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.

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.

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.

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.

Familial non-medullary thyroid carcinoma (FNMTC): analysis of fPTC/PRN, NMTC1, MNG1 and TCO susceptibility loci and identification of somatic BRAF and RAS mutations.

Linkage analysis has identified four familial non-medullary thyroid carcinoma (FNMTC) susceptibility loci: fPTC/PRN (1p13.2-1q22), NMTC1 (2q21), MNG1 (14q32) and TCO (19p13.2). To date, there is no evidence for the involvement of genes from the RAS/RAF signalling pathway in FNMTC. The aim of our study was to evaluate the role of the four susceptibility loci, and RAS/RAF signalling pathway genes, in FNMTC. In total, 8 FNMTC families, and 27 thyroid lesions from family members (22 papillary thyroid carcinomas (PTCs): 11 classic, 10 of the follicular variant and 1 of the mixed variant; 4 follicular thyroid adenomas (FTAs) and 1 nodular goitre (NG)), were evaluated for the involvement of the four susceptibility regions, using linkage and loss of heterozygosity (LOH) analyses. BRAF and H-, N- and K-RAS mutations were also screened in the 27 lesions and patients. Linkage analysis in seven informative families showed no evidence for the involvement of any of the four candidate regions, supporting a genetic heterogeneity for FNMTC. Twenty tumours (74%), of which 18 were PTCs, showed no LOH at the four susceptibility loci. The remaining seven tumours (four PTCs, two FTAs and one NG) showed variable patterns of LOH. Fourteen tumours (52%) had somatic mutations: BRAF-V600E mutation was observed in 9 out of the 22 PTCs (41%); and H-RAS and N-RAS mutations were detected in 5 out of the 22 PTCs (23%). Our data suggest that the four candidate regions are not frequently involved in FNMTC and that the somatic activation of BRAF and RAS plays a role in FNMTC tumourigenesis.

Treatment of differentiated thyroid carcinoma: a survey.

INTRODUCTION: In January 2005, during the annual meeting of the Portuguese Society of Endocrinology, Diabetes and Metabolism, a questionnaire on the treatment and follow-up of differentiated thyroid carcinoma (DTC) was given to attendants. The aim of this study was to present the survey's results. METHODS: The questionnaire addressed the following issues: the surgical treatment of the gland and cervical lymph nodes, whole body scan and ablation with (131)I, suppression with levothyroxine, and treatment of recurrence and metastases. Fifty-four completed questionnaires were obtained (79% from clinical endocrinologists). RESULTS: When DTC is diagnosed, 67% of respondents reported that total thyroidectomy is always performed. When the diagnosis is made postsurgically, completion of thyroidectomy is recommended by 70% of respondents for papillary carcinoma, by 67% for papillary microcarcinoma and by 44% for minimally invasive follicular carcinoma. Most respondents recommend lymph node dissection if the nodes are involved; 61% systematically perform whole body scan with (131)I after surgery. Twenty-eight percent routinely perform ablation of the thyroid, and 59% request adjuvant radioiodine ablation of the thyroid bed if there is (131)I uptake, if thyroglobulin is increased, or if risk factors are present. The most commonly used ablation dose is 100 mCi. Consensus on the degree of TSH suppression is lacking. Twenty-two percent of the respondents recommend surgery as the first therapeutic option in recurrence and metastases, while 57% prefer (131)I for the treatment of local recurrence. When thyroglobulin levels remain high and the results of (131)I scanning are negative, 50% choose computed tomography scan for the diagnosis of disease recurrence. CONCLUSIONS: The wide variability of responses in this survey and the significant percentage (11 to 41%) of non-responders demonstrates the lack of uniformity in the treatment protocols for DCT in Portugal. According to the published guidelines and the responses to a similar survey performed in Spain, the widest differences are mainly found in lymph node dissection and the treatment of disease recurrence.

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.

Association of polymorphisms in ERCC2 gene with non-familial thyroid cancer risk.

The ERCC2 protein is an evolutionary conserved ATP-dependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp --> Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys --> Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid-type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid-type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results.

Metastatic follicular carcinoma associated with hyperthyroidism.

PURPOSE: A 68-year-old man with metastatic follicular thyroid carcinoma had T3 hyperthyroidism. MATERIAL AND METHODS: A bone scan showed intense uptake in the thyroid and multiple areas of increased uptake in the skeleton. Hyperthyroidism persisted after total thyroidectomy. Treatment with I-131 induced a transient state of euthyroidism lasting approximately 9 months. Further tumor growth and relapse of hyperthyroidism eventually occurred and the patient died 25 months after surgery. Molecular and cytogenetic analyses were performed. RESULTS: No mutations were detected of either of the thyrotropin receptor or of the alpha subunit of the stimulatory guanine-nucleotide-binding proteins. Hyperthyroidism was unlikely the result of thyroid-stimulating receptor antibodies. Comparative genomic hybridization analysis showed that the tumor was characterized by multiple chromosomal imbalances. CONCLUSIONS: This is an unusual case of follicular thyroid carcinoma with initial high I-131 uptake by the thyroid and bone metastases and concurrent hyperthyroidism. Despite the increased I-131 uptake in the tumor, I-131 treatment only transiently controlled the hyperthyroidism and had no effect on tumor size. The cause of hyperthyroidism remained unknown. T3 predominance was unlikely the result of type 2 deiodinase overexpression because loss of genetic material was demonstrated at chromosome 14 long arm, where type 2 deiodinase is mapped.

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.

Follow-up and management of differentiated thyroid carcinoma: a European perspective in clinical practice.

As differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We have proposed, in a previous issue of this Journal, an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. We report here the case of a paradigmatic patient with papillary thyroid carcinoma, with the goal of illustrating the benefits of applying this algorithm in routine clinical practice. We also offer expanded and additional comments on various issues in the management of DTC.