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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hirschsprung's disease is marked by constipation from the time of birth, with the development, if uncorrected, of a protuberant abdomen and flared costal margins. The rectal ampulla is empty and the abdomen is filled with fecal masses. Pain is not prominent. Flatus is passed in large amounts. Encopresis does not occur. Barium enema shows the characteristic narrowed distal rectal segment and biopsy of the rectum shows absence of the ganglion cells of the myenteric plexus. Treatment is operative resection of the distal narrow segment and a primary anastomosis.Hirschsprung's disease may be mimicked in children with:1. Psychogenic constipation-pseudo-Hirschsprung's disease. Unlike Hirschsprung's disease, symptoms do not appear at birth, encopresis is common, and the barium enema shows no narrow distal segment.2. Mental retardation and cerebral defect.3. Corrected imperforate anus-on the basis of stenosis, imperfect innervation or poor habit training.4. Cretinism-with severe constipation and intestinal dilatation perhaps the presenting symptoms. Treatment of these four groups of children with severe constipation not due to Hirschsprung's disease is:For Group 1, open discussion with parent and child. Assumption by the physician of full control of the details of treatment, and relegation of parent to the role of the physician's agent in following the prescribed regimen. For Group 2, an enema regimen. Whereas fairly rapid restoration (and then persistence) of normal bowel habit can be expected in Group 1, the basic defects in Group 2 may require indefinite continuation of treatment. For Group 3, regular enema regimen, in the less severe cases-one identical with that used in Group 1, and dilatation of strictures or anoplasty. In Group 4, thyroid hormone therapy relieves the constipation of hypothyroidism and causes reversion of radiographic changes in the colon and rectum.
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PMID:Hirshsprung's disease; the clinical differentiation and treatment of children with Hirschsprung's disease and pseudo-Hirschsprung's disease. 1356 Nov 8

A lack of thyroid hormone in the postnatal period causes an irreversible mental retardation, characterized by a slowing of thoughts and movements accompanied by prolonged latencies of several evoked potentials and slowed electroencephalographic rhythms. Here we show that in cultured hippocampal and cortical neurons from postnatal rats treatment with thyroid hormone not only up-regulates Na(+)-current densities but also increases rates of rise, amplitudes and firing frequencies of action potentials. Furthermore, we show that the regulation of the Na(+)-current density by thyroid hormones also occurs in vivo: recordings from acutely isolated cortical neurons obtained from hypothyroid, euthyroid and hyperthyroid postnatal rats showed that hypothyroidism decreases the ratio of Na(+) inward- to K(+) outward-currents while hyperthyroidism upregulates Na(+)-currents with respect to K(+)-currents. Our observation of a regulation of neuronal excitability by thyroid hormone offers a direct explanation for the origin of various neurological symptoms related to thyroid dysfunction.
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PMID:Thyroid hormone regulates excitability in central neurons from postnatal rats. 1506 80

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.
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PMID:Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. 1550 May 40

Resistance to thyroid hormone (RTH) is a syndrome of reduced sensitivity to thyroid hormone, most commonly caused by mutations in the thyroid hormone receptor (TR) beta gene. Mutations are mostly located in the ligand-binding domain of the TRbeta, decreasing T(3) binding to the mutant TRbeta molecule, which in turn interferes with the function of the wild-type (WT) TR. A total of 122 different TRbeta gene mutations have been identified so far, with 46 occurring in more than one family. We now report a family with two novel TRbeta mutations occurring in the same nucleotide. The proposita had two children from each of her two marriages. One daughter and one son from each marriage had severe RTH with free T(4) and T(3) levels 3- to 4-fold the mean normal values and unsuppressed TSH, mental retardation, and deafness. The proposita had a missense mutation (GTG to GGG) in codon 458 of the TRbeta gene, resulting in the replacement of the normal valine with glycine (V458G). Although this mutation was transmitted to her affected son, the mutated codon in her affected daughter was GAG, encoding glutamic acid (V458E). Haplotype analysis showed that this de novo mutation occurred on the already mutant allele of the proposita. Cotransfection of each of these mutant TRbetas with the wild-type TRbeta showed a potent dominant negative effect. Large amounts of T(3) were required to dissociate homodimers of the mutant TRbeta bound to DNA. In addition, and in contrast to other mutant TRbetas with severe T(3)-binding defects, homodimer release failed to recruit the steroid receptor coactivator. No defects in heterodimerization with retinoid X receptor-alpha or association with a nuclear receptor corepressor, were identified. These in vitro data are in agreement with the in vivo phenotype of severe RTH. Unique and previously unreported in human inherited diseases is the occurrence of a de novo mutation at an already mutant nucleotide. Because the occurrence by chance is extremely unlikely, it is postulated that the presence of three guanines in the sequence created by the mutant nucleotide of the proposita results in a mutagenic site prone to de novo mutation.
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PMID:A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone. 1559 85

