Search

ABSTRACT Objective: Patients with pediatric differentiated thyroid carcinoma (DTC) treated with radioiodine (RAI) therapy may experience long-term side effects, such as gonadal dysfunction. Therefore, it is crucial to understand the impact of this therapy on ovarian reserve and future pregnancy rates. Subjects and methods: Retrospective analysis of 64 female DTC survivors of childbearing age to assess the risk of infertility due to RAI performed before the age of 19 years. Results: Thirty-two out of the 64 DTC survivors had a history of at least one pregnancy during follow-up. No significant differences were observed between the cumulative RAI activity, treatment regimens (multiple versus single RAI treatment), age at first treatment, or presence of lymph node or distant metastases. Notably, the group without a history of pregnancy had a younger age at the time of diagnosis and larger tumors. Age at first pregnancy was slightly higher than that in the general population, but no increase in negative maternal or fetal outcomes was observed. Conclusions: The results of this study show little observational evidence suggesting important adverse effects of RAI on fertility or pregnancy outcomes among female survivors of childhood DTC. Still, studies including larger populations are warranted.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4–50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30–1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01–7.81); the level was 1.57 ng/mL (0.01–7.81) after multiple RAI doses and 2.99 ng/mL (0.01–6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39–7.81) than those who received more (1.0 ng/mL, 0.01–6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55–52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians’ preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

ABSTRACT There is increasing interest in ultrasound-guided ablation treatments for thyroid diseases, including benign and malignant ones. Surgeons, radiologists, and endocrinologists carry out these treatments, and various organizations within these specialties have recently released multiple international consensus statements and clinical practice standards. The aim of the present consensus statement is to provide guidance, cohesion, and standardization of best practices for thermal ablation procedures of thyroid nodules. The statement includes the indications for these procedures, preprocedural evaluations, technical aspects of the procedures, posttreatment care, follow-up, complications, and training recommendations. This document was written by a panel of specialists from the Brazilian Society of Interventional Radiology and Endovascular Surgery (SOBRICE), the Brazilian Society of Head and Neck Surgery (SBCCP), and the Brazilian Society of Endocrinology and Metabolism (SBEM). The statement does not aim to provide criteria for assessing the capability of specialists to perform the procedure. Instead, it aims to promote the standardization of best practices to reduce potential adverse outcomes. Additionally, it strives to enhance the delivery of high-quality care and the widespread adoption of these technologies on a national level. The recommendations collectively serve as a guidebook for applying best practices in thyroid ablation.

ABSTRACT The incidence of thyroid cancer is increasing globally, but mortality rates have remained steady. Many patients with thyroid cancer have low-risk, nonmetastatic intrathyroidal tumors smaller than 2 cm. Active surveillance has shown benefits in these patients, but the adoption of this approach remains below standard in Latin America. The purpose of this article is to identify ways to improve the incorporation of active surveillance into clinical practice for patients with low-risk thyroid carcinoma in Latin America, taking into consideration cultural and geographic factors. Current recommendations include three steps involving patient participation. The first step, which consists of the initial clinical examination, has eight factors requiring special attention. Anxiety must be managed while considering individual, disease-related, cognitive, and environmental aspects. Terms like "overdiagnosis", "incidentaloma," and "overtreatment" must be explained to the patient. Implementing precise terminology contributes to adequate disease perception, substantially reducing stress and anxiety. Clarifying the nonprogressive nature of thyroid cancer helps dispel myths surrounding the disease. The second step includes advice about procedures and guidelines for patients who choose active surveillance. Flexible monitoring techniques should be implemented, with regular check-ins scheduled based on patient needs. Reasons for adjusting treatment must be clearly communicated to the patient, and changes in preference regarding active surveillance should be considered in advance. The third step includes assistance during follow-up. Patients must be educated about ultrasound results and receive surgical indications from specialized physicians. The effectiveness of active surveillance can be reinforced by explaining to the patients the dynamics of changes in nodule size using clear and concise visual aids.

