Maternal Urinary Iodine Concentration during Pregnancy and Its Impact on Child Growth and Neurodevelopment: An 11-Year Follow-Up Study.

Mild-to-moderate iodine deficiency during pregnancy is prevalent worldwide, but its consequences for maternal and child health are not clear. We aimed to investigate the impact of maternal iodine intake during pregnancy on the child's growth and neurodevelopment. This study involved a cohort of 11-year-old children (n = 70) whose mothers had participated in an iodine intake survey during pregnancy. Gestational, neonatal, anthropometric, intelligence quotient (IQ), and socioeconomic parameters were analyzed according to maternal urinary iodine concentration (UIC). There was a positive linear trend of current height Z-score, full-scale IQ, verbal IQ, family income, maternal education, and a negative trend of neonatal TSH levels with increasing maternal UIC levels. However, regression analysis indicated that maternal UIC was not an independent predictor of any gestational, neonatal, or childhood development parameter. Only maternal school education was positively associated with child height and IQ. In conclusion, we did not find any evidence of a direct effect of maternal iodine intake during pregnancy on the long-term growth and neurodevelopment of children. The results suggest that socioeconomic factors are important confounding factors that affect both maternal iodine intake and child development and must be considered when investigating the association between maternal iodine intake and child outcomes.

Iodine Supplementation in Pregnancy in an Iodine-Deficient Region: A Cross-Sectional Survey.

Iodine deficiency is a common problem in pregnant women and may have implications for maternal and child health. Iodine supplementation during pregnancy has been recommended by several scientific societies. We undertook a cross-sectional survey to assess the efficacy of these recommendations in a European iodine-deficient region. Urinary iodine concentrations (UIC) were determined in pregnant women before (n = 203) and after (n = 136) the implementation of guidelines for iodine supplementation in pregnancy. Iodine supplementation (200 µg/day) reduced the proportion of pregnant women with severe iodine deficiency (37.4% to 18.0%, p = 0.0002). The median UIC increased from 67.6 µg/L to 106.8 µg/L but remained below the recommended target level (>150 µg/L) for pregnant women. In conclusion, iodine supplementation in pregnant women improved iodine status in this iodine-deficient region but was insufficient to achieve recommended iodine levels in pregnancy. Additional measures, such as the adjustment of the dose or timing of supplementation, or universal salt iodization, may be needed.

Avidity and Outcomes of Radioiodine Therapy for Distant Metastasis of Distinct Types of Differentiated Thyroid Cancer.

CONTEXT: The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response. OBJECTIVE: This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease. METHODS: A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response. RESULTS: RAIT avidity was independently associated with histology (P < .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (P = .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (P = .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS. CONCLUSION: DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.

Outcomes of Thyrotropin Alfa Versus Levothyroxine Withdrawal-Aided Radioiodine Therapy for Distant Metastasis of Papillary Thyroid Cancer.

Background: Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy (RAIT) in patients with distant metastatic papillary thyroid cancer (PTC). There are only a few studies comparing rhTSH with levothyroxine withdrawal (LTW) in this context. Our main aim was to compare the two methods of RAIT preparation in terms of avidity and structural/biochemical response in distant metastatic PTC. We also intended to evaluate whether the two methods of RAIT preparation represented independent prognostic factors for progression-free survival (PFS) and disease-specific survival (DSS) in this subset of patients. Methods: We performed a retrospective analysis of all patients with PTC treated with RAIT for distant metastatic disease between 2006 and 2018. We included 95 PTC patients-27 (28.4%) had LTW and 68 (71.6%) had rhTSH for RAIT. Results: The two groups presented similar clinicopathological characteristics, except for median age at PTC diagnosis, which was higher in the rhTSH group (p = 0.001), but the median age at first RAIT for distant metastatic disease was not different between the two methods of preparation, 63 years old (interquartile range [IQR] 23) in the LTW group versus 70 (IQR 26.75), p = 0.06. Avidity was similar between the two groups (p = 0.973). Median estimate PFS (p = 0.076) and DSS (p = 0.084) were also similar between LTW and rhTSH. Regarding RAIT-related side effects, only 1 (3.7%) patient and 5 (7.4%) patients in the LTW and rhTSH groups, respectively, reported sialadenitis (p = 0.670). Conclusions: There were no differences between the two methods of RAIT preparation regarding avidity and clinical response. rhTSH may be used as an alternative method of preparation for RAIT in patients with known distant lesions, as it presents similar clinical outcomes to LTW and a good safety profile.

