1/175. Young-Simpson syndrome: further delineation of a distinct syndrome with congenital hypothyroidism, congenital heart defects, facial dysmorphism, and mental retardation.Young-Simpson syndrome is a rare congenital disorder, characterized by congenital hypothyroidism, congenital heart defects, facial dysmorphism, cryptorchidism in males, hypotonia, mental retardation, and postnatal growth retardation. We describe the cases of a 5-year-old boy and a 7-year-old girl with a similar constellation of symptoms and compared them with previously reported patients.- - - - - - - - - - ranking = 1keywords = thyroid (Clic here for more details about this article) |
2/175. 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 = 2keywords = thyroid (Clic here for more details about this article) |
3/175. Severe congenital hypothyroidism due to a homozygous mutation of the betaTSH gene.Isolated TSH deficiency leading to hypothyroidism seems to be a rare condition, escaping the diagnosis by neonatal screening programs, which are based on the primary determination of TSH. This is the first report of a case with an autosomal recessive TSH defect caused by a homozygous mutation of the betaTSH gene that was diagnosed in the early neonatal period. Hypothyroidism in the first child of apparently unrelated parents was suspected because of the classical symptoms of congenital hypothyroidism, which were fully expressed already on the 11th day of life. Routine neonatal TSH-screening on the 4th day of life had been normal, but subsequent determination of serum thyroid hormone levels revealed almost undetectable levels and thyroid hormone substitution was immediately started. Because there was no indication for other pituitary hormone deficiencies, sequence analysis of the betaTSH gene was initiated. A homozygous T deletion in codon 105 was found resulting in a change of a highly conserved cysteine to valine followed by eight altered amino acids and a premature stop codon due to the frame-shift. This altered betaTSH is a biologically inactive peptide. Because of the early development of severe symptoms, it is possible that this altered TSH suppresses the physiologic constitutive activity of the unliganded TSH receptor. Rapid molecular diagnosis in this patient clarified the diagnosis without additional endocrine and imaging studies and it is concluded, that symptoms of hypothyroidism in the neonatal period should result always in an immediate comprehensive work-up of thyroid function including molecular genetic studies irrespective of the screening result.- - - - - - - - - - ranking = 2.2keywords = thyroid (Clic here for more details about this article) |
4/175. congenital hypothyroidism with multiple ovarian cysts.A case of ectopic thyroid with congenital hypothyroidism presenting with bilateral multicystic ovaries without marked precocious puberty is reported. The cystic ovaries disappeared dramatically after thyroid hormone therapy. CONCLUSION: When ovarian cysts are found in prepubescent females, the possibility of associated hypothyroidism should be considered.- - - - - - - - - - ranking = 1.6keywords = thyroid (Clic here for more details about this article) |
5/175. A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.We previously reported nine children with an autosomally recessive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central canada. Since the original report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR products of each NIS (sodium/iodide symporter) gene exon with flanking introns amplified from genomic dna extracted from peripheral blood cells of the patients. We identified a novel NIS gene mutation, G395R (Gly395-->Arg; GGA-->AGA), in 10 patients examined in the present study. All of the parents tested were heterozygous for the mutation, suggesting that the patients were homozygous. The mutation was located in the 10th transmembrane helix. Expression experiments by transfection of the mutant NIS complimentary dna into COS-7 cells showed no perchlorate-sensitive iodide uptake, confirming that the mutation is the direct cause of the iodide transport defect in these patients. A patient who showed an intermediate saliva/serum technetium ratio (14.0; normal, > or = 20) and was considered to have a partial or less severe defect in the previous report (IX-24) did not have a NIS gene mutation. It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants.- - - - - - - - - - ranking = 0.6keywords = thyroid (Clic here for more details about this article) |
6/175. Hypomania in a patient with congenital familial hypothyroidism and mild mental retardation.This is a case of a 25-year-old lady with congenital familial hypothyroidism and mild mental retardation presenting with an affective psychosis. The occurrence of hypomanic symptoms in a severe hypothyroid state is unusual and only one other case has been reported. The possible etiological role of a sharp fall in circulating thyroxine levels and its effects on cerebral catecholamines is proposed.- - - - - - - - - - ranking = 1.2keywords = thyroid (Clic here for more details about this article) |
7/175. 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 = 4keywords = thyroid (Clic here for more details about this article) |
8/175. Severe intrauterine growth retardation, aged facial appearance, and congenital heart disease in a newborn with Johanson-Blizzard syndrome.We report a female newborn with Johanson-Blizzard syndrome associated with extreme intrauterine growth retardation, aged facial appearance, and atrial septal defect. Other features are microcephaly, prominent veins over the scalp, alopecia over the vertex, wide-open fontanelle, high forehead, antimongoloid slant, edematous eyelids, the absence of eyebrows and eyelashes, beaked nose with alae nasi, low-set ears, thin lips, and micrognathia. Investigations revealed deafness and congenital hypothyroidism. We believe that this association of severe intrauterine growth retardation and congenital heart disease represents the components of this syndrome.- - - - - - - - - - ranking = 0.2keywords = thyroid (Clic here for more details about this article) |
9/175. Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene.We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect.- - - - - - - - - - ranking = 1.2keywords = thyroid (Clic here for more details about this article) |
10/175. Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure.Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate regulator of thyroid and lung morphogenesis and function in humans. We report 2 female siblings with congenital thyroid dysfunction and recurrent acute respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3, resulting in haploinsufficiency for the NKX2.1 gene. This observation further supports a physiologic role for thyroid transcription factor-1 in early human thyroid and pulmonary function.- - - - - - - - - - ranking = 2.4keywords = thyroid (Clic here for more details about this article) |
| | Next -> |