Context: Within the last two decades, heterozygous loss-of-function PAX8 mutations have been reported in patients with a wide degree of thyroid gland dysfunction and growth despite the presence of identical mutations. Objectives: To search for PAX8 mutations in a cohort of patients with congenital hypothyroidism (CH) and various types of thyroid gland defects. Design: A cross-sectional study was conducted in a cohort of patients. Setting: The French neonatal screening program was used for recruiting patients. Patients: A total of 118 patients with CH, including 45 with familial and 73 with sporadic diseases, were included in this study. The thyroid gland was normal in 23 patients had hypoplasia, 25 had hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy. Results: We found four different PAX8 mutations (p.R31C, p.R31H, p.R108X, and p.I47T) in ten patients (six patients with CH and four family members), two with sporadic and eight with familial diseases. Imaging studies performed in the index cases showed ectopic thyroid gland (nZ2), hypoplasia (nZ2), eutopic lobar asymmetry (nZ1), and eutopic gland compatible with dyshormonogenesis (nZ1). The previously reported p.R31C and the novel p.I47T PAX8 mutations are devoid of activity. Conclusion: Four different PAX8 mutations were detected in six index patients with CH (ten total subjects). The p.R31C, p.R31H, and p.R108X mutations have been reported. The novel p.I47T PAX8 mutation presented loss of function leading to CH. Thyroid ectopy was observed in two cases of PAX8 (p.R31H) mutation, a finding that has not been reported previously. We observed a high inter-individual and intra-familial variability of the phenotype in PAX8 mutations, underlining that population genetic studies for CH should include patients with various clinical presentations.

Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAF V600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAF V600E and pTERT mutations. Results: We found coexistence of pTERT C228T and BRAF V600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAF V600E positives. There was a significant association between pTERT C228T /BRAF V600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERT C228T /BRAF V600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.

A significant proportion of schoolchildren still have ID or EII in the northeast region of Brazil, emphasizing the importance of committed public policies to address this problem. Socioeconomic factors and the lack of education about nutritional importance of iodine were important influencing factors in the presence of ID in schoolchildren.

We report the ocurrence of a novel nonsynonymous substitution in the HinR of the large N-terminal extracellular domain of the TSHR gene in a patient with thyroid hypoplasia. In contrast with four others in whom TSHR mutations of the hinge portion were previously identified, the p.S304R TSHR variation neither affected TSH binding nor cAMP pathway activation. This TSHR gene variant was documented in a CH patient, but the current data do not support its role in the clinical phenotype.