1/45. Familial occurrence of congenital hypothyroidism due to lingual thyroid gland.Two sisters who presented with midline neck masses proved to be biochemically hypothyroid. Thyroid scintigraphy supplemented with perchlorate discharge testing showed lingual thyroid glands and ruled out the expected autosomal recessive organification defect. The related literature is reviewed.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
2/45. congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene.congenital hypothyroidism due to impaired thyroid response to TSH was originally described by Stanbury. A diagnosis of congenital hypothyroidism with thyroid unresponsiveness to TSH is accepted if the patient has congenital hypothyroidism, the thyroid gland is in the normal position in the neck, the size of the thyroid is either normal or atrophic, the serum TSH level is increased, the bioactivity of TSH is intact, and the response of the thyroid gland to TSH stimulation is decreased. In all originally described cases serum thyroglobulin was undetectable. We describe a 22-yr-old female patient who was severely hypothyroid and mentally retarded. serum T4 and T3 concentrations were below the sensitivity of the methods, with elevated serum TSH levels. serum thyroglobulin was undetectable. A normally shaped hypoplastic gland located in the appropriate anatomical position in the neck was found at scintiscan. The gland did not respond after administration of bovine TSH in terms of 131I uptake, serum thyroid hormones, and thyroglobulin secretion. A diagnosis of congenital hypothyroidism due to TSH unresponsiveness was formulated. Genetic analysis in the propositus showed a homozygous inactivating mutation of the TSH receptor that had not been previously described. The mutation consisted of the substitution of an isoleucine in place of a highly conserved threonine at position 477 in the first extracellular loop of the receptor (T477I). The brother, one sister of the father (whose dna was not available), the mother of the propositus, one sister, and the brother were heterozygous for T477I. All the heterozygous persons were unaffected. After transfection in COS-7 cells, the mutant receptor displayed an extremely low expression at cell surface. At variance with cells transfected with the wild-type TSH receptor, cells transfected with the mutant T477I did not show constitutive activity for the adenylyl cyclase pathway. A dramatic reduction in the amount of cAMP accumulation after bovine TSH challenge was observed in cells transfected with the mutant T477I receptor. A structural defect in the mutant TSH receptor protein was probably responsible for the poor routing of the receptor to the cell membrane. This is the first time that a loss of function mutation of the TSH receptor is described in a patient with severe congenital hypothyroidism and absent circulating thyroglobulin due to TSH unresponsiveness and the first time that an inactivating mutation of the TSH receptor is described in the first extracellular loop.- - - - - - - - - - ranking = 0.8keywords = gland (Clic here for more details about this article) |
3/45. A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child.congenital hypothyroidism associated with thyroid hypoplasia can be caused by several genetic defects, including mutations in the TSHbeta-subunit, the TSH receptor, the G(s)alpha-subunit, and the transcription factor PAX8. Four girls with sporadic congenital hypothyroidism and hypoplastic thyroid glands were analyzed for mutations in PAX8 and TTF2 (FKHL15). Mutations in the coding region of the TSHbeta-subunit gene, the TSH receptor gene, and exons 8 and 9 of G(s)alpha had been excluded previously. serum TSH concentrations were 150 mU/liter or more, TG levels were within normal limits, and thyroid autoantibodies were absent. technetium scintigraphies did not reveal the presence of thyroid tissue, but ultrasonography documented hypoplastic, normally located glands. One patient was found to harbor a heterozygous transversion 119A-->C in exon 3 of PAX8 replacing a conserved glutamine by proline in the paired box domain (Q40P). Analysis of her family members revealed that her mother, who has a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, is also heterozygous for this mutation. Functional analyses of the PAX8 Q40P mutation showed impaired binding to a PAX8 response element and absent trans-activation of a thyroid peroxidase promoter luciferase reporter gene. These findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. The absence of mutations in the coding sequences of the analyzed genes in the three other patients supports the concept that the pathogenesis of congenital hypothyroidism associated with thyroid hypoplasia is diverse.- - - - - - - - - - ranking = 0.6keywords = gland (Clic here for more details about this article) |
4/45. A familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene.Most of the time congenital hypothyroidism appears as a sporadic disease. In addition to the rare defects in hormonosynthesis associated with goiters, the causes of congenital hypothyroidism include agenesis and ectopy of the thyroid gland. The study of some familial cases has allowed the identification of a few genes responsible for congenital hypothyroidism. We report here a familial case of congenital hypothyroidism, transmitted as a recessive trait, and caused by a homozygous mutation in the thyrotropin receptor (TSH-R). The initial diagnosis of thyroid agenesis, based on the absence of tracer uptake on scintiscan, was incorrect, because ultrasound examination identified severely hypoplastic thyroid tissue in the cervical region.- - - - - - - - - - ranking = 0.2keywords = gland (Clic here for more details about this article) |
5/45. congenital hypothyroidism with prader-willi syndrome.We report a 1 year-old female patient with severe hypotonia who has congenital hypothyroidism and prader-willi syndrome (PWS). At birth she was found to have congenital hypothyroidism caused by an ectopic sublingual thyroid gland and was commenced on thyroid replacement therapy. She continued to have severe motor delay and therefore further diagnostic evaluation was performed. PWS was confirmed by dna and fluorescence in situ hybridization (FISH) analysis. This report emphasizes the need to further investigate patients who are found to have congenital hypothyroidism and do not improve adequately on treatment.- - - - - - - - - - ranking = 0.2keywords = gland (Clic here for more details about this article) |