The mechanism by which a lack of thyroid hormone in the early development of the brain causes permanent mental retardation in cretins is currently unknown. On the other hand, an abnormality in dopamine-related brain function is believed to underlie some forms of mental illness. In this study, we demonstrate that although the activation of a dopaminergic D(2)-like receptor inhibited glutamatergic transmission in the hippocampal slices of normal adult rats, indicating the inhibitory action of the D(2)-like receptor on glutamatergic transmission, it markedly enhanced glutamatergic transmission both in a mutant hypothyroid rat with a missense mutation in thyroglobulin and in hypothyroid rats treated with methylmercaptoimidazole (MMI), indicating the excitatory action of the D(2)-like receptor on glutamatergic transmission. Paired pulse facilitation of field excitatory postsynaptic potentials was reduced by the activation of the D(2)-like receptors from MMI-induced hypothyroid rats, suggesting a presynaptic locus of the excitatory action of the D(2)-like receptors. In normal rats, the excitatory D(2)-like dopamine receptors were observed in the developing stages and were completely replaced by normal inhibitory responses up to adulthood. Furthermore, the continuous supplement of thyroxine from birth exerted a normalising effect on the abnormal excitatory property of D(2)-like dopamine receptors in the hippocampal slices of MMI-treated hypothyroid rats. From these results, it is suggested that thyroxine may play a crucial role in reversing the excitatory property of D(2)-like dopaminergic receptors in the immature brain to an inhibitory one in the mature brain. Moreover, we suggest that the abnormal excitatory property of D(2)-like dopaminergic receptors may develop in response to a lack of thyroxine and may contribute to some central nervous system deficits, including cognitive dysfunctions accompanied by hypothyroidism.
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PMID:Dopamine D(2)-like receptor function is converted from excitatory to inhibitory by thyroxine in the developmental hippocampus. 1628 31

Genetic defects attributable to the genes involved in the hypothalamus-pituitary-thyroid (HPT) gland axis can cause abnormal thyroid hormone function and mental retardation (MR). Pit-1, encoded by the POU1F1 gene on human chromosome 3p11, is a pituitary-specific transcription factor responsible for the expression of several pituitary hormones. Thyrotropin is one of these hormones and is an important regulator in the HPT axis. One of the symptoms of patients with POU1F1 mutations is hypothyroidism and abnormalities of the nervous system early in the period after birth. We performed a case-control association study and a quantitative analysis of IQ to investigate the possible genetic contribution of POU1F1 in the Chinese Han population. Pairwise linkage disequilibrium (LD) analysis showed that rs300996, snp-7057 and rs300977 were in strong LD. There were significant differences of allele, genotype and haplotype frequencies of these three single nucleotide polymorphisms (SNPs) between cases and controls. When we conducted a breakdown comparison between cases and controls within different gender groups, no positive results in males were found. In females, however, we found significant differences between cases and controls in allele frequency distribution of rs300996 (P=0.0003), snp-7057 (P=0.0001) and rs300977 (P=0.0005) and in the distributions of common haplotypes combined by these SNPs (global P=0.0050). The P-value was 0.0301 for rs300996 and 0.0397 for the haplotype combination of rs300996-snp-7057-rs300977 in the analysis of the quantitative effects of the alleles and haplotypes on IQ in females. Our data suggest that POU1F1 may affect MR through a gender-specific mechanism.
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PMID:Positive association between POU1F1 and mental retardation in young females in the Chinese Han population. 1650 1

