Programmed cell death 4 (PDCD4) as a novel prognostic marker for papillary thyroid carcinoma

Background: The primary goal of papillary thyroid cancer (PTC) management was to stratify patients at pre- and post-surgical level to identify the small proportion of cases with potentially aggressive disease. Purpose: The aim of our study is to evaluate the possible role of programmed cell death 4 (PDCD4) and BRAF status as prognostic markers in PTC. Patients and methods: We investigate programmed cell death 4 (PDCD4) immunohistochemical expression in 125 consecutive PTCs with median follow-up of 75.3 months (range, 15\u201398 months) to verify the possible correlation between BRAF status and correlate the classical clinicopathological prognostic factors and PTC outcome with PDCD4 expression. To further support the data, miR-21 expression was tested (by quantitative real-time PCR and in situ hybridization) in a different series of 30 cases (15 PTCs BRAFwt and 15 PTCs BRAFV600E). Moreover, we validated our results using TGCA thyroid carcinoma dataset. Results: We found that 59.8% of the patients showed low-grade PDCD4 nuclear expression and low-grade expression correlated with BRAF V600E. Compared with BRAF 15 wild-type tissue samples, a significant miR-21 up-regulation was associated with BRAF V600E mutations. Lowgrade PDCD4 resulted, and was associated with aggressive histological variants, higher cancer size, extra-thyroidal extension, multifocality, lymph-node metastasis and lymph nodal ratio at the diagnosis. Concerning the outcome, the low-grade PDCD4 expression correlated at univariate and multivariate analysis, with lower levels of recurrence-free survival rate (RFS) and with poor outcome. Moreover, there was significant association between BRAF V600E patients with PDCD4 nuclear loss and lower RFS, whilet here was significant association between BRAF wild-type patients with PDCD4 nuclear expression and better outcome. Conclusion: These results showed that PDCD4 could predict PTC outcome and that the sum of PDCD4 and BRAF alterations increases the prognostic power of BRAF mutation alone

Prognostic Value of Thyroid Hormone Ratio in Patients With Advanced Metastatic Renal Cell Carcinoma: Results From the Threefour Study (Meet-URO 14)

Background: Thyroid hormone impairment, represented as an alteration in levels of thyroid hormones and a lower fT3/fT4 ratio, has been correlated with a worse prognosis for both cancer and non-cancer patients. The role of baseline thyroid function in patients with metastatic renal cell carcinoma (mRCC) however, has not been studied yet. Materials and Methods: We recorded clinical data, baseline biochemical results, and oncological outcomes from 10 Oncology Units in Italy. We stratified patients into three groups according to the fT3/fT4 ratio value and subsequently analyzed differences in progression-free survival (PFS) and overall survival (OS) in the three groups. We also performed univariate and multivariate analyses to find prognostic factors for PFS and OS. Results: We analyzed 134 patients treated with systemic treatment for mRCC. Median PFS in the low, intermediate, and high fT3/fT4 ratio group were 7.5, 12.1, and 21.7 months respectively (p<0.001); median OS in the three groups were 36.5, 48.6, and 70.5 months respectively (p =0.006). The low fT3/fT4 ratio maintained its prognostic role at the multivariate analysis independently from IMDC and other well-established prognostic factors. The development of iatrogenic hypothyroidism was not associated with a better outcome. Conclusion: We found that baseline thyroid hormone impairment, represented by a low fT3/fT4 ratio, is a strong prognostic factor in patients treated for mRCC in first line setting and is independent of other parameters currently used in clinical practice

The effects of iodine supplementation in pregnancy on iodine status, thyroglobulin levels and thyroid function parameters: Results from a randomized controlled clinical trial in a mild-to-moderate iodine deficiency area

