We described a novel mutation in the 5'-untranslated region of the NIS gene in a newborn with congenital hypothyroidism bearing a clinical ITD phenotype. Functional evaluation of the molecular mechanism responsible for impaired NIS-mediated iodide concentration in thyroid cells indicated that the identified mutation reduces NIS translation efficiency with a subsequent decrease in protein expression and function.

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Children born small for gestational age (SGA) are prone to developing obesity, insulin resistance and type 2 diabetes. Adiponectin and leptin are adipocytokines associated with insulin sensitivity parameters. We aimed to relate serum adiponectin and leptin levels with insulin sensitivity parameters in prepuberal SGA children with and without catch-up growth (SGA+CUG; SGA-CUG, respectively) and to analyze the usefulness of these adipocytokines as early markers of insulin resistance. We analysed adiponectin, proinsulin, leptin, growth factors, insulin, HOMA IR and HOMA βcell in 23 SGA+CUG, 26 SGA-CUG children compared with 48 prepuberal appropiate for gestational age (AGA). SGA children had adiponectin levels comparable to AGA children. Leptin levels were different between sexes, showed to be higher in SGA+CUG group (p=0.040) and these were significantly correlated with insulin sensitivity parameters. These results suggest leptin resistance as an adaptive mechanism to increase energy balance, but an altered functional response of adipocytes cannot be discarded. KEY WORDSsmall for gestational age children, insulin sensitivity, adiponectin, leptin

Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.

Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.

GH treatment reduced TR expression in PBMC and biochemical serum markers of TH action. These results suggest that GH treatment in TS patients impair peripheral TH action at tissue level and prompt a role in the reduced growth response to the therapy.

Few reports have addressed normal serum thyroglobulin (Tg) values in newborns and infants. In the present study, serum Tg was measured in 228 normal children (110 females and 118 males) aged from 3 to 180 days of life, all presenting normal age-related serum thyrotropin (thyroid-stimulating hormone [TSH]) values and negative anti-Tg and antithyroperoxidase antibodies. Serum Tg was measured by Radioimmunoassay (RIA) (two methods) and Immunometricassay (IMA) (three methods). Mean Tg values measured by the five methods exhibited among-method biases, although a significant positive correlation was observed. Serum Tg levels measured by the five methods showed a correlation with age, but not with TSH or gender. During the first days of life, relatively high mean Tg levels were observed, which progressively decreased until they reached a plateau. Therefore, with the aim of establishing reference values, the population was separated into two age groups: from 3 to 15 days of life (group A) and from 16 to 180 days of life (group B). Mean Tg concentration in group A was statistically higher than in group B. Tg centile distributions were calculated with the aim of establishing the normal levels of serum Tg for each method. We conclude that for a correct interpretation of serum Tg levels, the age and the methods used should be considered.

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