1/8. Transdifferentiation of somatotrophs to thyrotrophs in the pituitary of patients with protracted primary hypothyroidism.In patients with protracted primary hypothyroidism, the pituitary is enlarged due to the lack of feedback inhibition by thyroid hormone. In the present work, adenohypophysial biopsies from three women with protracted primary hypothyroidism were investigated by routine histology, immunocytochemistry, double immunostaining, immunoelectron microscopy, and combined immunocytochemistry - in situ hybridization. These methods confirmed the presence of massive thyrotroph hyperplasia and the formation of "thyroidectomy" or "thyroid deficiency" cells. A number of thyroidectomy cells were found to be immunoreactive for growth hormone (GH). Double immunostaining and immunoelectron microscopy revealed the presence of bihormonal cells containing both GH and thyroid stimulating hormone (TSH). Immunostaining combined with in situ hybridization revealed GH immunoreactive cells expressing TSH mRNA as well as TSH immunopositive cells expressing GH mRNA. Our findings provide conclusive evidence that somatotrophs may transform to thyrotrophs. Thus, in addition to multiplication of thyrotrophs, transdifferentiation of GH cells to thyrotrophs contributes to the increase of TSH-producing cells. The presence of such bihormonal cells best termed "thyrosomatotrophs" supports the concept that adenohypophysial cells are not irreversibly committed to the production of one single hormone and that their phenotype can change in response to functional demand.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. trisomy 7p resulting from 7p15;9p24 translocation: report of a new case and review of associated medical complications.The authors report on a young girl with generalized developmental deficits originally thought to be caused by an unusual reaction to DPT vaccination. At the age of 4(1/2) years, chromosome analysis showed that the terminus of the short arm of chromosome 9 had extra material believed to originate from 7p terminus, thus she was considered to be trisomic for a segment of 7p and monosomic for a small portion of 9p [46,XX,der (9), t(7;9)(p15;p24)]. Ten years later, molecular cytogenetic testing using fluorescence in situ hybridization (FISH) confirmed that the extra chromosomal material represented partial trisomy 7p. The proposita had a high and large forehead, hypertelorism, and broad nasal bridge, findings seen in most individuals with trisomy 7p. Long-term follow-up showed the presence of hypothyroidism, obesity, and cerebral palsy. A review of all published cases of trisomy 7p with focus on associated complications suggests a well-defined pattern of abnormalities characterized by musculoskeletal, cardiovascular, neurological, genital, and ocular abnormalities in decreasing frequency. At least one-third of affected individuals died in infancy and close to half had severe mental retardation. FISH was essential in the confirmation of the cytogenetic abnormality and further delineation of the chromosomal disorder.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/8. 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 = 0.5keywords = hybridization (Clic here for more details about this article) |
4/8. New case of thyroid dysgenesis and clinical signs of hypothyroidism in williams syndrome.The authors report a female presenting with congenital heart defects, liver hemangiomas, and facial dysmorphisms admitted to hospital at 3 months of age because of feeding difficulties and poor growth. She had hypotonia and large tongue, "coarse" face, and umbilical hernia in presence of complex congenital cardiovascular malformations. In spite of normal neonatal screening we performed serum levels of thyroid hormones. thyrotropin level was very high (>50 microU/ml; normal value 0.2-4 microU/ml), while serum free T(3) (FT3) and free T(4) (FT4) levels were normal (FT3 3.6 pg/ml, normal value 2.8-5.6 pg/ml; FT4 11.6 pg/ml, normal value 6.6-14 pg/ml); antithyroid autoantibodies were absent. Thyroid scintigraphy with sodium 99m Tc pertechnetate showed a small ectopic thyroid located in sublingual position, so treatment with L-thyroxine 37.5 microg/24 hr was started with rapid improvement of the clinical picture. At 17 months of age the patient developed the complete characteristic phenotype of williams syndrome (WS); the clinical diagnosis was proven by fluorescent in situ hybridization (FISH) analysis which showed hemizygous deletion of the elastin gene on chromosome 7. Recently a case of thyroid hemiagenesis in a child with WS has been reported; our patient underscores the association of hypothyroidism and WS. Moreover, our case shows that clinical manifestations of hypothyroidism may be present and the treatment may be necessary as it is in isolated congenital hypothyroidism.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
5/8. Normal thyroglobulin and thyroperoxidase gene expression in thyroid congenital defective thyroglobulin synthesis.We have studied a member (JBM) of a family MO previously described, with congenital goiter, hypothyroidism, and presence of hyposialylated Tg in the follicular lumen. Other congenital goiters (MA and JNA) with virtual absence of Tg were studied similarly. The presence of apparently normal-sized Tg in JBM tissue was confirmed in the present study by radioimmunoassay, Sephacryl S300 column chromatography, immunoelectrophoresis, and SDS agarose gel electrophoresis. Dot blot hybridization analysis with Tg and TPO probes indicated that mRNA hybridization levels of JBM tissue were similar to control thyroid tissues. Congenital goiter tissues showed relatively lower TSH receptor mRNA content in comparison with normal thyroid tissues. dna was digested with five restriction endonucleases (Taq I, Eco Rv, Pvu II, Pst I, and Eco RI), and the results revealed polymorphisms previously described with the Tg gene. No significant differences in the TPO Pst I pattern were observed in comparison with control samples. We conclude that no major alterations of the Tg and TPO gene expression are detectable and that no significant deletions of these genes are present. The biochemical abnormality in the JBM Tg molecule may be a posttranslational error during the assembly of the protein.