Case Of Congenital Hypothyroidism Research Articles

Correlação entre níveis de iodúria e TSH colhido em cordão umbilical de recém-nascidos do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo

The safest and most efficient way to diagnose congenital hypothyroidism (CH) is through screening programs using serum thyroid stimulating hormone (TSH). CH occurs in one in 1:2,300-1:5,000 births but higher rates are found in iodine-deficient areas. Iodine was measured in the urine of 141 newborns (87 males and 54 females) from Ribeirão Preto to complement the screening program developed by the School of Medicine of Ribeirão Preto (FMRP-USP) and Federal University of São Paulo (UNIFESP). TSH values did not disclose any case of CH, although we have seen an elevated ratio (0.96%) of calls for retests. The iodine urinary levels ranged from 2.1 to 194 microg/l (mean 58.3+/-36.2 microg/l). No differences between the levels of urinary iodine and gender or gestational ages were observed. A negative correlation between urinary iodine and TSH of blood from umbilical cord was found (r= -0.20, p= 0.02).

A New Case of Congenital Goiter with Hypothyroidism Caused by a Homozygous p.R277X Mutation in the Exon 7 of the Thyroglobulin Gene: A Mutational Hot Spot Could Explain the Recurrence of This Mutation

Identification of thyroglobulin (TG) gene mutations may provide insight into the structure-function relationship. In this study, we have performed molecular studies in a patient with congenital goiter, hypothyroidism, and impairment of TG synthesis. Genomic DNA sequencing revealed a homozygous c.886C-->T mutation in exon 7, resulting in a premature stop codon at amino acid 277 (p.R277X). The same nonsense mutation had been reported previously in two Brazilian families with multiple occurrence of congenital hypothyroidism with goiter. We compared the insertion/deletion polymorphism in intron 18, microsatellites (Tgm1, Tgm2, TGrI29, and TGrI30), and exonic single-nucleotide polymorphism haplotypes identified in the patient with a member of the previously reported family, who also carry the mutation as a compound heterozygous mutation. The single-nucleotide polymorphism and microsatellite analysis revealed that the two affected individuals do not share a common TG allele. This suggests that the p.R277X mutation is a mutational hot spot. No difference in either splicing or abundance of the amplified product was detected by RT-PCR, excluding that an alternative splicing mechanism, by skipping of exon 7, would restore the normal reading frame. In conclusion, we report a new case of congenital goiter and hypothyroidism caused by a p.R277X mutation in the TG gene. Moreover, we show that nucleotide 886 is a mutational hot spot that explains the recurrence of this mutation.

Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid.

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, a relatively frequent disease affecting 1 in 3000-4000 newborns. Whereas most cases are sporadic, mutations in transcription factors implicated in thyroid development have been shown to cause a minority of cases transmitted as monogenic Mendelian diseases. PAX8 is one of these transcription factors, and so far, five mutations have been identified in its paired domain in patients with thyroid dysgenesis. We have identified a novel mutation of PAX8, in the heterozygous state, in a father and his two children both presenting with congenital hypothyroidism associated with an in-place thyroid of normal size at birth. In addition, one of the affected siblings displayed unilateral kidney agenesis. The mutation substitutes a highly conserved serine in position 54 of the DNA-binding domain of the protein (S54G mutation) by a glycine. Functional analyses of the mutant protein (PAX8-S54G) demonstrated that it is unable to bind a specific cis-element of the thyroperoxidase gene promoter in EMSAs and that it has almost completely lost the ability to act in synergy with Titf1 to transactivate transcription from the thyroglobulin promoter/enhancer. These results indicate that loss of function mutations of the PAX8 gene may cause congenital hypothyroidism in the absence of thyroid hypoplasia.

Werdnig–Hoffmann disease with congenital hypothyroidism

Congenital hypothyroidism is often associated with other congenital anomalies. In some instances it is difficult to differentiate congenital hypothyroidism from Werdnig-Hoffmann's disease. We report a case of congenital hypothyroidism associated with Werdnig-Hoffmann's disease that appears to be the first of its kind in the literature.

Thyroid Abnormalities as a Feature of DiGeorge Syndrome: A Patient Report and Review of the Literature

DiGeorge syndrome or anomaly consists of a developmental field defect which is characterized by congenital absence or hypoplasia of the thymus and parathyroids, as well as facial dysmorphism and congenital heart defects. Other congenital malformations may coexist, in particular, thyroid abnormalities. A case of congenital hypothyroidism and DiGeorge syndrome is reviewed. Necropsy, clinical, and experimental studies also show that thyroid abnormalities may be a feature of DiGeorge syndrome. Although this could be purely coincidental, our case suggests that thyroid gland dysgenesis may be more common than previously thought. Thus, children with the DiGeorge syndrome may be at higher risk for hypothyroidism. Because of this potential association, patients who are considered to have this anomaly should have early newborn thyroid screening.

An audit of infants ‘unscreened’ by the neonatal screening system in Scotland during 1991

Introduction: The aim of this study was to assess the number of infants born in Scotland from whom a newborn screening specimen did not arrive at the screening laboratory. Methods: In a systematic 1 in 8 sample, records on 8379 babies registered as born during 1991, were supplied by the Office of the Registrar General (Scotland). These were matched with records from the neonatal screening laboratory database. For all unmatched records, local health board offices were phoned for evidence of a negative result. Results: Specimens from 8324 of these babies were received and tested by the screening laboratory. Of the remaining 55 babies, 34 had died within 24 h of birth, five had returned home (three to England and Wales and two to outside the United Kingdom), four refused for parental objection (three were Jehovah's Witnesses), and 12 were unscreened. Thus, only 0.14% (12 of 8379 of registered infants (95% Confidence Interval 0.22, 0.06)) were unscreened by the Inborn Errors Screening Program in Scotland during 1991. Discussion: From this study, an estimated 96 infants were unscreened for newborn screening (95% Confidence Interval 39, 143) of 67032 infants registered as born in Scotland during 1991. At this rate, a case of congenital hypothyroidism or phenylketonuria would be missed only every 47 and 78 years, respectively, as a result of having been unscreened by the program. Improvement is expected from regular audit now underway. The rate of 0.14% for Scotland is much lower than the rate of 0.82% estimated for unscreened infants in the New York State Newborn Screening Program.