Background: Iodine supplementation during pregnancy in areas with mild-to-moderate iodine deficiency is still debated. Methods: A single-center, randomized, single-blind and placebo-controlled (3:2) trial was conducted. We enrolled 90 women before 12 weeks of gestation. From enrollment up until 8 weeks after delivery, 52 women were given an iodine supplement (225 ug/day, potassium iodide tablets) and 38 were given placebo. At recruitment (T0), in the second (T1) and third trimesters (T2), and 8 weeks after delivery (T3), we measured participants\u2019 urinary iodine-to-creatinine ratio (UI/Creat), thyroid function parameters (thyroglobulin (Tg), TSH, FT3, and FT4), and thyroid volume (TV). The newborns\u2019 urinary iodine concentrations were evaluated in 16 cases. Results: Median UI/Creat at recruitment was 53.3 ug/g. UI/Creat was significantly higher in supplemented women at T1 and T2. Tg levels were lower at T1 and T2 in women with UI/Creat 65 150 ug/g, and in the Iodine group at T2 (p = 0.02). There was a negative correlation between Tg and UI/Creat throughout the study (p = 0.03, r = 120.1268). A lower TSH level was found in the Iodine group at T3 (p = 0.001). TV increased by + 067.43% in the Iodine group, and by + 0611.17% in the Placebo group. No differences were found between the newborns\u2019 TSH levels on screening the two groups. Conclusion: Tg proved a good parameter for measuring iodine intake in our placebo-controlled series. Iodine supplementation did not prove harmful to pregnancy in areas of mild-to-moderate iodine deficiency, with no appreciable harmful effect on thyroid function

Erratum: Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials (European Journal of Clinical Nutrition, (2016), 70, 12, (1354-1359), 10.1038/ejcn.2016.154)

Correction to: European Journal of Clinical Nutrition advance online publication 17 August 2016; doi:10.1038/ejcn.2016.154 Since the publication of this article, the authors have noticed that the author name ‘S Watutantrige-Fernando’ was displayed incorrectly. The PDF and the online versions have been amended

Differentiated Thyroid Carcinoma in Pediatric Age: Genetic and Clinical Scenario

ntroduction: Follicular-derived differentiated thyroid carcinoma (DTC) is the most common endocrine and epithelial malignancy in children. The differences in the clinical and pathological features of pediatric vs. adult DTC could relate to a different genetic profile. Few studies are currently available in this issue, however, and most of them involved a limited number of patients and focused mainly on radiation-exposed populations. Materials and Methods: We considered 59 pediatric patients who underwent surgery for DTC between 2000 and 2017. RET/PTC rearrangement was investigated with fluorescent in situ hybridization and real-time polymerase chain reaction. Sequencing was used to analyze mutations in the BRAF, NRAS, PTEN, PIK3CA genes, and the TERT promoter. The pediatric patients' clinical and molecular features were compared with those of 178 adult patients. Results: In our pediatric sample, male gender and age <15 years coincided with more extensive disease and more frequent lymph node and distant metastases. Compared with adults, the pediatric patients were more likely to have lymph node and distant metastasis, and to need second treatments (p<0.01). In all, 44% of the pediatric patients were found to carry molecular alterations. RET/PTC rearrangement was confirmed as the most frequent genetic alteration in childhood DTC (24.6%) and correlated with aggressive features. BRAFV600E was only identified in 16% of the pediatric DTCs, while NRASQ61R, NRASQ61K, and TERTC250T mutations were very rare. Conclusions: Pediatric DTC is more aggressive at diagnosis and more likely to recur than its adult counterpart. Unlike the adult disease, point mutations have no key genetic role

Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves\u2019 orbitopathy: a small prospective pilot study