Efficacy of a Salt Iodization Program on Iodine Status and Intakes in Schoolchildren of São Miguel Island, Azores, Portugal.

INTRODUCTION: Iodine is an essential micronutrient and its deficiency can severely impact children's development. In 2012, the Thyroid Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism discovered that the median urinary iodine concentration (mUIC) level in schoolchildren of São Miguel was far too low at 70.9 µg/L. In response, the government implemented a salt iodization program to help normalize levels. This investigation evaluated the efficacy of such an approach. METHODS: Urinary iodine concentration (UIC) was evaluated in 362 schoolchildren from São Miguel using the fast colorimetric method. RESULTS: mUIC was 106.7 µg/L, significantly higher than that observed in 2012 (p < 0.001). Over half (55.5%) of the schoolchildren had a UIC >100 µg/L versus 23.0% in 2012 (p < 0.001). 9.4% of schoolchildren had a UIC <50 µg/L, significantly lower than the 30.6% reported in 2012 (p < 0.001). DISCUSSION/CONCLUSION: Five years after the implementation of the government salt iodization program, the mUIC increased from 70.9 to 106.7 µg/L. This study confirms the efficacy of the adopted measures in schoolchildren population.

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants.

Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.

Anaplastic Thyroid Cancer: Clinical Picture of the Last Two Decades at a Single Oncology Referral Centre and Novel Therapeutic Options.

Anaplastic thyroid cancer (ATC) is a rare tumour but also one of the most lethal malignancies. Therapeutic modalities have usually been limited, but clinical trials with new drugs are now being implemented. The aims of this study were to analyse the clinical presentation, therapeutic modalities and independent prognostic factors for survival. We also reviewed the most recent literature on novel ATC therapies. We performed a retrospective analysis of 79 patients diagnosed between 2000 and 2018. Variables with impact on survival were identified using the Cox proportional-hazard regression model. At presentation, 6.3% had thyroid-confined disease, 30.4% evidenced extrathyroidal extension and 60.8% were already metastatic. Surgery was feasible in 41.8% and radiotherapy was applied to 35.4%, with those receiving >45 Gy having longer estimated survival (p = 0.020). Chemotherapy, either conventional or with tyrosine kinase inhibitors, was performed in 17.7% and 7.6%, respectively. Multimodality therapy with surgery, radiotherapy and chemotherapy/tyrosine kinase inhibitors (TKI) had the greatest impact on disease specific survival (DSS), providing a risk reduction of death of 96.9% (hazard ratio (HR) = 0.031, 0.005-0.210, p < 0.001). We concluded that most of these patients join reference centres at advanced stages of disease and multimodality treatment may offer the best chances for prolonging survival.

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes.

The incidence of thyroid cancer (TC), particularly well-differentiated forms (DTC), has been rising and remains the highest among endocrine malignancies. Although ionizing radiation (IR) is well established on DTC aetiology, other environmental and genetic factors may also be involved. DNA repair single nucleotide polymorphisms (SNPs) could be among the former, helping in explaining the high incidence. To further clarify the role of DNA repair SNPs in DTC susceptibility, we analyzed 36 SNPs in 27 DNA repair genes in a population of 106 DTCs and corresponding controls with the aim of interpreting joint data from previously studied isolated SNPs in DNA repair genes. Significant associations with DTC susceptibility were observed for XRCC3 rs861539, XPC rs2228001, CCNH rs2230641, MSH6 rs1042821 and ERCC5 rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (p < 0.01) were detected on paired SNP analysis, most of which involving CCNH rs2230641 and mismatch repair variants. Overall, a gene-dosage effect between the number of risk genotypes and DTC predisposition was observed. In spite of the volume of data presented, new studies are sought to provide an interpretability of the role of SNPs in DNA repair genes and their combinations in DTC susceptibility.