Objective: A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease pres entation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influe nce of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors. Design and methods: Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff. Results: Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher ris k of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status. Conclusion: Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

ABSTRACT Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians’ Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II–V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; “berry node picking” is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

ABSTRACT Objective: To evaluate the impact of pregnancy on differentiated thyroid carcinomas (DTC) behavior Subjects and methods: Retrospective study of patients diagnosed with DTC before or during pregnancy and treated with standard therapy. In women diagnosed with DTC before pregnancy, we evaluated the occurrence of progression according to categories of response to therapy based on imaging and non-stimulated thyroglobulin (TG) levels. Results: Of 96 analyzed patients, 76 became pregnant after DTC treatment and 20 were diagnosed with DTC during pregnancy. Among women who became pregnant after a DTC diagnosis, no difference was observed regarding response to therapy before and after pregnancy. Disease progression after pregnancy was documented in six of these patients, while seven of them presented progression before pregnancy but were only treated after delivery. Patients with DTC diagnosed during pregnancy had a higher rate of distant metastases at diagnosis (30%) compared with the patients who became pregnant after DTC diagnosis (9.2%, p = 0.01). Conclusion: Pregnancy had no impact on the natural course of DTC. Disease progression after pregnancy was limited and probably related to more aggressive disease and higher risk stratification at diagnosis. Still, mild disease progression may have occurred asymptomatically in some patients.

Summary: Background: The diagnosis of cancer in Bethesda III/IV thyroid nodules is challenging as fine-needle aspiration (FNA) has limitations, and these cases usually require diagnostic surgery. As approximately 77% of these nodules are not malignant, a diagnostic test accurately identifying benign thyroid nodules can reduce “potentially unnecessary” surgery rates. We have previously reported the development and validation of a microRNA-based thyroid classifier (mir-THYpe) with high sensitivity and specificity, which could be performed directly from FNA smear slides. We sought to evaluate the performance of this test in real-world clinical routine to support clinical decisions and to reduce surgery rates. Methods: We designed a real-world, prospective, multicentre study. Molecular tests were performed with FNA samples prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (patients with no indication for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports. Findings: A total of 435 patients (440 nodules) classified as Bethesda III/IV were followed-up. The rate of avoided surgeries was 52·5% for all surgeries and 74·6% for “potentially unnecessary” surgeries. The test achieved 89·3% sensitivity, 81·65% specificity, 66·2% positive predictive value, and 95% negative predictive value. The test supported 92·3% of clinical decisions. Interpretation: The reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgeries with robust performance and support clinical decision-making. Funding: The São Paulo Research-Foundation (FAPESP) and Onkos.

ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

ABSTRACT Objective: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. Materials and methods: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. Results: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. Conclusion: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology. This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.

ABSTRACT This position statement was prepared to guide endocrinologists on the best approach to managing thyroid disorders during the coronavirus disease (COVID-19) pandemic. The most frequent thyroid hormonal findings in patients with COVID-19, particularly in individuals with severe disease, are similar to those present in the non-thyroidal illness syndrome and require no intervention. Subacute thyroiditis has also been reported during COVID-19 infection. Diagnosis and treatment of hypothyroidism during the COVID-19 pandemic may follow usual practice; however, should avoid frequent laboratory tests in patients with previous controlled disease. Well-controlled hypo and hyperthyroidism are not associated with an increased risk of COVID-19 infection or severity. Newly diagnosed hyperthyroidism during the pandemic should be preferably treated with antithyroid drugs (ATDs), bearing in mind the possibility of rare side effects with these medications, particularly agranulocytosis, which requires immediate intervention. Definitive treatment of hyperthyroidism (radioiodine therapy or surgery) may be considered in those cases that protective protocols can be followed to avoid COVID-19 contamination or once the pandemic is over. In patients with moderate Graves’ ophthalmopathy (GO) not at risk of visual loss, glucocorticoids at immunosuppressive doses should be avoided, while in those with severe GO without COVID-19 and at risk of vision loss, intravenous glucocorticoid is the therapeutic choice. Considering that most of the thyroid cancer cases are low risk and associated with an excellent prognosis, surgical procedures could and should be postponed safely during the pandemic period. Additionally, when indicated, radioiodine therapy could also be safely postponed as long as it is possible.

