلما قفدتلا ةعسر� ةورذل ةنراقلما ةعوممج نم يرثكب لقأا تاس�ايق مهيدل ض�قانلا مظعلا نوكت تناكو .)امهنم لكل P = 0.001( يولعلا زجالحاو يجاتلا مامس�لل ةركبلما ةيطاس�بنلا ةعسر�لا ةورذو )P = 0.030( يوئرلا ديرولا في عجاترلا مظعلا نوكت ىس�رم ةعوممج في يرثكب ىلعأا )P = 0.037( يولعلا زجالحاو )P = 0.002( يجاتلا مامس�لل ةرخأاتلما ةيطاس�بنلا ةعسر�لا ةورذ )P = 0.001( يولعلا زجالحاو )P = 0.002( يجاتلا مامس�لل ةرخأاتلما /ةركبلما ةيطاس�بنلا ةعسر�لا في ةورذلا ةبس�ن نإاف ،كلذ عمو ؛ض�قانلا نوكت ىس�رم ةعوممج في بركأا يوئرلا و رهبألا نايسر�لا راطقأاو سر�يألا ينطبلا داعبأا تناك اس�يأا .يرثكب ةنراقلما ةعوممج نم لقأا تناك .يعيبط لدعم تاذ ينقيرفلا لاكل ةيس�ابقنلا بلقلا ةفيظو نأا كلذك ةس�اردلا تنيبو .مس�لجا حطس� ةحاس�لم اهتس�رهف تم امدنع ض�قانلا مظعلا دجوت هنأا لإا يعيبط لدعم تاذ ض�قانلا مظعلا نوكت ض�ربم ينباس�لما لافطألا ىدل ةيس�ابقنلا بلقلا ةفيظو نأا ةس�اردلا تنيب :ةص�لالخا مجح برك كلذكو سر�يألا ينطبلا داعبأا ةدايز دوجو نع تنيب اهنأا امك .ةيطاس�بنلا بلقلا فئاظو في لي وأا للخ دوجوب يحوت ةطيس�ب تايرغت نوكت ض�ربم ينباس�لما راغس�لا ىس�رملل ةرمتس�لما ةعباتلماو ركبلما مييقتلا لىإا ةجالحا لىإا يرس�ت جئاتنلا هذه .ةيس�يئرلا ةيومدلا ةيعوألا .يفيظولا بلقلا ىدس� طيطختب ض�قانلا مظعلا

طيطتخ مادختساب ةيطاسبنلاا بلقلا ةفيظو في ركبم للاتخا دوجو ىلع ةلدأ صقانلا مظعلا نوكت ضربم ينباصلما لافطلأا دنع بلقلا

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Irfan Ullah

Author Tools

Chat about Author

Papers

Comprehensive Screening of Eight Known Causative Genes in Congenital Hypothyroidism With Gland-in-Situ.

Investigating the genetic architecture of gland-in-situ congenital hypothyroidism by comprehensive screening of eight known causative genes

طيطتخ مادختساب ةيطاسبنلاا بلقلا ةفيظو في ركبم للاتخا دوجو ىلع ةلدأ صقانلا مظعلا نوكت ضربم ينباصلما لافطلأا دنع بلقلا