Poorly Differentiated Thyroid Carcinoma Patients with Detectable Thyroglobulin Levels after Initial Treatment Show an Increase in Mortality and Disease Recurrence.

PURPOSE: The role of thyroglobulin (Tg) in predicting death and recurrence risk in patients with poorly differentiated thyroid carcinoma (PDTC) is not well established. We aimed to analyze Tg levels following total thyroidectomy and adjuvant radioiodine treatment (RAI) in PDTC patients and correlate Tg levels with survival and recurrence. METHODS: A retrospective analysis was conducted on 101 patients with PDTC who were treated between 1986 and 2010. Among them, 38 had no distant metastases at presentation, were managed by total thyroidectomy and adjuvant RAI, and had negative anti-Tg antibodies. An unstimulated Tg level < 1 ng/mL was used as a cut-off point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ2 test. Overall survival, disease-specific survival (DSS), and recurrence-free survival (RFS), stratified by Tg levels, were calculated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Compared to patients with undetectable Tg, cases with detectable Tg had a lower probability of achieving free surgical margins (21.7 vs. 46.7%; p = 0.04), higher node status (73.3 vs. 21.8%; p = 0.005), decreased 5-year DSS (65 vs. 100%; p = 0.009), and worse 5-year RFS (32 vs. 84%, p = 0.010), with a significant number of patients having a recurrence in the first year (50 vs. 12.5%; p = 0.021). Patients with detectable Tg levels also showed worse locoregional (55.6 vs. 90.9%; p = 0.014) and distant control (5-year distant control of 46.9 vs. 91%; p = 0.017). CONCLUSIONS: Our results suggest that detectable Tg levels after surgery and RAI in a subset of PDTC patients appear to predict a higher rate of death and recurrence.

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility.

Thyroid cancer (TC) is the most common endocrine malignancy and its incidence continues to rise worldwide. Ionizing radiation exposure is the best established etiological factor. Heritability is high; however, despite valuable contribution from recent genome-wide association studies, the current understanding of genetic susceptibility to TC remains limited. Several studies suggest that altered function or expression of the DNA mismatch repair (MMR) system may contribute to TC pathogenesis. Therefore, the present study aimed to evaluate the potential role of a panel of MMR single nucleotide polymorphisms (SNPs) on the individual susceptibility to well-differentiated TC (DTC). A case-control study was performed involving 106 DTC patients and 212 age- and gender-matched controls, who were all Caucasian Portuguese. Six SNPs present in distinct MMR genes (MLH1 rs1799977, MSH3 rs26279, MSH4 rs5745325, PMS1 rs5742933, MLH3 rs175080 and MSH6 rs1042821) were genotyped through TaqMan® assays and genotype-associated risk estimates were calculated. An increased risk was observed in MSH6 rs1042821 variant homozygotes [adjusted odds ratio (OR)=3.42, 95% CI: 1.04-11.24, P=0.04, under the co-dominant model; adjusted OR=3.84, 95% CI: 1.18-12.44, P=0.03, under the recessive model]. The association was especially evident for the follicular histotype and female sex. The association was also apparent when MSH6 was analysed in combination with other MMR SNPs such as MSH3 rs26279. Interestingly, two other SNP combinations, both containing the MSH6 heterozygous genotype, were associated with a risk reduction, suggesting a protective effect for these genotype combinations. These data support the idea that MMR SNPs such as MSH6 rs1042821, alone or in combination, may contribute to DTC susceptibility. This is coherent with the limited evidence available. Nevertheless, further studies are needed to validate these findings and to establish the usefulness of these SNPs as genetic susceptibility biomarkers for DTC so that, in the near future, cancer prevention policies may be optimized under a personalized medicine perspective.