SUMMARY Most papillary thyroid carcinomas (PTC) harbor excellent prognosis. Although rare, distant metastases normally occur in lungs and/or bones. Here we describe a rare case of pancreatic metastasis presenting with rapid onset cholestatic syndrome. A literature review was also performed. A 73-year-old man with a high risk PTC was submitted to total thyroidectomy (TT) followed by radioiodine therapy. After initial therapy, he persisted with progressive rising serum thyroglobulin levels but with no evidence of structural disease. Recently, the patient presented with a rapid onset and progressive cholestatic syndrome. A 4 cm lesion in pancreas was identified, with echoendoscopy fine-needle aspiration biopsy (FNAB) confirming a pancreatic metastasis from PTC. The patient was submitted to a successful pancreaticoduodenectomy. Pancreatic metastases of PTC are rare and few long-term follow-up data are available to guide management. Fourteen cases were former reported, mean age was 65.7 years-old with mean time between PTC and pancreatic metastasis diagnosis of 7.9 years. Nine of them had another distant metastasis, nine were diagnosed by FNAB and just two received sorafenib.

ABSTRACT Objective: Because serum calcitonin (CT) is a reliable marker of the presence, volume, and extent of disease in medullary thyroid cancer (MTC), both the ATA and NCCN guidelines use the 2-3 month post-operative CT value as the primary response to therapy variable that determines the type and intensity of follow up evaluations. We hypothesized that the calcitonin would nadir to undetectable levels within 1 month of a curative surgical procedure. Subjects and methods: This retrospective review identified 105 patients with hereditary and sporadic MTC who had at least two serial basal CT measurements done in the first three months after primary surgery. Results: When evaluated one year after initial surgery, 42 patients (42/105, 40%) achieved an undetectable basal calcitonin level without additional therapies and 56 patients (56/84, 67%) demonstrated a CEA within the normal reference range. In patients destined to have an undetectable CT as the best response to initial therapy, the calcitonin was undetectable by 1 month after surgery in 97% (41/42 patients). Similarly, in patients destined to have a normalize their CEA, the CEA was within the reference range by 1 month post-operatively in 63% and by 6 months in 98%. By 6 months after curative initial surgery, 100% of patients had achieved a nadir undetectable calcitonin, 98% had reached the CEA nadir, and 97% had achieved normalization of both the calcitonin and CEA. Conclusion: The 1 month CT value is a reliable marker of response to therapy that allows earlier risk stratification than the currently recommended 2-3 month CT measurement.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.”

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Parathyroid carcinoma is an infrequent endocrine malignant neoplasm with an aggressive behavior. Two cases of parathyroid carcinoma are described, one with a late diagnosis after previous surgeries for parathyroid hyperplasia, and the other diagnosed after pathologic fracture. The aim of this article is to make a review on recent parathyroid carcinoma literature and discuss these two illustrating cases. There has not been established any etiology for parathyroid carcinoma and no predisposing factors were identified. Parathyroid carcinoma may occur sporadically or as part of a genetic syndrome. The clinical features of parathyroid carcinoma are similar to benign cases of hyperparathyroidism and the pathologic diagnose is difficult. In the absence of metastatic disease in addition to a similar clinical setting, it can be difficult to distinguish benign and malignant hyperparathyroidism. Parathyroid carcinoma is a rare disease which diagnose can be challenging. Recent advances in immunohistochemical analysis may have helped in histopathologic evaluation, but pre-operative detection relies on imaging exams that may not differentiate malignant from benign hyperparathyroidism. The first surgical approach is paramount for disease control. There is still few effective therapeutic options for recurrent and metastatic disease, and these patients' prognostic status remain poor. Promising results were observed with denosumab and PTH immunization, and they may be a useful therapy for advanced cases in the future, but further investigation is required.

