Disease relevance of Congenital Hypothyroidism

• A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate [1].
• CONTEXT: Iodide transport defect (ITD) is an autosomal recessive disorder resulting in varying degrees of congenital hypothyroidism (CH) with goiter and low or absent radioiodide uptake (RIUT), as determined by thyroid scintigraphy, and low iodide saliva to plasma ratio [2].
• When supplemented before conception, iodine prevents cretinism and folic acid reduces neural tube defect risks [3].
• We report on a male infant with congenital hypothyroidism owing to athyreosis occurring with the CHARGE association (bilateral papillary coloboma, congenital heart disease, dysmorphic ears, sensorineural deafness, psychomotor retardation, cryptorchidism, facial palsy, and vesicoureteral reflux) [4].
• We found familial dysalbuminemic hyperthyroxinemia (FDH) in a 5-month-old boy with congenital hypothyroidism (CH) who had a blood thyrotropin (TSH) level of 479 mU/L but normal total serum thyroxine (T4) and higher than normal total triiodothyronine (T3) levels [5].

Psychiatry related information on Congenital Hypothyroidism

• No significant difference was found for the auditory thresholds at conversational and high frequencies between 42 children with congenital hypothyroidism treated with L-thyroxine and an age-matched control group, regardless of the cause of the thyroid failure or hormone level and the age at the start of treatment [6].
• OBJECTIVE: Iodine deficiency is well known as the cause of several disorders such as endemic goitre and cretinism, along with a wide spectrum of psychoneurological development disorders including endemic mental deficiency and endemic cognitive deficiency, which are generally correlated to damage to the fetus [7].
• The effects of congenital hypothyroidism using the hyt/hyt mouse on locomotor activity and learned behavior [8].
• Thyroid hormone deficiency during the critical period of neural differentiation produces permanent and severe alterations in the morphology and function of the nervous system leading to cretinism [9].

High impact information on Congenital Hypothyroidism

• PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis [10].
• Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene [11].
• Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis [12].
• The estimation of T4 values supplemented by measurement of TSH values on specimens with low T4 values has proved to be a satisfactory approach to large-scale screening for congenital hypothyroidism [13].
• The occurrence of neurological symptoms and developmental delay in patients affected by congenital hypothyroidism (CH) has been attributed to the lack of thyroid hormone in the developing CNS [14].

Chemical compound and disease context of Congenital Hypothyroidism

• Maternal thyroxine and congenital hypothyroidism [15].
• Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site [16].
• The molecular basis of a total iodide organification defect causing severe congenital hypothyroidism has been elucidated [17].
• Cord blood reverse T3 in congenital hypothyroidism [18].
• Treatment of ovine cretinism in utero with 3,5-dimethyl-3'-isopropyl-L-thyronine [19].

Biological context of Congenital Hypothyroidism

• Using auditory brainstem response audiometry, we evaluated 34 congenital hypothyroidism children under thyroid hormone therapy and 24 age- and sex-matched controls between 5 and 12 yr of age [20].
• Furthermore, there is a murine strain (hyt) with congenital hypothyroidism and autosomal recessive inheritance, whose phenotype appears to be identical with the corresponding human disease [21].
• This polymorphism, which is located in an intervening sequence, was found in healthy individuals and in a family with hereditary congenital hypothyroidism due to a defect in the synthesis and structure of thyroglobulin [22].
• OBJECTIVE: To evaluate whether long-term L-thyroxine therapy in young adults with congenital hypothyroidism may affect bone mineral density (BMD) [23].
• The effects of congenital hypothyroidism in the late gestation ovine fetus include changes in serotonin concentrations in specific brain areas [24].

Anatomical context of Congenital Hypothyroidism

• Amniotic fluid 3,3',5'-triiodothyronine in the detection of congenital hypothyroidism [25].
• The loss of plasma membrane localization in mutated TPOs brought about the iodide organification defect, which was diagnosed as congenital hypothyroidism [26].
• CONCLUSIONS: The careful monitoring of serum thyroid-stimulating hormone and adjustment of l-thyroxine dosage avoided the significant deleterious effects of prolonged L-thyroxine replacement therapy on bone tissue in adolescents and young adults with congenital hypothyroidism treated from the neonatal period [23].
• The concentration of iodine in serum, urine, and breast milk in addition to thyrotropin (TSH), free thyroxine (FT(4)), and thyroglobulin was measured in 34 infants who were positive at congenital hypothyroidism screening [27].
• In the case of congenital hypothyroidism and normal maternal T(4), the transfer of the latter, together with increased D2 activity, protects the fetal brain from T(3) deficiency, even when it may be insufficient to maintain euthyroidism in other fetal tissues [28].

Gene context of Congenital Hypothyroidism

• Therefore, we screened for mutations in the TSHR gene in patients with congenital hypothyroidism and hypoplasia of the gland [29].
• A 20-basepair duplication in the human thyroid peroxidase gene results in a total iodide organification defect and congenital hypothyroidism [30].
• Expression of pituitary hormones in the Pax8-/- mouse model of congenital hypothyroidism [31].
• We have studied UPR development in two similar ERSDs, human congenital goiter caused by the C1264R and C1996S mutations in the thyroglobulin (Tg) gene and non-goitrous congenital hypothyroidism in rdw dwarf rats determined by the G2320R Tg mutation [32].
• Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH [33].

Analytical, diagnostic and therapeutic context of Congenital Hypothyroidism

• This condition may be 150-200 times more common than congenital hypothyroidism and ought to be prevented both by mass screening of free thyroxine in early pregnancy and by early iodine supplementation to avoid iodine deficiency, however mild [34].
• We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I), GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4 therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days, diagnosed by neonatal screening and in a group of age- and sex-matched control infants [35].
• In contrast to DIMIT's proven thyromimetic activity in other fetal animal models, this thyroid hormone analog failed to prevent cretinism in thyroidectomized fetal lambs even when administered to the ewe at a dose that suppressed maternal thyroid function [19].
• Radioimmunoassay of "free thyroxin" in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects [36].
• Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement [37].

References