Second Primary Cancer in Patients with Differentiated Thyroid Cancer: Does Radioiodine Play a Role?

BACKGROUND: Well-differentiated thyroid cancer (WDTC) is the most common endocrine neoplasia, and its incidence is rising. Studies have reported an increased risk of second primary cancer (SPC) in WDTC survivors, but its relationship with radioiodine treatment (RAIT) and other risk factors remains controversial. This study evaluated whether RAIT is an independent risk factor for SPC in WDTC patients. METHODS: This was a retrospective single-center study. A total of 2031 patients with WDTC diagnosed between 1998 and 2009, treated and followed at the authors' tertiary cancer center, were included. RESULTS: The median age of patients was 48 years (range 5-90 years); 83% were women and 77% underwent RAIT. The median follow-up was 8.8 years (range 5.0-17.0 years). A total of 130 SPC were diagnosed: 108/1570 (6.9%) received RAIT (RAIT+) and 22/461 (4.8%) did not (RAIT-). The most common SPC was breast cancer (31%), followed by genitourinary and gastrointestinal cancer (18% each). The 10-year cumulative incidence of SPC was 8.2% in RAIT+ and 4.5% in RAIT-. The absolute risk increase in the RAIT+ group versus the RAIT- group at 10 years of follow-up was 0.039 [confidence interval (CI) 0.011-0.067] per patient-year. The number needed to harm (NNH) was 25.6 [CI 15.0-87.2], indicating that on average during a 10-year follow-up period, there is one additional case of SPC for every 26 patients receiving RAIT. When controlling for age, sex, and familial and personal histories of cancer, there was an 84% increase in the risk of SPC in the RAIT+ group compared to the RAIT- group (p = 0.026; relative risk = 1.84 [CI 1.02-3.31]). There was an association between SPC incidence and total cumulative activity administered, which was statistically significant >200 mCi. The incidence of SPC was higher in both the WDCT and the RAIT+ cohorts compared to the general population (standardized incidence ratios = 1.32 and 1.40, respectively). CONCLUSION: These results indicate that in spite of the low incidence of SPC in WDTC patients, the risk is increased after RAIT, particularly for activities >200 mCi. Thus, considering the excellent survival of patients with WDTC, clinicians need to weigh the risks and benefits of RAIT, especially in patients with low-risk thyroid cancer.

Retrospective analysis of 140 cases of medullary thyroid carcinoma followed-up in a single institution.

Familial cases of medullary thyroid carcinoma (MTC) may be diagnosed by genetic screening, while in sporadic tumors the diagnosis relies mainly on fine-needle aspiration cytology. The aim of the present study was to determine the demographic, clinical and pathological characteristics of MTC patients followed-up at the Portuguese Institute of Oncology Francisco Gentil (Lisbon, Portugal). For that purpose, a retrospective analysis of 140 MTC patients diagnosed between 1990 and 2010 was performed. The results indicated that patients with hereditary MTC (11.4%) were significantly younger than patients with sporadic MTC. Of the latter, 34.3% had no clinical suspicion of MTC prior to surgery. The sensitivity of cytology and calcitonin (CT) assay in diagnosing MTC were 51.3 and 98.7%, respectively. All familial index cases and 69.0% of sporadic cases presented with advanced stage disease at the time of diagnosis, while 73.0% of familial MTC detected by genetic/pentagastrin screening were diagnosed at the early stage of the disease. Biochemical cure (BC) was achieved in 39.7% of patients and, of these, only 6.5% relapsed. The 5 and 10-year survival rates were 79.3 and 73.6%, respectively. Age >45 years (P=0.026), advanced stage at diagnosis (P<0.001) and absence of BC (P<0.001) were predictors of a worse prognosis on univariate analysis. However, when the patients detected by genetic/pentagastrin screening were excluded from the analysis, age was no longer a prognostic factor, although disease stage remained a significant prognostic factor. On multivariate analysis, BC was the only factor with a significant impact on prognosis (P=0.031). In addition, the present study confirmed that the majority of patients were diagnosed at advanced stages, and CT determination was observed to be more sensitive than cytology to diagnose MTC. Patients at early stages were more prone to achieve BC, which was a favorable prognostic factor. To the best of our knowledge, the present study reports for the first time that age at diagnosis is not a predictor of survival for patients with MTC when cases diagnosed by genetic/pentagastrin screening (who are usually young patients at the initial stages of the disease), are excluded from the analysis.

