141/184. dopamine suppresses thyroid-stimulating hormone secretion in neonatal hypothyroidism. The infusion of dopamine, a hypophysiotropic catecholamine, which inhibits release of thyroid stimulating hormone (TSH), is the inotropic therapy of first choice in neonatal intensive care. Newborns with primary hypothyroidism are at increased risk of cardiocirculatory morbidity and are screened by measuring serum TSH concentrations. In an infant with both congenital heart disease and neonatal hypothyroidism, withdrawal of dopamine infusion was documented to evoke a doubling of serum TSH levels within 40 min, a finding suggestive of an inhibitory effect of dopamine administration on neonatal TSH hypersecretion. As a result, dopamine therapy may be a pitfall in TSH screening for neonatal hypothyroidism. ( info) |
142/184. Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype. The combined deficiency of thyrotropin, growth hormone and prolactin, caused by PIT1 abnormality manifests in the homozygous or heterozygous state. We studied a patient having an allele with Arg271Trp mutation, which produces clinical symptoms in heterozygotes by a dominant-negative effect. However, in the family, her father, grandmother and aunts had the same mutation without clinical symptoms, although the proband had typical phenotypic expression. We analyzed the PIT1 transcript in peripheral lymphocytes by reverse transcription-polymerase chain reaction and found monoallelic expression of normal allele in the father and grandmother and skewed pattern of biallelic expression in the proband. The phenotypic expression of PIT1 abnormality may depend on different transcription of the PIT1 gene. ( info) |
143/184. Measurement of TSH receptor blocking immunoglobulins using 3H-adenine incorporation into FRTL-5 and JPO9 cells: use in a child with neonatal hypothyroidism. OBJECTIVE: The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H-cAMP production following incubation of FRTL-5 or JPO9 cells with 3H-adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism. DESIGN: The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding inhibitory antibodies), and the thyroid antibodies anti-thyroid peroxidase and thyroglobulin antibodies were measured in both mother and child over a 6-month post-natal period. PATIENT: The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Hashimoto's thyroiditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid. RESULTS: Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum. CONCLUSIONS: This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism. ( info) |
144/184. Iodide-trapping defect of the thyroid. A case report. We describe a grossly hypothyroid 50-year-old woman, mentally retarded since birth. On the basis of her history of recurrent goitre, absence of 131I neck uptake and a low saliva/plasma 131I ratio, congenital hypothyroidism due to a defect of the iodide-trapping mechanism was diagnosed. Other family members studied did not have the defect. ( info) |
145/184. Cretinism after weekly dosing with levothyroxine for treatment of congenital hypothyroidism. An 11-month-old infant was treated elsewhere for congenital hypothyroidism with weekly doses of levothyroxine. The infant had cardinal features of cretinism including poor growth, delayed skeletal maturation, and mental retardation. Treatment of such infants with weekly doses of levothyroxine cannot be justified. ( info) |
146/184. A 20-basepair duplication in the human thyroid peroxidase gene results in a total iodide organification defect and congenital hypothyroidism. In this study we present the molecular basis of a total iodide organification defect causing severe congenital hypothyroidism. In the thyroid gland of the patient, thyroid peroxidase (TPO) activity and the iodination degree of thyroglobulin were below detection limits, and no TPO messenger ribonucleic acid was detectable by Northern blot analysis. Denaturing gradient gel electrophoretic analysis of the TPO gene of the patient revealed a homozygous mutation in exon 2. sequence analysis showed the presence of a 20-basepair duplication, 47 basepairs down-stream of the ATG start codon. This duplication generates a frame shift, resulting in a termination signal in exon 3, compatible with the complete absence of TPO. Both parents of the patient are heterozygous for the same duplication, confirming the recessive mode of inheritance of the mutation. ( info) |
147/184. Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibiting immunoglobulin. Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibitor immunoglobulin (TBII), a thyroid-stimulating hormone (TSH)-receptor blocking antibody, is described in three male siblings born to a mother with autoimmune thyroiditis. These cases are believed to be the first described in australia. The first child was found to have a serum TSH of 565 mU/L and had a negative thyroid scan when presented for neonatal screening. He was treated with thyroxine but became thyrotoxic at 3 months of age when he was on a dosage of 85 micrograms/m2 of body surface area. He was euthyroid 6 months after discontinuation of therapy. Nine years later a second hypothyroid sibling was born, with a serum TSH of 709 mU/L on day 4. Both mother and child were demonstrated to be strongly positive for TBII. Again this child was able to cease therapy by the age of 9 months. A third sibling, also TBII positive, was born 12 months after the second. His TSH was 90 mU/L and his serum thyroxine (T4) was 169 nmol/L. On this occasion, thyroid stimulation-blocking antibody was found to be present in the serum of both mother and child. thyroxine therapy was ceased at 1 month. The family present a picture of varying degrees of transient neonatal hypothyroidism due to the transplacental passage of a maternal receptor blocking antibody. The condition is self-limiting, resolving when the immunoglobulin is cleared from the infant's circulation. ( info) |
| Thyroid dysfunction is rare in tuberous sclerosis, although papillary adenomas (hamartomas) of the thyroid gland have been reported in a few autopsy cases. We describe a child with tuberous sclerosis and primary congenital hypothyroidism secondary to a dysgenetic thyroid gland. To our knowledge, this association has not been reported previously. Although the association of these two disorders in one patient may be merely coincidence, we speculate that the dysgenetic thyroid gland in this patient may represent a "hamartia" as a consequence of the tuberous sclerosis gene. ( info) |
149/184. Necrotizing enterocolitis and hypothyroidism in a newborn infant: treatment with intravenous L-thyroxine. Gastrointestinal complications of hypothyroidism are well documented and include constipation, obstipation, and abdominal distention, as well as ileus, pseudo-obstruction, tumor-like mass of the intestine, and megacolon. We report herein on a 2-week-old, full-term female infant, who had both necrotizing enterocolitis (NEC) and congenital hypothyroidism. We further describe the response to therapy with intravenous L-thyroxine. To our knowledge, the patient's course is the first report of intravenous L-thyroxine in the management of congenital hypothyroidism when oral replacement is not an option. The possible causal relationship between NEC and hypothyroidism is discussed. ( info) |
150/184. 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). ( info) |