Unrecognized congenital hypothyroidism leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. The primary thyroid-stimulating hormone screening has become standard in many parts of the world. However, newborn thyroid screening is not yet universal in some countries. Initial dosage of 10 to 15 microg/kg levothyroxine is recommended. The goals of thyroid hormone therapy should be to maintain frequent evaluations of total thyroxine or free thyroxine in the upper half of the reference range during the first 3 years of life and to normalize the serum thyroid-stimulating hormone concentration to ensure optimal thyroid hormone dosage and compliance. Improvements in screening and therapy have led to improved developmental outcomes in adults with congenital hypothyroidism who are now in their 20s and 30s. Thyroid hormone regimens used today are more aggressive in targeting early correction of thyroid-stimulating hormone than were those used 20 or even 10 years ago. Thus, newborn infants with congenital hypothyroidism today may have an even better intellectual and neurologic prognosis. Efforts are ongoing to establish the optimal therapy that leads to maximum potential for normal development for infants with congenital hypothyroidism. Remaining controversy centers on infants whose abnormality in neonatal thyroid function is transient or mild and on optimal care of very low birth weight or preterm infants. Of note, thyroid-stimulating hormone is not elevated in central hypothyroidism. An algorithm is proposed for diagnosis and management. Physicians must not relinquish their clinical judgment and experience in the face of normal newborn thyroid test results. Hypothyroidism can be acquired after the newborn screening. When clinical symptoms and signs suggest hypothyroidism, regardless of newborn screening results, serum free thyroxine and thyroid-stimulating hormone determinations should be performed.
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PMID:Update of newborn screening and therapy for congenital hypothyroidism. 1674 Aug 80

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.
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PMID:Newborn screening for congenital hypothyroidism. 1722 56

Hypothyroidism is known to be associated with mental retardation, motor dysfunction, memory deficits and hearing impairment. In the present study, the functional integrity of the thalamocortical projections to the primary auditory cortex and association cortex has been assessed by using Auditory Evoked Responses i.e Auditory Brainstem (ABR), Mid Latency Response (MLR) and Slow Vertex Response (SVR). Thirty newly diagnosed hypothyroid patients and thirty healthy controls were taken for the study and ABR, MLR and SVR were recorded on computerized evoked potential recorder using 10-20 system of electrode placement. The second recordings for the hypothyroid patients were done 3 months after treatment with attainment of euthyroid states. The present study revealed a slight increase in absolute latency of wave III of ABR in hypothyroid patients and significant decrease in absolute latency of wave III and interpeak latency of I-III after treatment. There was a significant decrease in amplitude of wave V in hypothyroid patients and significant increase in amplitudes of ABR wave I and wave V after treatment. There was a significant increase in latency of wave Na of MLR and wave P2 of SVR in hypothyroid patients. The latencies of waves Na, Pa, Nb of MLR and waves PI and N2 of SVR showed significant improvement with thyroid hormone treatment. The results of the present study indicates that in hypothyroid state there might be slow conduction at the periphery and with treatment there is better recruitment of neuronal pool of the generators of the waves of ABR in the brainstem. We can also conclude that the thalamocortical projections of the auditory pathways are adversely affected in the hypothyroid state and this improves after treatment.
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PMID:Functional status of auditory pathways in hypothyroidism: evoked potential study. 1740 63

Screening for thyroid hormone levels in the first week of life is extremely important to identify infants with CH. Worldwide neonatal screening programs have been successful in decreasing childhood mental retardation related to CH by early detection and treatment. To successfully screen for CH, nurses must understand how to draw blood that will yield valid results on the metabolic screening filter paper. It is also important for the nurse to understand that thyroid levels are normally decreased in preterm infants and that regular follow-up of those low thyroid levels is crucial because levels may return to normal and eventual treatment is necessary. Early follow-up testing and treatment are essential. A thyroid scan or ultrasonography is optional and decided on by evaluating the risk-benefit ratio.
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PMID:Thyroid hormone levels in term and preterm neonates. 1771 Sep 60


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