The relationship between body mass index and thyroid cancer pathology features and outcomes: a clinicopathological cohort study.

BACKGROUND: Obesity has been implicated as a predisposing and disease-modifying factor in cancer. Epidemiological studies suggest that obesity is associated with an increased risk of thyroid cancer; however, the relationships between obesity and thyroid cancer stage or behavior are uncertain. We hypothesized that a higher body mass index (BMI) would be associated with aggressive thyroid cancer features and a higher incidence of persistent/recurrent disease. METHODS: Two hundred fifty-nine consecutive patients with thyroid cancer were enrolled in this retrospective cohort study. Histopathological tumor features, stage at diagnosis, and disease status during and at the end of the study were determined based on chart review. BMI was calculated at the first clinical visit to our institution. The relationships between BMI and these parameters were assessed. RESULTS: Mean follow-up time for the group was 6.2 yr (0.11-46 yr). No positive associations were identified between BMI and T, N, or M stage at diagnosis, vascular invasion, or recurrent or persistent disease on univariate or multivariate analyses. The absence of an association was also demonstrated on analysis by BMI quartiles. An unexpected inverse association was identified between BMI and nodal metastasis and tumor invasion on both univariate and multivariate analyses, suggesting that obesity may be associated with less aggressive tumor features, a finding that requires confirmatory studies. CONCLUSION: Although obesity has been associated with increased thyroid cancer incidence, a higher BMI was found not to be associated with more aggressive tumor features or a greater likelihood of recurrence or persistence over the analyzed time period.

CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity.

The chloride intracellular channel 5A (CLIC5A) protein, one of two isoforms produced by the CLIC5 gene, was isolated originally as part of a cytoskeletal protein complex containing ezrin from placental microvilli. Whether CLIC5A functions as a bona fide ion channel is controversial. We reported previously that a CLIC5 transcript is enriched approximately 800-fold in human renal glomeruli relative to most other tissues. Therefore, this study sought to explore CLIC5 expression and function in glomeruli. RT-PCR and Western blots show that CLIC5A is the predominant CLIC5 isoform expressed in glomeruli. Confocal immunofluorescence and immunogold electron microscopy reveal high levels of CLIC5A protein in glomerular endothelial cells and podocytes. In podocytes, CLIC5A localizes to the apical plasma membrane of foot processes, similar to the known distribution of podocalyxin and ezrin. Ezrin and podocalyxin colocalize with CLIC5A in glomeruli, and podocalyxin coimmunoprecipitates with CLIC5A from glomerular lysates. In glomeruli of jitterbug (jbg/jbg) mice, which lack the CLIC5A protein, ezrin and phospho-ERM levels in podocytes are markedly lower than in wild-type mice. Transmission electron microscopy reveals patchy broadening and effacement of podocyte foot processes as well as vacuolization of glomerular endothelial cells. These ultrastructural changes are associated with microalbuminuria at baseline and increased susceptibility to adriamycin-induced glomerular injury compared with wild-type mice. Together, the data suggest that CLIC5A is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. We postulate that the interaction between podocalyxin and subjacent filamentous actin, which requires ezrin, is compromised in podocytes of CLIC5A-deficient mice, leading to dysfunction under unfavorable genetic or environmental conditions.

Acute bacterial suppurative thyroiditis: a clinical review and expert opinion.

BACKGROUND: Acute suppurative thyroiditis (AST) resulting from a bacterial infection is an infrequent but potentially life-threatening endocrine emergency. Traditional management of this disease has been surgery in conjunction with targeted antibiotic therapy. Recent nonrandomized reports of small series have demonstrated good outcomes using less invasive approaches. No randomized clinical trials have been performed. Here, we provide a review of the literature and an approach to this problem based on expert opinion. METHODS: The literature was reviewed utilizing PubMed, and a representative case of AST was presented to a panel of experts. Endocrinology, surgery, and infectious disease experts responded to a series of questions regarding diagnosis, management, prognosis, and harm. RESULTS: Combining a broad spectrum of clinical expertise and the published literature, the authors suggest a clinical algorithm as a guide to management, addressing both diagnosis and acute and long-term management. CONCLUSIONS: Published studies indicate a trend toward less invasive management during active inflammation and infection and regarding definite therapy. Remaining questions are presented to foster an evidence-based approach to this disease. Ideally, future randomized, controlled trials will provide data to improve the therapy and outcome of AST.

Dysregulation of the phosphatidylinositol 3-kinase pathway in thyroid neoplasia.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is an important regulator of many cellular events, including apoptosis, proliferation, and motility. Enhanced activation of this pathway can occur through several mechanisms, such as inactivation of its negative regulator, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and activating mutations and gene amplification of the gene encoding the catalytic subunit of PI3K (PIK3CA). These genetic abnormalities have been particularly associated with follicular thyroid neoplasia and anaplastic thyroid cancer, suggesting an important role for PI3K signaling in these disorders. In this article, the role of PI3K pathway activation in thyroid cancer is discussed, with a focus on recent advances.