Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

Objective: MicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules. Design: In this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA. Methods: The prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed. Results: Using data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules. Conclusions: The expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method.

Subclinical hypothyroidism of chronic autoimmune thyroiditis must be distinguished from the rare condition of thyroid resistance to TSH in which variable degrees of congenital insensitivity of the thyroid to a biologically active TSH molecule are present. We studied 42 subjects with slight to moderate elevations of circulating TSH and normal free thyroid hormone levels in whom the diagnosis of autoimmune thyroid disease had been excluded using the best of the currently available laboratory and instrumental techniques. In three families (A, B, and C), which included 8 of the 42 cases, other members besides the propositus were found to have isolated hyperthyrotropinemia. The entire coding regions of the TSH receptor (TSHr) gene were sequenced, and TSHr mutations were found in five subjects from families A and B. No mutations were identified in the two members of family C, in one member of family A, and in the 34 remaining cases of isolated hyperthyrotropinemia. A previously described P162A mutation was found in the proband (homozygous state), the son, and the mother of family A (both in the heterozygous state). A new inactivating heterozygous mutation was found in the proband and the mother of family B and consisted of the substitution of a leucine in place of a highly conserved proline at position 252 (L252P) in the extracellular portion of the TSHr. After transfection in COS-7 cells, the mutant L252P displayed a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. A structural defect of the mutant TSHr protein was probably responsible for the poor routing of the receptor to the cell membrane. In conclusion, in two of three families, but in none of 34 sporadic cases of isolated hyperthyrotropinemia, inactivating mutations of the TSHr were identified. The question of whether the latter cases represent subtle forms of autoimmune thyroiditis or might bear as yet unidentified genetic defects remains a matter of future studies.

Genetic analysis of the DUOX2 gene was performed in 11 children with organification defect. Two new mutations (Y1150C and A728T) and the deletion S965FsX994 were responsible for the deficit in the organification process and the phenotypes. Three polymorphisms (H678R, P982A, and R701Q) were identified.

To date, this study demonstrates the highest prevalence (29%) of TSHR gene mutations in children and adolescents with non-autoimmune subclinical hypothyroidism not selected by neonatal screening. Functional studies show that some mutations cause a slight inactivation of the TSHR. This reveals a possible limit of the in vitro study or of the knowledge of mechanisms involving TSHR, or that other candidate genes must be considered.

Thyroid hormones have profound effects on mood and behavior, but the molecular basis of thyroid hormone action in the adult brain is relatively unknown. In particular, few thyroid hormone-dependent genes have been identified in the adult brain despite extensive work carried out on the developing brain. In this work we performed global analysis of gene expression in the adult rat striatum in search for genomic changes taking place after administration of T(3) to hypothyroid rats. The hormone was administered in two different schedules: 1) a single, large dose of 25 microg per 100 g body weight (SD) or 2) 1.5 microg per 100 g body weight once daily for 5 d (RD). Twenty-four hours after the single or last of multiple doses, gene expression in the striatum was analyzed using Codelink microarrays. SD caused up-regulation of 149 genes and down-regulation of 88 genes. RD caused up-regulation of 18 genes and down-regulation of one gene. The results were confirmed by hybridization to Affymetrix microarrays and by TaqMan PCR. Among the genes identified are genes involved in circadian regulation and the regulation of signaling pathways in the striatum. These results suggest that thyroid hormone is involved in regulation of striatal physiology at multiple control points. In addition, they may explain the beneficial effects of large doses of thyroid hormone in bipolar disorders.

Biofortification of vegetables with iodine provides a mild but significative increase in UI concentration and, together with the habitual use of iodized salt, may contribute to improve the iodine nutritional status of the population without risks of iodine excess.

Hypocalcemia and hyperphosphatemia because of resistance towards parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder that is caused by GNAS methylation changes, resistance can occur towards other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3-20 years later. Although anti-TPO antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL and A/B, and gain of methylation at exon NESP55, i.e. findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications.