Intellectual development in preschool children with early treated congenital hypothyroidism.
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ABSTRACT:
SUBMITTER: Seo MK
PROVIDER: S-EPMC5495975 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:Congenital hypothyroidism (CH) is one of the most common hereditary disorders affecting neonates worldwide. CH is a multifactorial complex disorder and can be caused by either environmental factors or genetic factors. We studied one Pakistani family with segregating mutations in CH inherited in an autosomal recessive manner. Using whole-exome sequencing (WES), we found a novel homozygous missense variant (c.2315A>G; p.Tyr772Cys) in the thyroid peroxidase (TPO) gene. Different bioinformatics prediction tools and Sanger sequencing were performed to verify the identified variant. Our findings highlight the importance of this gene in causing CH and mild-intellectual disability (ID) in two affected brothers. WES is a convenient and useful tool for the clinical diagnosis of CH and other associated disorders.
| S-EPMC7695822 | biostudies-literature
Project description:This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.
| S-EPMC6713841 | biostudies-other
Project description:PurposeProspective and longitudinal neuroimaging studies of posterior fossa tumors are scarce. Here we evaluate the early changes in white matter and intellectual outcome up to 3 years after diagnosis.Patients and methodsTwenty-two children with posterior fossa tumors and 24 similarly-aged healthy children participated. Patients included: (a) 12 individuals who received surgery, cranial-spinal radiation (CSR), and focal radiation to the tumor bed (CSR group) and (b) 10 individuals who received local therapy, either surgery only or surgery and focal radiation to the tumor bed (Local group). Diffusion tensor imaging (DTI) and intelligence measures were obtained an average of 3 months after diagnosis and then at 12, 24, and 36 months later. DTI tractography and voxel-wise approaches were employed. The Neurological Predictor Scale was used to summarize the type and amount of treatment for PF tumor patients. Linear mixed modelling was used to evaluate group differences at baseline and changes over time in DTI metrics for both the specific white matter tracts and voxel-wise, as well as for intelligence measures.ResultsBased on tractography, patients treated with CSR had significantly higher Axial and Mean diffusivity in the cortical-spinal tracts (CST) 3 month after diagnosis - particularly on the right side, p < .003, compared to healthy children. Mean diffusivity in right CST decreased over time in this group of patients, p = .001. No differences compared to controls were evident in specific tracts for the Local group, p > .10. Voxel-wise analyses revealed multiple areas of white matter compromise in both patients groups. Notably, both patient groups had lower scores on intelligence measures compared to the Control group: The CSR group displayed lower performance 3 months following diagnosis, ps < 0.001, and their performance remained stable over time ps > 0.10, whereas the Local group displayed no differences at 3 months, ps> 0.10, but their performance declined over time, ps < 0.01. At baseline, higher MD in right CST predicted lower Perceptual Reasoning scores across all participants, p = .001. Furthermore, lower FA in left IFOF at baseline predicted decline in Processing Speed over time, p = .001. In patients, more aggressive treatment protocols and presence of mutism were related to lower performance on intelligence measures at baseline, ps < 0.04.ConclusionsChildren treated with CSR displayed diffuse white matter compromise and poor intellectual outcome shortly after radiation treatment. There was evidence of subsequent growth of white matter structure, but stable intellectual insult. Conversely, in children treated with either surgery only or surgery and focal radiation to the tumor bed we observed less compromise of white matter early following treatment and no intellectual insult compared to healthy children. However, declines in intellectual function were evident for these children, though their performance remained within the average normative range. Overall, results suggest that early intervention is necessary to circumvent these deficits.
| S-EPMC6139996 | biostudies-literature
Project description:Congenital hypothyroidism (CH) is the most common cause of preventable mental retardation. Recently, the detection of CH cases with eutopic thyroid gland has increased due to neonatal screening programs. In this study, we aimed to identify and evaluate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid gland.We retrospectively reviewed 100 children diagnosed with CH and with eutopic thyroid gland. All subjects were treated with levothyroxine and underwent re-evaluation after 3 years of age.Of the 100 CH patients, 35 (35.0%) were diagnosed with permanent CH (PCH) and 65 (65.0%) were diagnosed with transient CH (TCH). The initial thyroid stimulating hormone levels were significantly lower in the TCH subjects than in PCH subjects. In addition, the mean doses of levothyroxine (µg/kg/day) at the 1st, 2nd, and 3rd year of treatment were significantly lower in subjects with TCH than in PCH subjects with eutopic thyroid gland. Based on the receiver operating characteristic (ROC) curve, the optimal cutoff dose of levothyroxine at 3 years of 2.76 µg/kg/day could predict TCH, and was associated with 87.3% sensitivity and 67.6% specificity, with an area under the ROC curve of 0.769.The levothyroxine dose requirement during treatment period has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid gland.
| S-EPMC5495977 | biostudies-other
Project description:Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA). Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA. Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
| S-EPMC9048185 | biostudies-literature
Project description:BackgroundChildren with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established.MethodsChildren with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded.ResultsFifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems.ConclusionsChildren with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.ImpactPreschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.
