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

Thyroid hormone exerts a powerful influence on CNS growth and maturation. Hypothyroidism early in life has long been known to cause disturbances in innate behavior, motor performance, severe and frequently irreversible mental retardation. In this deficiency, depressed caudate neurogenesis, cell migration and neuropil development during the rapid period of CNS growth may contribute to the clinical picture of perceptual handicaps often seen in cretins. Light microscopic and Golgi studies of the developing caudate nucleus in thyroid deficiency have been carried out to help attain insights into the mechanisms whereby the extrapyramidal system regulates motor function. The ultrastructural study of caudate nuclear cytogenesis and synaptogenesis in normal and hypothyroid states provides more detailed information for further analysis of the problem. Hypothyroidism was induced from birth by adding prophylthiouracil to the food and drinking water of lactating dams. Linear development of the caudate nucleus of both normal and hypothyroid rats at ages 8, 14, 20, 30 and 42 days was studied by electron microscopy. Thyroid glands were examined by light microscopy to assess the normal and deficient states. Immature cells, primitive processes and synapses were the characteristic features of the 8-day-old normal caudate nucleus. Distinctively wide cisternae of the rough endoplasmic reticulum, loosley packed Golgi apparatus and chromatin clumps throughout the nuclei of the neurons were significant early morphologic variations. The dramatic cytoarchitectural maturation in the 14- and 20-day normal caudate neuropil points to the rapidity of developmental rate. After the growth spurt of the first three weeks a maturational plateau occurs which is characterized by well-formed neuronal cytoplasmic organelles, myelinated and non-myelinated axons, axon terminals, dendrites and their spines, and synapses. Thyroid deficiency causes a marked maturational delay of approximately 7 days in caudate neuronal proliferation, the elaboration of neuronal networks and the attainment of mature synaptic contents and membranes. This delay is evidenced by comparison of the structural similarities between 8-day-old normal and 14-day-old deficient rats; and additional comparisons between the 14-day-old normal and 20-day-old hypothyroid rats. A rapid "catch up" process in fine structural morphogenesis takes place in the period between days 14 and 30 in the deficient animals. Repression of thyroid function does not entirely prevent development of the caudate nucleus but allows a fairly extensive, though critically incomplete degree of maturation. This imperfection is manifested by a decrease in the number of synaptic contacts that persists even after the rapid "catch up" phenomenon of caudate synaptogenesis.
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PMID:An electron microscopic study of the developing caudate nucleus in euthyroid and hypothyroid states. 86 26

Thyroid hormone deficiency is frequently associated with central nervous system (CNS) disturbances such as mental retardation, convulsions, coma etc. Studies of quantitative changes in CNS in hypo- or hyperthyroidism are scarce. Evoked potentials is a good method of assessing the electrical response of the brain to different (visual, acoustic, somatosensory) stimuli and has been used extensively in the study of brain disturbances and to a lesser degree in metabolic diseases. We studied the visual evoked potentials (latency and amplitude) in 12 patients with hyperthyroidism and 15 patients with hypothyroidism, before treatment and after they became euthyroid. Four of the hyperthyroids (33%) had abnormally prolonged (> 104 msec) latencies before therapy. Two of them had clinical exophthalmos. No change was observed after euthyroidism was achieved. On the contrary 7 out of 15 (47%) hypothyroids had abnormally prolonged latencies which became normal in 4 when euthyroidism was achieved. Amplitude was lower than normal in 6 and became normal only in one of them after treatment. None of the hyperthyroid patients had amplitude changes. In conclusion, hypothyroid patients may have changes in the amplitude and/or the latency of visual evoked potentials which are reversible to a great extent with thyroxine. Evoked potentials is another method of studying in humans the metabolic effects of thyroxine deficiency in CNS.
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PMID:Visual evoked potentials in hypothyroid and hyperthyroid patients before and after achievement of euthyroidism. 149 Nov 23

Two consecutive short gut babies with a residual small intestinal length of 44 and 46 cm, respectively, were managed initially by total parenteral nutrition and oral feedings begun around the fifth week postoperatively. Uncontrollable diarrhea, malabsorption, and failure to thrive made the early management of these babies a difficult problem. The two infants developed clinical features of hypothyroidism at the age of 4 and 6 mo, respectively. Hypothyroxinemia was confirmed by repeated detection of low serum levels of T4. Hormonal treatment resulted in clinical recovery and normalized T4 values. Thyroid function has remained normal after discontinuation of treatment, underlining the transient nature of hypothyroidism. Early recognition and therapy of this previously unreported association is essential in order to prevent mental retardation.
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PMID:Transient hypothyroidism associated with short gut syndrome. 707 72