Review of clinical and pathological features of 93 cases of well-differentiated thyroid carcinoma in pediatric age at the Lisbon Centre of the Portuguese Institute of Oncology between 1964 and 2006.

INTRODUCTION: Thyroid carcinoma is the most common endocrine malignancy. In childhood, thyroid carcinoma usually behaves aggressively and relapses frequently. Nevertheless, it has a favorable prognosis. Our aim is to present our experience with pediatric well-differentiated thyroid carcinoma (WDTC) treated at the Portuguese Institute of Oncology in Lisbon (L-PIO), between 1964 and 2006. METHODS: Review of clinical files of WDTC in≤18-year-old patients selected from the databases of the Endocrinology Service of L-PIO and the South Portugal Regional Cancer Registry (SPCR). RESULTS: 93 cases of WDTC were found. Of these, 70 (75.3%) were girls. The median age was 15 years old (range 5-18) with a median follow-up time of 15.1 years (range 0.2-47.8). The most common histological diagnosis was papillary carcinoma of the classical variant (n=60, 64.5%). Initial staging showed locoregional dissemination in 27 (29.0%) patients and distant metastasis in 16 (17.2%) patients. Median age was lower in patients with distant disease than in patients with locoregional disease or with disease confined to the thyroid (P=0.007). After the initial treatment, 44 (47.3%) patients were in remission and 46 (49.5%) had persistent disease (lost follow-up in 3). Of the disease-free patients after initial treatment, 11 (25.0%) relapsed later. At the last observation, most patients (n=63, 67.7%) showed no evidence of disease. CONCLUSION: Our study demonstrates that children with distant metastatic disease are younger than children with a less aggressive disease. However, in both groups the response to treatment is favorable and the prognosis is usually excellent.

Ability of the rhTSH stimulation test to predict relapse in patients with differentiated thyroid carcinoma, after long-term follow-up.

The analysis of serum thyroglobulin (Tg) following thyroid-stimulating hormone (TSH) stimulation (sTg) has been recommended in the follow-up of differentiated thyroid carcinoma (DTC) patients, however, its routine use remains controversial. The aim of the current study was to evaluate the accuracy of sTg testing following recombinant human (rh) TSH stimulation in DTC patients, with a follow-up of 12.4 years. Retrospective studies were conducted of 125 DTC patients, who underwent rhTSH stimulation testing between 1999 and 2002. The exclusion criteria were: Patients with anti-Tg antibodies, Tg levels >1 ng/ml under TSH suppression and the absence of radioactive iodine (RAI) ablation therapy following surgery. In total, 49 patients were included in the study and all had been previously treated with total or near total thyroidectomy (with or without central neck dissection) and RAI, postoperatively. The Tg functional sensitivity was 1.0 ng/ml. The follow-up for patients was performed annually. During the median follow-up of 12.4 years after the rhTSH stimulation test, nine patients exhibited recurrence (18.4%). Of the nine patients, six exhibited sTg levels >2 ng/ml (positive result) and three exhibited levels <2 ng/ml (negative result). Relapse occurred at a mean of 5.9 years following the rhTSH stimulation test. The positive predictive value and negative predictive value (NPV) of positive sTg were 50 and 91.9%, respectively, with a sensitivity of 66.6% and a specificity of 85.0%. The rhTSH-stimulated Tg levels have a high NPV, allowing the identification of the patients who are free of the tumour. These results are consistent with the previously published data; however, to the best of our knowledge, this is the study with the longest follow-up duration after rhTSH stimulation.

The role of CCNH Val270Ala (rs2230641) and other nucleotide excision repair polymorphisms in individual susceptibility to well-differentiated thyroid cancer.