Thyroid Hemiagenesis Accompanying an Ectopic Sublingual Thyroid

The authors report a case of congenital hypothyroidism. The patient's Tc-99m pertechnetate thyroid study revealed an unusual image: thyroid hemiagenesis accompanying an ectopic sublingual thyroid.

Congenital hypothyroidism screening and the cutoff for thyrotropin measurement: recommendations from The Netherlands.

There is little agreement as to the optimal cutoff point for thyrotropin testing in primary thyroxine screening programs for congenital hypothyroidism. Most programs in the United States use a cutoff point of 10% of the lowest thyroxine values, whereas in the Netherlands a cutoff point of 20% is used. Therefore, the results of the Dutch program may provide valuable information about the optimal cutoff point. The frequency distribution of screening thyroxine values was studied in all cases of permanent primary congenital hypothyroidism (n = 481) detected in 1,601,603 screened children born during the period from January 1, 1981, to December 31, 1989, in the Netherlands. Programs using a 10% cutoff point would have missed 1.5% of cases. Above the 10% cutoff point, the marginal costs increase quite rapidly because of the escalating numbers of thyrotropin measurements necessary to detect one case of permanent primary congenital hypothyroidism: 20,000 in the range of 11% to 15% and 40,000 in the range of 16% to 20%. Based on these findings, a cutoff point of at least 10% is recommended.

Congenital Hypothyroidism and Cystic Fibrosis

We report a case of dysgenetic congenital hypothyroidism associated with cystic fibrosis. Impaired exocrine pancreatic secretion and/or transit abnormalities secondary to the treatment of meconium ileus resulted in decreased absorption of L-thyroxine and difficulties in management of hypothyroidism.

A Case of Congenital Hypothyroidism Due to Thyroid Hypoplasia

A Case of Congenital Hypothyroidism Due to Thyroid Hypoplasia

Immunofluorometry of thyrotropin, from whole-blood spots on filter paper, to screen for congenital hypothyroidism.

We have evaluated a time-resolved immunofluorometric assay (IFMA) for determining thyrotropin. This "sandwich"-type system involves two monoclonal antibodies directed against different epitopes. A linear relationship between signal and thyrotropin concentration was observed up to 6000 milli-int. units/L. This procedure takes one day, vs six days with our present RIA technique, and requires only a tenth as much sample. Furthermore, intra- and interassay CVs are lower than with RIA. Assay of 19 paper-disc blood specimens from newborns identified as having congenital hypothyroidism, both by RIA and by clinical evidence, also gave positive results with IFMA. In prospective assay of 3944 specimens by both methods we identified one case of congenital hypothyroidism, which was detected by both techniques. Technical false-positive reactions, identified as such by repeated analyses, were fewer with the IFMA method than with RIA.

Descriptive Epidemiology of Missed Cases of Phenylketonuria and Congenital Hypothyroidism

We conducted a structured telephone survey of state public health laboratory directors of neonatal screening programs to determine the extent of the problem of missed cases of phenylketonuria (PKU) and congenital hypothyroidism. A total of 76 missed cases were reported--43 PKU and 33 congenital hypothyroidism. We looked at the following characteristics of the missed cases: the stage at which the miss occurred, which included specimen collection, laboratory procedures, or follow-up; the size of the program; the type of screening program; the age of the infant at the time of screening; and any legal action that resulted from the miss. The 76 missed cases probably represent an underascertainment of the true number, yet we believe that our data provide an overview of some of the problems associated with mass neonatal screening. There was one missed case of PKU for every 70 cases detected, and one missed case of congenital hypothyroidism for every 120 cases detected; in other words, two congenital hypothyroidism cases were missed for every 1 million infants screened. Regarding the stage of screening in which the miss occurred, 14% occurred during specimen collection, 45% during the laboratory procedures stage, 16% during follow-up, 11% were the result of biologic variation, and in 14% the stage could not be identified. We conclude that neonatal screening programs have been highly successful but that there may be additional safeguards to be developed, tested, and implemented when practical.

Peptide-linked iodotyrosines and iodothyronines in the blood of a patient with congenital goiter.

A case of congenital goitrous hypothyroidism is reported. Studies were made to determine whether a metabolic defect was present. Intravenously administered I131-labeled diiodotyrosine and thyroxine were metabolized normally. Electrophoresis of plasma proteins after in vitro addition of I131-labeled thyroxine demonstrated normal amounts of thyroxine-binding protein. I131 was rapidly concentrated by the gland, and administration of potassium thiocyanate did not cause the release of trapped iodide. Endogenously labeled material in the serum was 60–65 per cent insoluble in butanol. The soluble fraction proved to be thyroxine and triiodothyronine. Starch-block electrophoresis and ultracentrifugation identified the butanol-insoluble portion as an abnormal iodinated protein having the mobility of albumin. This protein was not precipitated by equine anti-human serum albumin. After enzymatic hydrolysis of plasma, mono- and diiodotyrosine, thyroxine, and triiodothyronine were identified on paper chromatograms. This...