Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection.

Background/aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought.

[Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases].

Congenital hypothyroidism affects 1:2000-3000 newborns detected by neonatal screening programs. Dual oxidases, DUOX1 and 2, generate hydrogen peroxide needed for the thyroid hormone synthesis. Hipotiroidismo congénito transitorio por defectos bialélicos del gen DUOX2.

Differentiated Thyroid Cancer in Children: Prevalence and Predictors in a Large Cohort with Thyroid Nodules Followed Prospectively.

We retrospectively analyzed the findings of a prospective cohort of 75 children referred for thyroid nodules between 2008 and 2013. Prevalence of papillary differentiated thyroid carcinoma was 18.7%.

Prevalence and etiology of congenital hypothyroidism detected through an argentine neonatal screening program (1997-2010).

Introduction: We retrospectively assessed the incidence of congenital hypothyroidism (CH) detected through our neonatal screening program between 1997 and 2010. We describe the diagnostic characteristics of the detected population and verify the impact of a TSH cutoff (CO) change.

Patients And Methods: Screening was based on TSH determination on dried blood spot on filter paper samples (IFMA) using a 15 mU/l blood CO until 12/2002 (P1) and 10 mU/l thereafter (P2).

Severe congenital non-autoimmune hyperthyroidism associated to a mutation in the extracellular domain of thyrotropin receptor gene.

Activating mutations in the TSH Receptor (TSHR) gene have been identified as the molecular basis for congenital non-autoimmune hyperthyroidism. We describe the clinical findings and molecular characterization in a girl who presented severe non-autoimmune hyperthyroidism since birth, born to a mother with autoimmune thyroid disease. She was treated with methylmercaptoimidazol and β-blockers, but remained hyperthyroid and required total thyroidectomy.

New insights into thyroglobulin gene: molecular analysis of seven novel mutations associated with goiter and hypothyroidism.

The thyroglobulin (TG) gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. Up to now, 62 inactivating mutations in the TG gene have been identified in patients with congenital goiter and endemic or non-endemic simple goiter. The purpose of the present study was to identify and characterize new mutations in the TG gene.

Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene.

Background: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25.

Variable clinical presentation and outcome in pediatric patients with resistance to thyroid hormone (RTH).

Resistance to thyroid hormone (RTH) is characterized by elevated levels of thyroid hormones, normal or slightly increased TSH levels respondent to TRH, resistance to thyroid hormone administration, and variable clinical expression. To describe the diverse clinical and biochemical findings of six children from five unrelated families with molecular diagnosis of RTH (0.5-12.

Clinical, biochemical, and molecular findings in Argentinean patients with goitrous congenital hypothyroidism.

We describe the clinical, biochemical, and molecular findings of a cohort of Argentinean patients with congenital hypothyroidism (CH) and goiter studied to characterize iodide organification and thyroglobulin (TG) defects. 20 CH patients (16 unrelated) were grouped according to serum TG levels and a perchlorate discharge test (PDT) in: group 1 (G1): nine patients with high TG and PDT > 10% who were studied for tiroperoxidase (TPO), dual oxidase 2 (DUOX2), and dual oxidase A2 (DUOXA2) defects and group 2 (G2): 11 patients with low TG and PDT < 10% studied for TG defects. Goiter characteristics, outcome, and TT₄ and TT₃ levels without treatment were compared between groups.

17alpha-hydroxyprogesterone and cortisol serum levels in neonates and young children: influence of age, gestational age, gender and methodological procedures.

To determine the influence of age, gestational age, gender and methodological protocol on serum 17OHP and cortisol concentrations. 17OHP in non-extracted (NE) and extracted (E) sera was measured by RIA in 319 full-term (FT) (1 d-5 yr) infants, 38 pre-term (PT) and in 19 neonates with classical CAH at diagnosis. 17OHP (NE- and E-) decreased with age in normal children.

Molecular analysis of congenital goitres with hypothyroidism caused by defective thyroglobulin synthesis. Identification of a novel c.7006C>T [p.R2317X] mutation and expression of minigenes containing nonsense mutations in exon 7.

Background: Thyroglobulin (TG) deficiency is an autosomal-recessive disorder that results in thyroid dyshormonogenesis. A number of distinct mutations have been identified as causing human hypothyroid goitre.

Objectives: The purpose of this study was to identify and characterize new mutations in the TG gene in an attempt to increase the understanding of the genetic mechanism responsible for this disorder.

Genotyping of resistance to thyroid hormone in South American population. Identification of seven novel missense mutations in the human thyroid hormone receptor beta gene.

Thyroid Hormone Receptor beta (THRB) defects, typically transmitted as autosomal dominant traits, cause Resistance to Thyroid Hormone (RTH). We analyzed the THRB gene in thirteen South American patients with clinical evidence RTH from eleven unrelated families. Sequence analysis revealed seven novel missense mutations.

Recurrence of the p.R277X/p.R1511X compound heterozygous mutation in the thyroglobulin gene in unrelated families with congenital goiter and hypothyroidism: haplotype analysis using intragenic thyroglobulin polymorphisms.

Thyroglobulin (TG) functions as the matrix for thyroid hormone synthesis. Thirty-five different loss-of-function mutations in the TG gene have been reported. These mutations are transmitted in an autosomal recessive mode.

