Germline Mutations in Familial Papillary Thyroid Cancer.

Thyroid cancer, predominantly of papillary histology (PTC), is a common cancer mostly diagnosed sporadically. Hereditary PTC is encountered in ~ 5% of cases and may present at an earlier age, with greater risks of metastasis and recurrence, compared with sporadic cases. The molecular basis of hereditary PTC is unknown in most cases.

Long-term remission of disseminated parathyroid cancer following immunotherapy.

Purpose: Parathyroid cancer is a rare tumor associated with poor prognosis particularly when disseminated. While chemotherapy and/or radiotherapy are of no clinical value in disseminated disease, immunotherapy should be considered.

Subject And Results: A patient with CDC73-associated metastatic parathyroid carcinoma was treated with combined anti-hPTH immunotherapy and surgery.

Obesity, Bariatric Surgery, and Vitamin D.

The high prevalence of obesity is a worldwide problem associated with multiple comorbidities, including cardiovascular diseases. Vitamin D deficiency with secondary hyperparathyroidism is common in obese individuals and can be aggravated after bariatric surgery. Moreover, there is no consensus on the optimal supplementation dose of vitamin D in postbariatric surgical patients.

Malignant phenotype and two SDHD mutations in a family with paraganglioma syndrome type 1.

Background: Paraganglioma syndrome type 1 (PGL1) is a rare autosomal dominant syndrome associated with multiple, overwhelmingly benign, pheochromocytomas and paragangliomas, attributed to SDHD gene mutations.

Objective: Clinically and molecularly characterize a family with uncommon malignant phenotype of paragangliomas attributed to two seemingly pathogenic SDHD germline mutations.

Materials & Methods: The proband presented with large bilateral carotid body tumours and family history of cervical masses in his five siblings.

Trabecular bone score (TBS)--a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism.

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture.

The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals.

Background: Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported.

Serum and salivary cortisol in the diagnosis of adrenal insufficiency and as a predictor of the outcome in patients with severe sepsis.

Objectives: To compare salivary with serum total cortisol in patients with severe sepsis, postoperative patients and healthy controls.

Materials And Methods: Serum total cortisol was determined by chemiluminescence immunoassay; salivary cortisol was determined by enzyme immunoassay.

Results: In patients with severe sepsis, median concentration of salivary cortisol was 14.

Papillary thyroid carcinoma with brain metastases: an unusual 10-year-survival case.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with indolent clinical course and good prognosis. Brain metastases are extremely rare and the average survival time after diagnosis has been reported to be around 12 months.

Summary: We here report a 69-year-old patient who was admitted to the emergency room in January 2000 with progressive dizziness, headache, and vomiting.

HRPT2-related familial isolated hyperparathyroidism: could molecular studies direct the surgical approach?

It is still debatable which is the best management to familial forms of hyperparathyroidism. Conservative, minimally invasive or aggressive surgical approaches have been proposed from different groups around the world. Our objective was to study the gene mutation, expression of HRPT2 and the clinical outcome after 32 years of follow-up in one Brazilian kindred with familial isolated hyperparathyroidism (FIHP).

Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations.

Background: Familial forms of hyperparathyroidism are responsible for approximately 10% of the cases of primary hyperparathyroidism, and their management is different from the sporadic forms. Our objective was to study the gene sequence and expression of HRPT2 and clinical outcome regarding recurrence or persistence rates in three Brazilian kindreds with familial hyperparathyroidism after up to 30 years of follow-up.

Methods: Clinical and biochemical data, direct sequencing of germline DNA of the HRPT2 gene, and analysis of parafibromin expression (HRPT2 gene product) using RT-PCR and immunohistochemistry of resected parathyroid neoplasms were performed.

Association between decreased WWOX protein expression and thyroid cancer development.

Context: Chromosomal fragile sites are often related to cancer development. The WW domain-containing oxidoreductase gene (WWOX) spans the second most common chromosomal fragile site (FRA16D) and encodes an important proapoptotic protein.

Objective: To verify our hypothesis that underexpression of WWOX could contribute to malignant transformation of the thyroid cells.

Distinct expression profiles for PTEN transcript and its splice variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.

Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS) are autosomal dominant hamartoma syndromes. Germline PTEN mutations have been associated with 85% of CS cases and 65% of BRRS cases and also with other disorders, which are collectively referred to as the "PTEN hamartoma tumor syndrome." The human PTEN gene has been previously found to express two naturally occurring splice variants (SVs).

High frequency of loss of heterozygosity in imprinted, compared with nonimprinted, genomic regions in follicular thyroid carcinomas and atypical adenomas.

Context: Many mammalian genes that are imprinted regulate cell growth, differentiation, and apoptosis. Because imprinting silences one of the two alleles, resulting in functional haploinsufficiency, we hypothesized that loss of heterozygosity (LOH) at an imprinted locus may result in the deletion of the only functional copy of an imprinted tumor suppressor gene.

Objective: The goal of this study was to specifically address this hypothesis that in thyroid neoplasias loss of imprinted loci becomes enriched during oncogenesis.

Duplication of the hypophysis associated with precocious puberty: presentation of two cases and review of pituitary embryogenesis.

Pituitary duplication is a rare malformation commonly associated with other major neural/craniofacial anomalies, easily shown by magnetic resonance imaging. The authors describe two girls with duplication of the pituitary gland and thickening of the hypothalamus, facial dysmorphism and precocious pubertal development. The pathogenesis of pituitary duplication and its relationship with precocious pubertal development are discussed.

Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma.

More than 30% of adrenal pheochromocytomas are hereditary. These neuroendocrine tumors are major components of three inherited cancer syndromes: multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and pheochromocytoma/paraganglioma syndrome (PC/PGL). Germline mutations in RET; VHL; and SDHB, SDHC, and SDHD are associated with multiple endocrine neoplasia type 2, VHL, and PC/PGL, respectively.