The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET/PTC as a prognostic marker in pediatric PTC is still under investigation. We recently showed that AGK-BRAF fusion is prevalent in young patients (mean 10 years) and associated with specific and aggressive pathological features such as multifocality and lung metastasis. In this pilot study, we report a unique patient harboring three different foci: the first was positive for AGK-BRAF fusion, the second was positive for just RET/PTC3 fusion and the third was negative for both rearrangements. To investigate whether AGK-BRAF and RET/PTC3 are associated with genomic instability and chromatin modifications, we performed quantitative fluorescence in situ hybridization (Q-FISH) of telomere repeats followed by 3D imaging analysis and 3D super-resolution Structured Illumination Microscopy (3D-SIM) to analyze the DNA structure from the foci. We demonstrated in this preliminary study that AGK-BRAF is likely associated with higher levels of telomere-related genomic instability and chromatin remodeling in comparison with RET/PTC3 foci. Our results suggest a progressive disruption in chromatin structure in AGK-BRAF-positive cells, which might explain a more aggressive disease outcome in patients harboring this rearrangement.

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.

BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14). The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p

OBJETIVO: avaliar as características clínicas e laboratoriais de parentes de primeiro grau do sexo masculino de pacientes com diagnóstico confirmado de síndrome de ovários policísticos (SOP) e comparar os achados com um grupo controle sem história familiar de SOP. MÉTODOS: foram selecionados aleatoriamente 28 homens com idade entre 18 e 65 anos que possuíam parentesco de primeiro grau com mulheres diagnosticadas com SOP e 28 controles pareados por idade, cintura e índice de massa corporal (IMC). RESULTADOS: homens com parentesco de 1º grau com mulheres com SOP comparados ao Grupo Controle apresentaram níveis mais elevados de triglicerídeos (189,6±103,1 versus 99,4±37,1; pPURPOSE: to evaluate clinical and laboratory characteristics of first-degree male relatives of patients with a confirmed diagnosis of polycystic ovary syndrome (PCOS) and to compare the findings with a control group with no family history of PCOS. METHODS: we randomly selected 28 male individuals aged 18 to 65 years who were first-degree relatives of women diagnosed with PCOS and 28 controls matched for age, waist and body mass index (BMI). RESULTS: men with 1st degree kinship with women with PCOS had higher levels of triglycerides (189.6±103.1 versus 99.4±37.1, p

Background and Objective. An individualized risk-based approach to the treatment of thyroid cancer is being extensively discussed in the recent literature. However, controversies about the ideal surgical approach remain an important issue with regard to the impact on prognosis and follow-up strategies. This study was designed to describe clinical outcomes in a cohort of low and intermediate risk thyroid cancer patients treated with thyroid lobectomy. Methods. Retrospective review of 70 patients who underwent lobectomy. Results. After a median follow-up of 11 years, 5 patients (5/70, 7.1%) recurred and 5 had a completion for benign lesions, while 60 patients (86%) continued to be observed without evidence for disease recurrence. Suspicious ultrasound findings were significantly more common in patients that had structural disease recurrence (100% versus 4.3%, P

Thyroid cancer in children and adolescents is usually a major concern for physicians, patients, and parents. Controversies regarding the aggressiveness of the clinical presentation and the ideal therapeutic approach remain among the scientific community. The current recommendations and staging systems are based on data generated by studies in adults, and this might lead to overtreating in some cases as well as undertreating in others. Understanding the differences in the biology, clinical course, and outcomes in this population is crucial for therapeutic decisions. This paper evaluates the biology, clinical presentation, recurrences, and overall survival as well as the staging systems in children and adolescents with differentiated thyroid cancer.