Two compound heterozygous mutations (c.215delA/c.2422T-->C and c.387delC/c.1159G-->A) in the thyroid peroxidase gene responsible for congenital goitre and iodide organification defect.

Background: Iodide organification defects are frequently but not always associated with mutations in the thyroid peroxidase (TPO) gene and characterized by a positive perchlorate discharge test. These mutations phenotypically produce a congenital goitrous hypothyroidism, with an autosomal recessive mode of inheritance.

Objectives: In the present study we extended our initial molecular studies in six unrelated patients heterozygous for the TPO mutations, in order to identify the second mutation in this autosomal recessive disease.

Congenital hypothyroidism with goitre caused by new mutations in the thyroglobulin gene.

Context: Thyroid dyshormonogenesis is associated with mutations in the thyroglobulin (TG) gene and characterized by normal organification of iodide and low serum TG. These mutations give rise to congenital goitrous hypothyroidism, transmitted in an autosomal recessive mode.

Objectives: The aim of this study was to identify new mutations in the TG gene in an attempt to increase the understanding of the molecular basis of this disorder.

Three mutations (p.Q36H, p.G418fsX482, and g.IVS19-2A>C) in the dual oxidase 2 gene responsible for congenital goiter and iodide organification defect.

Background: Iodide organification defects are associated with mutations in the dual oxidase 2 (DUOX2) gene and are characterized by a positive perchlorate discharge test. These mutations produce a congenital goitrous hypothyroidism, usually transmitted in an autosomal recessive mode.

Methods: We studied the complete coding sequence of the human DUOX2 gene by single-strand conformational polymorphism (SSCP) analysis of DNA from 17 unrelated patients with iodide organification defects.

Efficacy of congenital hypothyroidism neonatal screening in preterms less than 32 weeks of gestational age: more evidence.

Objective: To evaluate the double screening performed for congenital hypothyroidism (CH) to preterm infants <32 weeks of gestational age (GA) between 1994 and 2003.

Infants And Methods: TSH was assessed by IFMA. Infants were classified as: term (T) (>37 weeks GA); preterm (PT) (33-37 weeks GA); and very preterm (VPT) (< or =32 weeks GA).

Neonatal TSH levels as an index of iodine sufficiency: differences related to time of screening sampling and methodology.

Introduction: Current WHO guidelines consider that under adequate iodine intake <3% of newborns should have neonatal TSH levels of >5 mU/l blood when screening is performed in cord blood or at 3 days to 3 weeks of age.

Objective: To estimate whether this absolute criterion when applied to newborns older than 48 h of age and native to Buenos Aires coincides with the traditional ones (goiter and urinary iodine in school-age children (SAC)), and if the evaluation varies with either the methodology used for TSH measurements and/or the time of specimen sampling.

Population And Methods: TSH was measured by an immunofluorometric assay (IFMA) on filter paper blood spots of 186 cord blood samples, 112 babies <48 h of age and 1,500 newborns >48 h of age, and by immunoradiometric assay (IRMA) in 238 newborns.

Pediatric Graves' disease: outcome and treatment.

Unlabelled: Graves' disease treatment in children and adolescents includes antithyroid drugs (ATD), 131I (RI) or subtotal thyroidectomy (CX), all of which present beneficial effects and disadvantages.

Objective: To review our experience in the management of pediatric patients with Graves' disease considering the therapeutic strategies used.

Patients And Methods: Clinical and biochemical data of 116 children (23 boys) aged 11.

The C105fs114X is the prevalent thyrotropin beta-subunit gene mutation in Argentinean patients with congenital central hypothyroidism.

Background: Congenital isolated thyrotropin (TSH) deficiency is an unusual condition characterized by low levels of thyroid hormones and TSH, usually presenting early typical signs of severe hypothyroidism. Five different beta-TSH mutations have been described so far. While 4 of them affect only consanguineous families, a frameshift mutation in exon 3 (C105fs114X) has been found also in nonconsanguineous families.

Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect.

Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine. We analyzed the TPO gene in 14 unrelated patients with clinical evidence of iodide organification defects. Seven of the affected individuals harbored mutations in the TPO gene; one was compound heterozygous, the others were simply heterozygous for TPO mutations.

Congenital secondary hypothyroidism due to a mutation C105Vfs114X thyrotropin-beta mutation: genetic study of five unrelated families from Switzerland and Argentina.

We identified five patients with congenital secondary hypothyroidism with isolated thyrotropin (TSH) deficiency originating from three and two unrelated Argentinean and Swiss families, respectively. The affected patients presented with both low TSH as well as low thyroid hormone levels. Further, TSH-releasing hormone (TRH) stimulation failed to increase serum TSH, whereas prolactin increased adequately.

Neonatal screening program for congenital adrenal hyperplasia: adjustments to the recall protocol.

Objective: To evaluate the influence of gestational age (GA) and birth weight (BW) on 17 alpha-OH-progesterone (17-OHP) levels with respect to their impact on the recall rate of neonatal screening programs for congenital adrenal hyperplasia (CAH).

Patients And Methods: In June 1997 we began a pilot screening program for CAH measuring 17-OHP using a fluoroimmunoassay method (DELFIA) on dried blood spots. Until September 1999, 24,153 babies were screened.