| S-EPMC10227180 | biostudies-literature
Project description:Congenital hypothyroidism (CH) is due to dyshormonogenesis in 10% to 15% of subjects worldwide but accounts for 60% of CH cases in the Sudan. To investigate the molecular basis of CH in Sudanese families. Clinical phenotype reporting and serum thyroid hormone measurements. Deoxyribonucelic acid extraction for whole-exome sequencing and Sanger sequencing. University research center. Twenty-six Sudanese families with CH. Clinical evaluation, thyroid function tests, genetic sequencing, and analysis. Our samples and information regarding samples from the literature were used to compare TG (thyroglobulin) and TPO (thyroid peroxidase) mutation rates in the Sudanese population with all populations. Mutations were found in dual-oxidase 1 (DUOX1), dual-oxidase 2 (DUOX2), iodotyrosine deiodinase (IYD), solute-carrier (SLC) 26A4, SLC26A7, SLC5A5, TG, and TPO genes. The molecular basis of the CH in 7 families remains unknown. TG mutations were significantly higher on average in the Sudanese population compared with the average number of TG mutations in other populations (P < 0.05). All described mutations occur in domains important for protein structure and function, predicting the CH phenotype. Genotype prediction based on phenotype includes low or undetectable thyroglobulin levels for TG gene mutations and markedly higher thyroglobulin levels for TPO mutations. The reasons for higher incidence of TG gene mutations include gene length and possible positive genetic selection due to endemic iodine deficiency.
| S-EPMC7093074 | biostudies-literature
Project description:OBJECTIVE: Congenital hypothyroidism is characterized by inadequate thyroid hormone production in newborn infants. Many infants with CH have co-occurring congenital malformations. This is an investigation on the frequency and types of congenital anomalies in infants with congenital hypothyroidism born from May 2006-2010 in Hamadan, west province of Iran. METHODS: The Iranian neonatal screening program for congenital hypothyroidism was initiated in May 2005. This prospective descriptive study was conducted in infants diagnosed with congenital hypothyroidism being followed up in Pediatric Endocrinology Clinic of Besat Hospital, a tertiary care centre in Hamadan. Cases included all infants with congenital hypothyroidism diagnosed through newborn screening program or detected clinically. Anomalies were identified by clinical examination, echocardiography, and X-ray of the hip during the infant's first year of life. RESULTS: A total of 150 infants with biochemically confirmed primary congenital hypothyroidism (72 females and 78 males) were recruited during the period between May 2006-2010. Overall, 30 (20%) infants had associated congenital anomalies. The most common type of anomaly was Down syndrome. Seven infants (3.1%) had congenital cardiac anomalies such as: ASD (n=3), VSD (n=2), PS (n =1), PDA (n=1). Three children (2.6%) had developmental dysplasia of the hip (n=3). CONCLUSION: The overall frequency of Down syndrome, cardiac malformation and other birth defect was high in infants with CH. This reinforces the need to examine all infants with congenital hypothyroidism for the presence of associated congenital anomalies.
| S-EPMC3472568 | biostudies-other
Project description:BACKGROUND:Congenital hypothyroidism (CH) is one of the most common endocrine diseases in childhood. A significant proportion of CH cases are transient, but the risk factors for permanent CH (PCH) are not yet well established. The current guidelines suggest using levothyroxine until the age of 3?years, but some studies suggest the possibility of earlier discontinuation. However, few, if any, studies have followed up on the results of early discontinuation. This study aimed to identify predictive factors of transient CH among infants with CH. We also investigated the results in patients who underwent a trial of early discontinuation. METHODS:We gathered data regarding infants diagnosed with CH between July 2005 and July 2015 by retrospective chart review. Those with aplastic, hypoplastic or ectopic glands on thyroid ultrasonography or scan were excluded. Among them, early discontinuation subgroup was defined as those who discontinued levothyroxine before 30?months of age. RESULTS:From the 80 infants (40 males, 40 females) enrolled in this study, 51 were preterm. Nine (11.3%) were diagnosed with PCH. Compared with transient cases, those with PCH were on higher levothyroxine dose at discontinuation (4.3 vs 2.9??g/kg, P?<?0.001). There was no difference in the proportion of permanent cases between preterm and full-term groups. In preterm group,infants with PCH required higher levothyroxine dose at discontinuation than those with transient CH (3.8 vs 2.5??g/kg, P?=?0.018). Levothyroxine discontinuation at a dose of 2.86??g/kg could suggest PCH (sensitivity, 88.9%; specificity, 71.0%). Among the 9 patients who underwent a trial of early discontinuation, 8 successfully discontinued levothyroxine. CONCLUSION:The majority of CH patients discontinued levothyroxine successfully, including those who underwent a trial of early discontinuation. Higher levothyroxine dose at the time of discontinuation was found to be a predictive factor for PCH.
| S-EPMC6873549 | biostudies-literature
Project description:Eighty-five percent of the studies of patients with congenital hypothyroidism (CH) treated with Levothyroxine (L-T4) report neuropsychological sequelae throughout life. In neonates and infants, there is a deficit in sensorimotor skills (impaired balance). In preschool and elementary school children and adolescents, there are alterations in intellectual quotient (low scores), language (delayed phonological acquisition), memory (visual, verbal, visuospatial, visuoconstructive, autobiographical, and semantic), sensorimotor skills (impaired fine and gross motor control), and visuoconstructive-visuospatial domain (low scores in spatial location, block design, and object assembly). These neuropsychological domains are also affected in young adults, except for language (adequate verbal fluency) and visuoconstructive-visuospatial domain (no data). The onset and severity of neuropsychological sequelae in patients with treated CH depend on several factors: extrinsic, related to L-T4 treatment and social aspects, and intrinsic, such as severity and etiology of CH, as well as structural and physiological changes in the brain. In this review, we hypothesized that thyroid hormone hyposensitivity (THH) could also contribute to neuropsychological alterations by reducing the effectiveness of L-T4 treatment in the brain. Thus, further research could approach the THH hypothesis at basic and clinical levels to implement new endocrinological and neuropsychological therapies for CH patients.
| S-EPMC9224966 | biostudies-literature