Well-differentiated thyroid cancer (DTC) is the most common form of thyroid cancer (TC); however, with the exception of radiation exposure, its etiology remains largely unknown. Several single nucleotide polymorphisms (SNPs) have previously been implicated in DTC risk. Nucleotide excision repair (NER) polymorphisms, despite having been associated with cancer risk at other locations, have received little attention in the context of thyroid carcinogenesis. In order to evaluate the role of NER pathway SNPs in DTC susceptibility, we performed a case-control study in 106 Caucasian Portuguese DTC patients and 212 matched controls. rs2230641 (CCNH), rs2972388 (CDK7), rs1805329 (RAD23B), rs3212986 (ERCC1), rs1800067 (ERCC4), rs17655, rs2227869 (ERCC5), rs4253211 and rs2228529 (ERCC6) were genotyped using TaqMan® methodology, while conventional PCR-RFLP was employed for rs2228000 and rs2228001 (XPC). When considering all DTC cases, only rs2230641 (CCNH) was associated with DTC risk; a consistent increase in overall DTC risk was observed for both the heterozygous genotype (OR=1.89, 95% CI=1.14-3.14) and the variant allele carriers (OR=1.79, 95% CI=1.09-2.93). Histological stratification analysis confirmed an identical effect on follicular TC (OR=2.72, 95% CI=1.19-6.22, for heterozygous; OR=2.44, 95% CI=1.07­5.55, for variant allele carriers). Considering papillary TC, the rs2228001 (XPC) variant genotype was associated with increased risk (OR=2.33, 95% CI=1.05-5.16), while a protective effect was observed for rs2227869 (ERCC5) (OR=0.26, 95% CI=0.08­0.90, for heterozygous; OR=0.25, 95% CI=0.07-0.86, for variant allele carriers). No further significant results were observed. Our results suggest that NER polymorphisms such as rs2230641 (CCNH) and, possibly, rs2227869 (ERCC5) and rs2228001 (XPC), may influence DTC susceptibility. However, larger studies are required to confirm these results.

[Iodine and thyroid: what a clinic should know]. / Iodo e tiróide: o que o clínico deve saber.

The World Health Organization considers iodine deficiency as a major worldwide cause of mental and development diseases, estimating that about 13% of the world population is affected by diseases caused by iodine deficiency. Iodine is a trace element necessary for the synthesis of thyroid hormones which, since it cannot be formed by the organism, must be taken regularly with food. Fish and shellfish are generally a good source, because the ocean contains a considerable amount of iodine. On the contrary, plants which grow in iodine-deficient soils are poor in this element, as well as meat and other animal products fed in plants low in iodine. Salt is the best way for iodine supplementation. Cooking the food with iodized salt is a desirable practice because it guarantees the presence of this element. There are also other methods to provide iodine to the general population, such as adding iodine to drinking water or taking supplements of iodine. In pregnancy is recommended iodine supplementation, except in patients with known thyroid disorders. Iodine is an essential component of thyroid hormones (T4 and T3). Inadequate iodine intake leads to inadequate thyroid hormone production. The most important consequences of iodine deficiency, in the general population are goiter and hypothyroidism, and in the severe cases, mental retardation, cretinism and increased neo-natal and infant mortality. The International Council for the Control of Iodine Deficiency Disorders (ICCIDD) formed in 1985, with the only aim of achieving optimal iodine nutrition in the world, in cooperation with UNICEF and WHO. In Portugal, recent studies show significant deficiencies in pregnancy and The Portuguese Society of Endocrinology Diabetes and Metabolism, in partnership with General Directorate of Health, proposed an iodine supplementation during pregnancy with 150-200µg/day.

Polymorphisms in base excision repair genes and thyroid cancer risk.