6/45. An autosomal recessive syndrome of choanal atresia, hypothelia/athelia and thyroid gland anomalies overlapping bamforth syndrome, ANOTHER syndrome and methimazole embryopathy.Two sibs from an inbred Arab family are described with an autosomal syndrome of choanal atresia, hypothelia/athelia and thyroid gland anomalies overlapping Bamforth syndrome, ANOTHER syndrome and methimazole embryopathy. In one case the syndrome described was lethal. Cases with similar features are reviewed and genetic mutations discussed.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
7/45. A case of turner syndrome with congenital hypothyroidism untreated until age 38 years.OBJECTIVE AND methods: The effect of thyroid hormone on human growth and maturation is considered 'permissive'. To evaluate the effect of a prolonged thyroid hormone defect, especially in the pubertal period, a woman with untreated congenital hypothyroidism underwent studies of thyroid function and bone maturation for the first time at age 38 years 10 months and received thyroid hormone replacement. RESULTS: The karyotype was 45,X/46,XX. menstruation had occurred for 10 years, from menarche until she was about 31 years old. Epiphyseal closure of the left hand was incomplete. The serum thyroid hormone level was virtually undetectable, and her thyroid gland was not detectable in the normal position by ultrasonography. Her height increased by 3.5 cm in the first 9 months after starting thyroid hormone replacement; after 11 months, closure of the epiphysis was complete. CONCLUSION: Thyroid hormone is necessary to achieve bone maturation and epiphyseal closure, but its role is only permissive.- - - - - - - - - - ranking = 0.2keywords = gland (Clic here for more details about this article) |
8/45. The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population.congenital hypothyroidism (CH) occurs in approximately 1 in 3000 births and can be caused by mutations in 9 known genes, including that encoding the TSH receptor (TSHR). We report on two Welsh siblings, detected by neonatal screening, who had normal sized and placed glands but negative isotope uptake. Genomic dna was obtained from both siblings and parents, the TSHR amplified using pairs of intronic and/or overlapping exonic primers and the PCR products sequenced automatically. Both siblings were homozygous for a previously described G to A transition producing a missense mutation, W546X, in the fourth membrane spanning region of the TSHR, rendering it unresponsive to TSH. Both parents were heterozygous and unrelated; furthermore, the W546X has been described in three further families (one of which is Welsh), suggesting that it may be a relatively common mutation. We genotyped 368 euthyroid Welsh individuals using single nucleotide primer extension, and found 366 homozygous wild-type (G:G) and 2 heterozygous (G:A) for the mutation. In conclusion, CH in the siblings is due to the missense mutation, W546X, in their TSHR gene. The W546X allele was detected in approximately 1 in 180 individuals and may be a major contributor to hypothyroidism in the Welsh population.- - - - - - - - - - ranking = 0.2keywords = gland (Clic here for more details about this article) |
9/45. The longitudinal course of two cases with cretinism diagnosed after adolescence.In japan, mass screening tests on newborns for Cretinism have been performed since 1984, Cretinism is a very rare condition. We report the clinical course and complications of longitudinal thyroid hormone replacement therapy (liothyronine sodium: T3) of two women with Cretinism and ectopic thyroid gland for the past 33 years until 2001. They were born in April 1951 (Case 1) and in January 1952 (Case 2). On admission in June 1968, they were 17 and 16 years old. They had short stature, mental retardation, macroglossia, saddle nose, retardation of bone maturation, edematous face, coexistence of permanent teeth and deciduous teeth, abdominal distention, hypotonia, anemia, hypophosphatemia and hypercholesterolemia. After admission, Case 2 had an appendectomy for appendicitis. She was found to have a right ovarian cyst, but was not operated upon. Later, the right ovarian cyst disappeared during thyroid hormone replacement therapy. The complication in this case was NIDDM. Over secretion of thyroid hormone in for example, hyperthyroidism sometimes induces NIDDM. On their admission, a levothyroxine sodium (T4: Thyradin S) was unavailable in japan, so we had no choice but to treat them with liothyronine sodium for thyroid hormone replacement therapy. We suspect that liothyronine sodium replacement therapy probably induced NIDDM. They experienced improved bone maturation, anemia, hypophsphatemia and hypercholesterolemia, but their intellectual and mental disabilities were not improved.- - - - - - - - - - ranking = 0.2keywords = gland (Clic here for more details about this article) |
10/45. congenital hypothyroidism due to a new deletion in the sodium/iodide symporter protein.OBJECTIVE: Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS). PATIENT: We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long-term substitution therapy with L-thyroxine was started. MEASUREMENTS: Thyroid radioiodide uptake was only 1.4% and 0.3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I- ratio was 1.1 indicating that the inability of the thyroid gland to concentrate I- was also present in the salivary glands. RESULTS: Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439-443) which are located in the 6th intracellular loop. COS-7 cells transfected with a vector expressing the mutant del-(439-443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient. CONCLUSION: In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene.- - - - - - - - - - ranking = 0.8keywords = gland (Clic here for more details about this article) |
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