PURPOSE: Chronic GC administration has numerous side effects, but little is known about the side effects of their short-term use (<\u20093 months)-particularly, when high doses are involved, as in the treatment of Graves' orbitopathy (GO). We investigated the effects of short-term, high-dose GC on bone turnover markers, bone mineral density (BMD), and trabecular bone scores (TBS). METHODS: Eleven patients (10 females and 1 male; median age 56 years) with active GO who were candidates for treatment with intravenous (iv) methylprednisone were consecutively enrolled. All patients were pretreated with a loading dose of 300,000 units of cholecalciferol, then given a median cumulative dose of 4.5 g (range 1.5-5.25 g) iv methylprednisone. Biochemical parameters of bone metabolism (25OHD3, PTH, P1NP, CTX and bALP) were measured at the baseline, and then 1 week and 1, 3, 6 and 12 months. BMD and TBS were obtained by X-ray absorptiometry (DXA) at the baseline and at 6 and 12 months. On DXA image, morphometric vertebral fracture assessment (VFA) was done. RESULTS: There were no significant changes in PTH, bALP or P1NP. A significant drop in CTX was seen at 1 month (down \u39449.31% from the baseline, p\u2009=\u20090.02), with a return to the baseline at the 3-month measurement. There was a moderate (not significant), but persistent reduction in P1NP. No changes in BMD or TBS came to light. No vertebral fractures were documented. CONCLUSIONS: Short-term, high-dose GC treatment caused a rapid, transient suppression of bone resorption, with no effects on BMD or bone micro-architecture (TBS)

The role of the size in thyroid cancer risk stratification

Only a minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome. Clinical outcomes and molecular aspects were assessed in: 144 DTC 64 40\ua0mm without distant metastases (group 1); 50 DTC > 40\ua0mm without distant metastases (group 2); and 46 DTC with distant metastases (group 3). Group 3 had a worse outcome than the other two groups: during the follow-up, patients more frequently had persistent disease, died, or underwent further treatment. The outcomes did not differ between groups 1 and 2. Group 3 had a higher prevalence of TERT promoter mutations than group 2 (32.6% vs 14%). Group 1 had a higher frequency of BRAF mutations than groups 2 or 3 (61.1% vs 16.0% and 26.1%, respectively), while RAS mutations were more common in group 2 than in groups 1 and 3 (16.0% vs 2.1% and 6.5%, respectively). Groups 1 and 2 shared the same outcome, but were genetically distinct. Only lymph node involvement, distant metastases, older age and (among the molecular markers) TERT promoter mutations were independent predictors of a worse outcome. Metastatic DTC had the worst outcome, while the outcome was identical for large and small non-metastatic DTC, although they showed different molecular patterns. TERT promoter mutations emerged as an independent factor pointing to a poor prognosis

Iodine status from childhood to adulthood in females living in North-East Italy: Iodine deficiency is still an issue

Abstract Purpose: This survey aimed to assess iodine status in a female population at different ages, also investigating their eating habits. Methods: We measured urinary iodine concentrations (UIC) in: 634 females at puberty and 361 fertile women in 246 of whom were considered also their children (134 daughters and 120 sons). All subjects completed a food frequency questionnaire. Results: Median UIC decreased from childhood to adulthood (median UIC 107, 77 and 55 μg/l in the young girls, females at puberty and fertile women, respectively). Though using iodized salt improved iodine status in all groups, a significantly higher UIC was only noted in females at puberty. Milk consumption significantly increased UIC at all ages. In mother–child (both daughters and sons) pairs, the children’s median UIC was nearly twice as high as their mothers’ (UIC 115 vs. 57 μg/l). Milk consumption varied significantly: 56 % of the mothers and 76 % of their children drank milk regularly. The children (both daughters and sons) and mothers who drank milk had UIC ≥100 μg/l in 59 and 34 % of cases, respectively, among the pairs who did not drink milk, 44 % of the children and 19 % of the mothers had UIC ≥100 μg/l. On statistical regression, 3.6 % of the variability in the children’s UIC depended on that of their mothers. Conclusions: Dietary iodine status declines from childhood to adulthood in females due to different eating habits. A mild iodine deficiency emerged in women of child-bearing age that could have consequences during pregnancy and lactation