Iodine is a trace element present in the human body in minute amounts (15-20 mg in adults, i.e. 0.0285 x 10(-3)% of body weight). The only confirmed function of iodine is to constitute an essential substrate for the synthesis of thyroid hormones, tetraiodothyronine, thyroxine or T4 and triiodothyronine, T3 (1). In thyroxine, iodine is 60% by weight. Thyroid hormones, in turn, play a decisive role in the metabolism of all cells of the organism (2) and in the process of early growth and development of most organs, especially of the brain (3). Brain development in humans occurs from fetal life up to the third postnatal year (4). Consequently, a deficit in iodine and/or in thyroid hormones occurring during this critical period of life will result not only in the slowing down of the metabolic activities of all the cells of the organism but also in irreversible alterations in the development of the brain. The clinical consequence will be mental retardation (5). When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur (Table 1), including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute an hindrance to the development of the affected population, are grouped under the general heading of Iodine Deficiency Disorders, IDD (6). Broad geographic areas exist in which the population is affected by IDD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iodine deficiency in Europe. 771 23

Resistance to thyroid hormone (RTH) is an inherited syndrome characterized by reduced tissue responsiveness to thyroid hormone. Subjects have elevated serum thyroid hormone levels in association with a nonsuppressed TSH. Goiter and thyroid test abnormalities have most often led to further investigation, underscoring the paucity of specific clinical manifestations of RTH. Hypothyroidism has been considered when growth or mental retardation was the presenting symptom and thyrotoxicosis when dealing with attention deficit or hyperactivity. Failure to recognize the inappropriate persistence of TSH secretion, in spite of elevated thyroid hormone levels, has commonly resulted in erroneous diagnosis leading to treatment aimed to normalize the thyroid hormone level. More than 400 subjects with this syndrome have been identified. The mode of inheritance appears to be autosomal dominant in the majority of families. It has long been suspected that RTH is most likely caused by an abnormal thyroid hormone receptor (TR), but this hypothesis could not be directly tested until the isolation of two TR genes, TR alpha and TR beta, located in chromosomes 17 and 3, respectively. TR beta gene mutations have been recently identified in 68 families with RTH. All mutations are located in the T3-binding domain, straddling the putative TR-dimerization region. Mutant TRs exhibit hormone-binding impairment, the degree of which does not correlate with the severity of clinical manifestations. This finding, and the fact that heterozygous subjects with complete TR deletion are not affected, while those with point mutations are, indicated that interactions of the mutant TRs with normal TRs and with other factors, are responsible for the dominant inheritance of RTH and its clinical heterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid 1994
PMID:Resistance to thyroid hormone: an historical overview. 783 74

This paper reviews present knowledge on the etiology, pathophysiology, complications, prevention, and therapy of the disorders induced by iodine deficiency. The recommended dietary allowances of iodine are 100 micrograms/day for adults and adolescents, 60-100 micrograms/day for children aged 1 to 10 years, and 35-40 micrograms/day in infants aged less than 1 year. When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute a hindrance to the development of the affected populations, are grouped under the general heading of iodine deficiency disorders (IDD). At least one billion people are at risk of IDD. Iodine deficiency, therefore, constitutes one of the most common preventable causes of mental deficiency in the world today. Most of the affected populations live in mountainous areas in preindustrialized countries, but 50 to 100 million people are still at risk in Europe. The most important target groups to the effects of iodine deficiency from a public health point of view are pregnant mothers, fetuses, neonates, and young infants because the main complication of IDD, i.e., brain damage resulting in irreversible mental retardation, is the consequence of thyroid failure occurring during pregnancy, fetal, and early postnatal life. The main cause of endemic goiter and cretinism is an insufficient dietary supply of iodine. The additional role of naturally occurring goitrogens has been documented in the case of certain foods (milk, cassava, millet, nuts) and bacterial and chemical water pollutants. The mechanism by which the thyroid gland adapts to an insufficient iodine supply is to increase the trapping of iodide as well as the subsequent steps of the intrathyroidal metabolism of iodine leading to preferential synthesis and secretion of triiodotyronine (T3). They are triggered and maintained by increased secretion of TSH, which is ultimately responsible for the development of goiter. The acceleration of the main steps of iodine kinetics and the degree of hyperstimulation by TSH are much more marked in the pediatric age groups, including neonates, than in adults, and the development of goiter appears as an unfavorable side effect in the process of adaptation to iodine deficiency during growth. The most serious complication of iodine deficiency is endemic cretinism, a syndrome characterized by irreversible mental retardation together with either a predominant neurological syndrome or predominant hypothyroidism, or a combination of both syndromes.(ABSTRACT TRUNCATED AT 400 WORDS)
Thyroid 1994
PMID:The disorders induced by iodine deficiency. 805 57