Thyroid cancer (TC) is the most frequent endocrine malignancy, accounting however for only 1-2% of all human cancers, and the best-established risk factor for TC is radiation exposure, particularly during childhood. Since the BER pathway seems to play an important role in the repair of DNA damage induced by IR and other genotoxicants, we carried out a hospital-based case-control study in order to evaluate the potential modifying role of 6 BER polymorphisms on the individual susceptibility to non-familial TC in 109 TC patients receiving iodine-131, and 217 controls matched for age (± 2 years), gender and ethnicity. Our results do not reveal a significant involvement of XRCC1 Arg194Trp and Arg399Gln, OGG1 Ser326Cys, APEX1 Asp148Glu, MUTYH Gln335His and PARP1 Val762Ala polymorphisms on the individual susceptibility towards TC, mostly in agreement with the limited available evidence. By histological stratification analysis, we observed that the association between the presence of heterozygosity in the MUTYH Gln335His polymorphism and TC risk almost reached significance for the papillary subtype of TC. This was the first time that the putative association between this polymorphism and TC susceptibility was evaluated. However, since the sample size was modest, the possibility of a type I error should not be excluded and this result should, therefore, be interpreted with caution. More in depth studies involving larger populations should be pursued in order to further clarify the potential usefulness of the MUTYH Gln335His genotype as a predictive biomarker of susceptibility to TC and the role of the remaining BER polymorphisms on TC susceptibility.

[Iodine intake in Portuguese school children]. / Aporte do Iodo nas Crianças das Escolas em Portugal.

OBJECTIVE: The aim of the present study was to evaluate iodine intake in portuguese school children in order to inform health authorities of eventual measures to be implemented. INTRODUCTION: Iodine is the key element for thyroid hormone synthesis and its deficiency even mild, as found in other European countries, may have deleterious effects in pregnancy resulting in cognitive problems of offsprings. In Portugal there are no recent data on iodine intake in schoolchildren. POPULATION AND METHODS: 3680 children aged 6-12 years of both sexes, from 78 different schools were studied. Iodine intake was evaluated trough urine iodine (UI) determinations using a colorimetic method. RESULTS: The global median UI value was 105.5 µg/L; the percentage of children with UI <100 µg/L was 47.1%, corresponding to 41% of the studied schools. The percentage of values <50 µg/L was 11.8%. The male gender, the south region of the country and the distribution of milk in school were significantly linked with a higher iodine elimination. DISCUSSION: Our global results point to a borderline/ mildly insufficient iodine intake in the portuguese school population. However 47% of the children had UI under 100 µg /L. The comparison of our results with the available data from 30 years ago, point to a considerable improvement, due to silent prophylaxis. Male gender, geographical area and milk distribution influenced positively iodine intake.The importance of milk has been referred in numerous papers. CONCLUSIONS: The study of UI in the Portuguese school population points to a borderline iodine intake. However, in 47% of children iodine intake was inadequate. Compared with data from the eighties, a considerable increase in iodine elimination was found. Taking into account the potencial deleterious effects of inadequate iodine intake, a global prophylaxis with salt iodization has to be considered.

The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk.

Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair genes have been pointed out as possible factors to cancer predisposition. Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main recognized risk factor for thyroid cancer. However, most of the patients do not show chronic contact with IR and the other factors have non-concordant data. Thus, thyroid cancer could be due to gene variations in association with certain exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end-joining (NHEJ) that comprises several polymorphic genes. We intend to study the role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is scarcity of data on the role of these genes in thyroid cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (109 patients and 217 controls) to estimate the potential role of the XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238Gright curved arrow A, Ex21+338Tright curved arrow C, Ex21-352Cright curved arrow A, Ex21+466Aright curved arrow G) polymorphisms in the individual susceptibility for this disease. The results here reported do not associate these polymorphisms with susceptibility for non-familial thyroid cancer. However, when the data were analyzed according to the type of tumour, significant results for Ku80 Ex21-238Gright curved arrow A and Ex21+466Aright curved arrow G were found for papillary tumours (adjusted OR = 2.281; 95% CI =; 1.063-4.894; P=0.034). Taken together these results suggest that some of these variants in NHEJ genes can contribute to thyroid cancer susceptibility. However, further studies with a larger sample size will be needed to support our results.