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/8. Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis.We characterized the virtual absence of immunoassayable thyroglobulin (Tg) in the serum and thyroid gland of two siblings (MA, JNA) and one nephew (RSS) from a family without inbreeding or familial goiter. diagnosis of defective Tg gene expression was based on findings of normal PBI and low serum T4, low or normal serum T3, negative perchlorate discharge test, and virtual absence of the serum Tg response to challenge by bovine TSH. This conclusion was confirmed by analysis of proteins in the goiter extracts. Only minute amounts of immunoassayable Tg were detected by RIA (MA, 0.11; JNA, 0.19 mg/g tissue; compared to 70-90 mg/g in normal thyroid tissue). Gel filtration in Sephacryl S300 showed the absence of a normal Tg peak at 280 nm and concentration of label mostly on albumin. A minor intermediate peak of radioactivity was also detected, with the size of, approximately, normal Tg. sodium dodecyl sulfate-agarose gel electrophoresis indicated the absence of Tg dimer and monomer, and Western blotting and immunoelectrophoresis confirmed this finding. Dot blot quantification of Tg and thyroid peroxidase mRNA indicated decreased hybridization of the patients' mRNA (MA, 44%; JNA, 63%) with phTgM2 (Tg probe) and increased hybridization (MA, 191%; JNA, 182%) with the pM5 (thyroid peroxidase probe) compared with control thyroid tissue. Dot blot analysis of Tg mRNA from the two siblings weakly hybridized with 3' and 5' Tg probes. RNA analysis by means of Northern transfer showed a clear signal of hybridization with Tg probe (phTgM1) in the 8- to 9-kilobase range, corresponding to the normal size Tg mRNA. No major polymorphisms were noted in Southern blotting, using seven restriction endonucleases. We conclude that no gross alteration of the 5' region of Tg gene was present in these patients. Ultrastructural examination of the thyroid tissue indicated that the rough endoplasmic reticulum was not augmented, nor were the cisternae of rough endoplasmic reticulum dilated. The defect observed in these goiters is diminished tissue concentration of Tg mRNA with defective translation. However, small amounts of functionally active Tg could be synthesized, iodinated, and immediately hydrolized, yielding mostly T3, owing to the intense tissue stimulation by TSH.- - - - - - - - - - ranking = 1.5keywords = hybridization (Clic here for more details about this article) |
7/8. Two patients with overlapping de novo duplications of the long arm of chromosome 9, including one case with Di George sequence.Duplications of chromosome 9q are rare. We describe the cytogenetic and phenotypic findings in 2 patients, one with a large duplication covering most of 9q(q12-q33.2) and one with a smaller duplication (q21.12-q22.1) who had Di George sequence (DGS). The chromosome 9 origin of the extra material in the second case was confirmed by fluorescence in situ hybridization (FISH) analysis with a whole chromosome 9 paint. Microdeletions of chromosome 22 are common in DGS and have been reported in CHARGE association. This is the first report of an association of a chromosome 9 abnormality with DGS in the absence of a chromosome 22 abnormality and the seventh report of a patient with a duplication of a large portion of 9q (q11-q13 to q32-q33).- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
8/8. Evidence for the segregation of three different mutated alleles of the thyroglobulin gene in a Brazilian family with congenital goiter and hypothyroidism.We have previously reported a Brazilian family with congenital goiter, hypothyroidism, and marked impairment of thyroglobulin (Tg) synthesis. Analysis of the Tg mRNA in the goiter of one of the siblings revealed a cytosine to thymine transition creating a stop codon at position 1510. This point mutation is removed from the majority of Tg mRNA transcripts by the preferential generation in the goiter of a 171 nt deleted Tg mRNA by alternative splicing. The nonsense mutation destroys a TaqI site at this position in the mutant Tg gene. Using polymerase chain reaction (PCR) amplification and TaqI digestion we found that two siblings affected with goiter and hypothyroidism, as well as the father and three siblings with normal thyroid function, are all heterozygous for the nonsense mutation. This implies that an additional mutation must be present in the affected individuals, generating a compound heterozygote genotype. A new polymorphism within the thyroglobulin gene represented by three alleles has been detected. This was documented by the TaqI restriction enzyme and phTgM3 probe hybridization that showed a three allelic polymorphism with fragment sizes of 16.5 kb (allele A), 14.5 kb (allele B) and 11.0 kb (allele C). Segregation analysis of these alleles in the family indicated that the two affected siblings were homozygous for the allele C. In contrast the unaffected father and three other siblings, who carried the nonsense mutation, were heterozygous for alleles B and C. Analysis of the Tg genotypes implies that two additional mutations of the Tg gene must segregate in this family to account for the observed phenotypes.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |