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Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy – n = 4) and drug therapy problems four (dosage too low – n = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.

Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is a palliative therapeutic option for advanced Neuroendocrine Tumors (NETs). Prognostic factors can predict long-term outcomes and determine response to therapy. Among those already explored, biomarkers from full blood count, including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) has shown value for other solid tumors and for NETs patients submitted to other forms of therapy. However, its relation to PRRT response and patients' prognosis is still to be determined.Medical records from 96 patients submitted to PRRT between 2010 and 2017 were reviewed, median NLR and PLR were calculated from baseline flood blood count and dichotomized as high or low. Progression-free survival (PFS) and Overall Survival (OS) were calculated.NLR and PLR median values were 1.8 and 123, respectively. Patients with low NLR had a significantly longer OS (estimated median of 77.5 months, 95% CI: 27.3-127.7) when compared to patients with high NLR (estimated median of 47.7 months, 95% CI: 34.7-60.8); p = 0.04. Patients with low NLR had a trend toward a longer median PFS when compared to patients with high NLR [estimated medians of 77 months (95% CI: 27.3-127.7), and 47.7 months, (95% CI: 34.7-60.7)], respectively, p = 0.08.Patients with advanced-stage NET with NLR higher than 1.8 have worse long term clinical outcomes after PPRT. Larger studies are needed to validate the optimal cutoff for this biomarker.

Objective A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation 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 influence 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 risk 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.

The purpose of this study was to access changes in health-related quality of life (HRQoL) caused by radioiodine therapy (RAI) in thyroid cancer patients. Prospective cohort study at Brazilian National Cancer Institute with patients enrolled between March 2015 and June 2017. RAI was performed by administration of 1.11 to 9.25 GBq of Na131I. EORTC QLQ-C30 v3 and EORTC QLQ-H&N35 questionnaires were applied to determine HRQoL at baseline, 1 week and 3 months after RAI. HRQoL during follow-up was evaluated by calculation of score absolute changes in each domain. Descriptive analysis was performed by measures of central tendency and dispersion. Changes in HRQoL were evaluated by paired t-test. The association between social demographic and clinical data and HRQoL was assessed by univariate linear regression for significantly changed domains, and p

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients.Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease.Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW.Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve).Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence.

Background: Low risk thyroid cancer can be treated with lobectomy or total thyroidectomy. Studies have shown that the risk of recurrence does not differ between the two surgeries, although there are higher rates of complications with total thyroidectomy. Our study aimed to find if there were differences in quality of life and thyroid function in the two treatments. Methods: Low risk DTC survivors answered three QoL questionnaires (EQ5D3L, SF36, and EORTC QLQ C30) and had their thyroid function evaluated. Results: Twenty-six lobectomy patients and 101 total thyroidectomy were included. Hypoparathyroidism occurred more in the total thyroidectomy, and TSH was more likely to be on target (0.5-2.0) in lobectomy. There was no difference between groups regarding QoL, but there was a significant difference regarding thyroid function. In SF36 form, TSH off target led to more physical limitations, pain, less vitality, and worse social aspects. Abnormal total T3 level was associated with pain, less vitality, and worse mental health. In the EORTC QLQ C30, off target TSH led to worse role functioning, fatigue, and nausea. EQ5D form showed that worse utility index was found when TT3 was not in normal range. Conclusion: This study showed there was a difference among thyroid function, specially TSH depending on type of surgery. When uncontrolled, TSH was associated with worse aspects of the quality of life. Therefore, lobectomy patients have a better thyroid function control and less surgical complications which might have an impact in some aspects of the quality of life when compared to total thyroidectomy.

Around 10–27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6–12 months after RAI ablative dose, at 6–18 months after negative dxWBS and last follow-up visits. Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

BackgroundThe diagnosis of cancer in thyroid nodules with indeterminate cytology (Bethesda III/IV) is challenging as fine-needle aspiration (FNA), the gold standard method, 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 surgery rates. We have previously reported the development and validation of a microRNA-based thyroid molecular classifier for precision endocrinology (mir-THYpe) with high sensitivity and specificity, which could be performed directly from readily available cytological smear slides without the need for a new dedicated FNA. We sought to evaluate whether the use of this test in real-world clinical routine can reduce the rates of surgeries for Bethesda III/IV thyroid nodules and analyze the test performance.MethodsWe designed a real-world, prospective, multicenter cohort study. Molecular tests were performed in a real-world clinical routine with samples (FNA smear slides) prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (for those patients not recommended for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports.ResultsAfter applying the exclusion criteria, 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. After the statistical treatment of non-resected test-negative samples, the test achieved 89.3% sensitivity (95% CI 82–94.3), 81.65% specificity (95% CI 76.6–86), 66.2% positive predictive value (95% CI 60.3–71.7), and 95% negative predictive value (95% CI 91.7–97) at 28.7% (95% CI 24.3–33.5) cancer prevalence. The test influenced 92.3% of clinical decisions.ConclusionsThe reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgery with robust performance and significantly influence clinical decision-making.

Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. Analysis of the presence of TERTp (−124C > T and −146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient’s outcomes. Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5–360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

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.

The incidence of pediatric differentiated thyroid carcinoma (DTC) has been rising in recent years, and the main risk factors for recurrence are lymph node and distant metastasis at diagnosis. Other clinical features remain unclear, such as the impact of age, sex, and puberty. Furthermore, until now, this population has been treated using the same strategies used to treat adults. In 2015, the American Thyroid Association (ATA) published the first guidelines targeted at this age group. The aims of this study were to investigate the prognostic factors for early and long-term remission and also to validate the ATA risk stratification proposal in a population outside the United States.Clinical records from 118 patients18 years old followed in two referral centers were reviewed. The median age was 12 years (range 4-18 years), and 20.3% (24 patients) were10 years old at diagnosis. The median follow-up was 9.1 years. The majority were female (72%) and received total thyroidectomy and radioiodine therapy (RAI), and 61.8% were treated with more than one dose of RAI. The majority were classified as high risk (48.3%) by the new ATA pediatric guidelines due to distant metastasis (30 patients) or extensive lymph node involvement (27 patients). The remained were classified as low risk (31.3%) and intermediate risk (20.4%).Females with no lymph node or distant metastasis and low ATA pediatric risk were more likely to have no evidence of disease (p 0.05) within the first year and also in the long term. In this study, age did not significantly predict outcomes. Furthermore, patients also benefitted from multiple doses of RAI, but when the cumulative activity was400 mCi, this benefit was diminished.This study shows that the ATA risk stratification proposal for pediatric patients is useful in predicting early and long-term outcomes in pediatric patients with DTC. In addition, it shows that sex and metastatic disease are important prognostic factors in pediatric populations.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

SummaryObjective We aimed to determine outcome predictors of papillary thyroid cancer (PTC) persistence and recurrence, separately. Context The factors contributing to either persistence or recurrence of PTC are poorly defined, as both outcomes are usually evaluated together. Design and patients In this 10-year follow-up cohort study, 190 PTC patients were evaluated (18–85 years old; registered from 1 January 1990 to31 December 1999 at a Brazilian Cancer Care referral Hospital). After initial surgery, we examined persistence (disease detected up to 1 year), recurrence (disease detected after 1 year) and PTC-free status (disease absence during follow-up). Measurements Outcome predictors were modelled using multinomial logit regression analysis. Results The univariate analysis showed that persistence and recurrence were significantly associated with lymph node metastasis (OR = 12·33; OR = 2·84, respectively), local aggressiveness (OR = 5·22; OR = 3·35) and extrathyroidal extension (OR = 5·07; OR = 7·11). Persistence was associated with male sex (OR = 3·49), age above 45 years old at diagnosis (OR = 1·03), macroscopic lymph node metastasis (OR = 5·85), local aggressiveness (OR = 5·22), each 1-cm tumour size increase (OR = 1·34), a cancer care referral hospital as the place of initial surgery (OR = 2·3), thyroidectomy or near total thyroidectomy(OR = 3·03) and neck dissection (OR = 3·19). Recurrence was associated with the time of radioactive iodine (131I) therapy (OR = 3·71). After data modelling, persistence was associated with macroscopic lymph node metastasis (OR = 6·17), 1-cm increases in tumour size (OR = 1·30) and thyroidectomy or near total thyroidectomy (OR = 3·82), while recurrence was associated with surgery at referral hospital (OR = 3·79). Conclusions The best predictors of persistence were tumour size and macroscopic lymph node metastasis; when the initial surgery is of quality, the recurrence depends more on tumour's biology aspects.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare disease, and its classic tumor marker is calcitonin. However, recently, very aggressive cases have been reported to also secrete carbohydrate antigen 19-9 (CA19-9), and its role as a marker of worse prognosis has been questioned. The aim of this study was to analyze the relationship between CA19-9 serum levels and MTC outcomes. METHODS: We retrospectively reviewed 122 MTC patients followed in a tertiary cancer center from 1985 to 2017. Clinical-pathologic characteristics, therapeutic approaches, and outcomes were recorded and CA19-9 was collected. RESULTS: Of the 122 patients included in the study, 48 had distant metastases, and at the end of follow-up 18.1% had structural persistent disease and 32.7% had progressive disease. CA19-9 was significantly higher in those who had disease progression than in those who had not (21.4 [14.3–110.9] vs. 7.27 [0.6–44.75] U/mL, p = 0.01) and was also higher in patients who died from MTC (18.4 [14.3–110.9] vs. 7.59 [0.6–67.8] U/mL, p < 0.001). Furthermore, using a ROC curve analysis, the cutoff point for CA19-9 in MTC patients was lower than that observed in pancreatic tumors. CONCLUSION: CA19-9 might have a role as a prognostic factor in addition to calcitonin and carcinoembryonic antigen in metastatic MTC.

OBJECTIVE: Bone metastases bring greater morbi-mortality to patients with differentiated thyroid carcinoma (DTC). Treatment was limited to radioactive iodine (RAI) and local approaches. Currently, bisphosphonates are included in the therapeutic arsenal. The aim of this study is to evaluate the impact of bone metastases and their treatment with zoledronic acid (ZA) and RAI therapy. METHODS: We retrospectively review 50 DTC patients with structurally evident bone metastases followed in a tertiary cancer center from 1994 to 2018. Clinical-pathologic characteristics, skeletal related events (SRE), and therapeutic approaches were recorded. RESULTS: Among the 50 patients analyzed, 22 underwent ZA adjuvant therapy and 28 did not. Mortality rate was 44%. Those patients presented SREs more frequently (90.9 vs. 67.9% the survival group, p = 0.05) and also had a greater number of bone lesions (40.9 vs. 10.7% had more than 6 metastatic sites, p = 0.03). The same group of patients was analyzed before and after therapy with ZA and the incidence of SRE decreased from 1.81 (0–8) before therapy to 0.29 (0–7) after therapy (p = 0.006). Comparing similar groups of 22 patients treated with ZA with 28 patients not treated, there was a trend of better overall survival (OS) in the group that received this drug (147 vs. 119 months, p = 0.06) and significantly improvement when bone metastases were RAI avid 155 (125–185) versus 120 (85–157) months, p < 0.01. Conclusion: ZA can successfully diminish the chance of having new SRE and possibly affect OS in DTC patients with bone metastases. The positive impact of RAI adjuvant treatment on OS is directly associated with RAI uptake.

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.

Objective: The aim of this study was to evaluate the association between this characteristic and outcomes in patients with lymph node metastasis in a Brazilian cohort. Subjects and methods: This study examined a retrospective cohort of adult patients diagnosed with differentiated thyroid cancer and lymph node metastases from 1998 to 2015 in two referral centers. Number, location, size and extranodal extension (ENE) of metastatic lymph nodes were assessed and correlated with response to initial therapy. Results: A greater number of metastatic nodes, larger size, presence of lateral neck disease and ENE were all associated with a lower probability of achieving an excellent response to initial therapy (p ≤ 0.05 for all these parameters). Local recurrent disease had a significant association with lymph node number (6 in the recurrence/persistence group versus 4 in the non-recurrent group; p = 0.02) and ENE (19.2 versus 75%, p = 0.03). Lateral neck disease was the only characteristic associated with distant metastasis and was present in 52.1% of the group without metastasis and 70.4% of the group with metastasis (p = 0.001). Conclusion: The lymph node characteristics were associated with response to initial therapy and neck recurrence/persistence, confirming the importance of the analysis of these factors in risk stratification in a Brazilian population and its possible use to tailor initial staging and long term follow-up.

BackgroundIn most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality.MethodsA cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable.ResultsIn the MSKCC cohort, with a median follow-up time of 54 months (range 1-332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (70 years) showed a 37-fold increase in hazard ratio from age 70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%.ConclusionsMortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome.

Bone mineral density (BMD) seems not to be decreased in young patients given long-term suppressive doses of levothyroxine (LT4), but information regarding the bone microstructure in these patients is lacking. The aim of this study was to determine whether supraphysiologic doses of LT4, initiated during childhood or adolescence for treatment of differentiated thyroid carcinoma (DTC), have any detrimental effects on bone microarchitecture as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Seventeen patients (27.3 ± 7.1 years old) with DTC with subclinical hyperthyroidism since adolescence and 34 healthy volunteers matched for age, sex, and body mass index were studied by dual-energy X-ray absorptiometry (DXA) to determine the areal BMD at the lumbar spine, hip, and proximal third of the radius. Volumetric BMD and structural parameters of the trabecular and cortical bone were assessed by HR-pQCT of the distal radius and distal tibia. DTC patients were given suppressive doses of LT4 starting at a mean age of 12.6 years, and the mean duration of treatment was 14.2 years. In DTC patients, clinical parameters did not correlate with DXA or HR-pQCT parameters. No differences were found between the patients and controls with respect to BMD and Z scores at any site evaluated by DXA, and no differences were found in the bone microstructure parameters evaluated by HR-pQCT. This cross-sectional study suggests that long-standing suppressive therapy with LT4 during the attainment of peak bone mass may have no significant adverse effects on bone density or microarchitecture.

Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC.The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC.Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment.Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy.Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.

Medullary thyroid carcinoma (MTC) is a malignant neoplasm of parafollicular cells. Because it is a neuroendocrine tumor, it has known somatostatin receptors (SSTRs). The actual frequencies of the SSTR subtypes and their potential influences (by binding with endogenous somatostatin) on MTC cell proliferation have not been fully elucidated to date. The present study evaluated the occurrence of SSTR subtypes 1, 2, 3 and 5 as well as the possible role that each subtype plays in the clinical evolution of patients with MTC. This retrospective, longitudinal study analyzed thyroid surgical material from 42 patients with MTC. Immunohistochemical staining was performed with monoclonal antibodies against subtypes 1, 2, 3 and 5 of SSTR. The histological material was classified as negative, focal positive or diffuse positive, in relation to each of the SSTR subtypes. The initial response to treatment, clinical course and patient mortality rate were assessed and related to the presence of SSTR subtypes. The most prevalent SSTR subtype was SSTR 3, which was found in 81% of the patients, when considering any pattern of positivity. However, subtype 2 had the lowest number of positive patients, with 28.6% demonstrating any positive pattern. Subtypes 1 and 5 had an intermediate prevalence of positivity, with subtype 1 present in 45.2% of the patients and subtype 5 positive in 54.8% of the patients, when considering any pattern of positivity. The presence of STR 1, in the form of diffuse positivity, independently predicted a better response to the initial therapy, with a hazard ratio (HR) of 4.80 (p = 0.03). This is the first study to show the correlation of the presence of SSTR1, detected by monoclonal immunohistochemical techniques, and better response to initial treatment and possibly better long-term clinical response in patients with MTC. In addition, these patients had low positivity rates for SSTR2, which might explain the low sensitivity of diagnostic and limited therapeutic response to octrotide based radioisotopes.

Management of small well-differentiated thyroid cancer (DTC) has generated much debate regarding the surgical approach and radioactive iodine treatment (RAI).The aim of the study was to evaluate the impact of surgical extension and RAI on the outcome of DTC ≤2 cm.A retrospective analysis of 176 cases of DTC ≤2 cm was performed.At diagnosis, tumor size was 1.38 ± 0.55 cm, age 40.2 ± 13.6 years. After a mean follow-up period of 14.1 ± 4.5 years, 15.9 % patients had recurrent/persistent structural disease, with cervical neck disease (thyroid gland area and/or cervical lymph nodes) in 11.9 % cases and distant metastasis in 5.1 %. Disease specific mortality was of 1.1 %. No difference in outcome was observed between patients submitted to total or subtotal thyroidectomy. After total and subtotal thyroidectomy, the rate of recurrent/persistent structural disease was 19.1 and 10.6 % (p = 1.00), respectively. Using the multivariate cox proportion hazards analysis, no difference in the clinical outcome was observed after total or subtotal thyroidectomy (p = 0.703) neither after RAI (p = 0.807). Similar results were observed after stratification by tumor size. Multifocal disease (p = 0.007), extra-thyroid extension (p = 0.007) and presence of lymph node metastasis (p = 0.000) were associated with unfavorable outcome.Total thyroidectomy and RAI did not improve clinical outcomes of DTC ≤2.0 cm when compared with less extensive surgery and no RAI in selected patients. Therefore, in carefully selected patients with DTC ≤2.0 cm and no unfavorable risk factors (multifocal disease, extra-thyroid extension, lymph node and/or distant metastasis), less extensive surgery and no RAI may be acceptable treatment options.

PURPOSE OF THE REPORT The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. PATIENTS AND METHODS This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. RESULTS During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. CONCLUSION Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).

AMP-activated protein kinase (AMPK) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism and cell survival. Recently, our group described that AMPK plays an important role in the regulation of iodide and glucose uptake in thyroid cells. However, AMPK signaling pathway in human thyroid carcinomas has not been investigated so far.ObjectiveTo evaluate the expression and activity of AMPK in papillary thyroid carcinomas.MethodsWe examined total and phosphorylated AMPK (tAMPK and pAMPK) and phosphorylated acetyl-CoA-carboxylase (pACC) expressions through imunohistochemistry, using a tissue microarray block composed of 73 papillary thyroid carcinomas (PAP CA) or microcarcinomas (PAP MCA) and six adenoma (AD) samples from patients followed at the Federal University Hospital. The expression levels were compared with the non-neoplastic tissues from the same patient. Two different pathologists analyzed the samples and attributed scores of staining intensity and the proportion of stained cells. A total index was obtained by multiplying the values of intensity and the proportion of stained cells (INTxPROP).ResultstAMPK, pAMPK, and pACC showed a predominant cytoplasmic staining in papillary carcinomas, adenomas, and non-neoplastic thyroid tissues. However, the intensity and the proportion of stained cells were higher in carcinomas, so that a significant increase was found in the INTxPROP score both in PAP CA and PAP MCA, when compared with their respective controls.ConclusionOur results show unequivocally that AMPK pathway is highly activated in papillary thyroid carcinomas; however, more studies are necessary to understand the pathophysiological significance of AMPK activation in thyroid carcinogenesis.

The incidence of differentiated thyroid cancer (DTC) is increasing worldwide, especially among small (≤2 cm) tumors. Overall, small DTC have an excellent prognosis and low mortality rate. Still, a proportion of these patients will experience recurrent/persistent disease. Careful risk stratification makes it possible to individualize treatment, avoiding unnecessary procedures and guarantees a good long-term prognosis with low recurrence risk. Recent studies evaluated the impact of the extent of surgery and radioiodine therapy, providing new evidence regarding treatment approach. Therefore, is time to reconsider clinical management and treatment of small DTC. Based on current data, in patients with small tumors and no additional risk factors, a conservative surgical approach without radioiodine therapy might be appropriated. More extensive surgery and radioiodine therapy could be proposed for small tumors exhibiting more aggressive features, such as lymph node metastasis, multifocality, vascular involvement, extra-thyroidal invasion or unfavorable molecular biology.