Congenital hypothyroidism (CH) is the most common cause of preventable mental retardation. Thyroid hormone deficiency in utero and in the first neonatal months is responsible for permanent damage. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH is important and highly recommended. At the moment, the Italian screening program for CH allows diagnosis and treatment within the first month of life. In Italy, screening programs became obligatory only a short time ago. In some regions, they started a few years ago, whereas in others they have been carried out only in an irregular way and only a part of the population has been investigated. Therefore CH was diagnosed just on the basis of clinical signs, with a consequent delay in the initiation of substitutive therapy. We describe the case of a little girl with CH diagnosed when she was three years old. We report the results of this case follow-up study and we describe the features of her neuropsychological development to point out her improvement and permanent disorders. The little girl was clearly hypothyroid with delayed achievement at three, but with pharmacological treatment she showed a dramatic amelioration in growth, language, motor skills and cognitive performances.
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PMID:[Missed diagnosis: a case of congenital hypothyroidism treated after three years]. 913 64

Permanent congenital hypothyroidism (CH) has an incidence of 1/3000-4000 newborns and is among the most frequent cause of mental retardation and neurological alterations in children. In 80% to 85% of cases CH is associated with thyroid dysgenesis. A group of 61 patients with CH (22 with agenesis, 18 with ectopy, 1 with hypoplasia, and 20 cases with CH without thyroid enlargement but not further characterized) and 30 normal subjects were examined for the presence of mutations in the gene encoding the thyroid transcription factor 1 (TTF-1). The coding-region of the TTF-1 gene was analyzed in all cases by the single stranded conformational polymorphism (SSCP) and no mutations were detected. Direct sequencing also carried out in patients with thyroid agenesis confirmed the absence of mutations or polymorphisms in the TTF-1 gene. The absence of mutations in the TTF-1 gene in our samples indicates that the mutations in the TTF-1 gene are not a frequent cause of CH.
Thyroid 1997 Jun
PMID:Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis. 922 98

Thyroid hormones are essential for normal behavioral, intellectual, and neurological development. Congenital hypothyroidism, if not treated, can result in irreversible mental retardation, whereas thyroid diseases with more moderate impairment of thyroid function, such as resistance to thyroid hormone, cause less severe intellectual and behavioral abnormalities, including attention deficit hyperactivity disorder. There is increasing evidence that exposure to certain synthetic compounds, including dioxins and polychlorinated biphenyls (PCBs), during the perinatal period can also impair learning, memory, and attentional processes in offspring. Animal and human studies suggest that exposure to these environmental toxicants impair normal thyroid function. Although the precise mechanisms of action of the adverse effects these toxicants have on neurodevelopment have not yet been elucidated, it is possible that they are partially or predominantly mediated by alterations in hormone binding to the thyroid hormone receptor. The convergence of studies that examine the neurodevelopmental consequences of moderate impairment of thyroid function, such as is found in resistance to thyroid hormone, with those studies that demonstrate the adverse behavioral and cognitive effects of perinatal exposure to dioxins and PCBs serves to generate new hypotheses to test in a research setting. Such studies may provide new insights into the basic pathogenesis of developmental neurotoxicity following exposure to thyroid-disrupting synthetic compounds.
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PMID:Resistance to thyroid hormone: implications for neurodevelopmental research on the effects of thyroid hormone disruptors. 946 Jan 71

Congenital hypothyroidism is a common preventable cause of mental retardation. The overall incidence is approximately 1:4000; females are affected about twice as often as males. Approximately 85% of cases are sporadic, while 15% are hereditary. The most common sporadic etiology is thyroid dysgenesis, with ectopic glands more common than aplasia or hypoplasia. While the pathogenesis of dysgenesis is largely unknown, some cases are now discovered to be the result of mutations in the transcription factors PAX-8 and TTF-2. Loss of function mutations in the thyrotropin (TSH) receptor have been demonstrated to cause some familial forms of athyreosis. The most common hereditary etiology is the inborn errors of thyroxine (T4) synthesis. Recent mutations have been described in the genes coding for the sodium/iodide symporter, thyroid peroxidase (TPO), and thyroglobulin. Transplacental passage of a maternal thyrotropin receptor blocking antibody (TRB-Ab) causes a transient form of familial congenital hypothyroidism. The vast majority of infants are now diagnosed after detection through newborn screening programs using a primary T4-backup TSH or primary TSH test. Screening test results must be confirmed by serum thyroid function tests. Thyroid scintigraphy, using 99mTc or 123I, is the most accurate diagnostic test to detect thyroid dysgenesis or one of the inborn errors of T4 synthesis. Thyroid sonography is nearly as accurate, but it may miss some cases of ectopic glands. If maternal antibody-mediated hypothyroidism is suspected, measurement of maternal and/or neonatal TRB-Ab will confirm the diagnosis. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, adjust the levothyroxine dose with growth to keep the serum T4 (or free T4) in the upper half of the normal range and the TSH normal, and maintain normal growth and development while avoiding overtreatment. An initial starting dose of 10-15 microg/kg per day is recommended; this dose will decrease on a weight basis over time. Serum T4 (or free T4) and TSH should be monitored every 1-2 months in the first year of life and every 2-3 months in the second and third years.
Thyroid 1999 Jul
PMID:Congenital hypothyroidism: etiologies, diagnosis, and management. 1044 22


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