Diagnosis Of Differentiated Thyroid Carcinoma Research Articles

THU223 Molecular Makeup Of Differentiated Thyroid Carcinoma In A Free-standing Children’s Hospital With A Predominantly Hispanic Population

Abstract Disclosure: A. Martinez: None. D. Baboun: None. N. Solano: None. R. Restrepo: None. C. Brathwaite: None. F. Alkhoury: None. A. Carrillo-Iregui: None. Background: Molecular testing has been incorporated into the clinical management of thyroid nodules in adults. The prevalence of oncogenic mutations and the role of molecular testing in the evaluation of thyroid nodules in children and adolescents have yet to be established. Objective: The purpose of this study is to identify the molecular makeup of thyroid nodules in patients diagnosed with differentiated thyroid carcinoma (DTC) at a free-standing children’s hospital with a predominantly Hispanic population. Methods: Upon Institutional Review Board approval, we reviewed the charts of all patients with a final diagnosis of DTC between 2012 and 2022. We analyzed demographics, histopathological diagnoses, and molecular oncogenic markers of pathology specimens when available. Statistical analysis was performed using Welch’s t-test and Fisher’s exact test. Results: Fifty-five patients between 8-20 years of age were diagnosed with DTC. Forty-nine (89.1%) patients identified as Hispanic, and 41 (74.6%) were females. Fifty-two (94.5%) patients had papillary thyroid carcinoma, and 3 (5.5%) had follicular thyroid carcinoma. Molecular testing was performed on 33 patients, of which 30 were positive for mutations and 3 undetected. BRAF V600E (43.3%) and RET/PTC (23.3%) were the most prevalent mutations detected. The average ages of patients with BRAF V600E and RET/PTC were 15.5 and 13.3 years, respectively with no statistical significance (p=.22). The average tumor sizes of patients with BRAF V600E and RET/PTC were 1.82 ± 0.95 cm and 2.5 ± 1.21 cm, respectively with no statistical significance (p=.12). Of the patients with BRAF V600E, 53.9% had lymph node involvement and none had metastasis. Of the patients with RET/PTC, 42.9% had lymph node involvement and 14.3% had metastasis. When comparing BRAFV600E and RET/PTC, there was no statistical difference with respect to lymph node involvement or metastasis (p=1.0 and p=.35, respectively). Other mutations detected include PAX8-PPARg (10.0%), ALK fusion (6.7%), RAS (3.3%), PTEN (3.3%), compound KIT and TSHR (3.3%), TRIM27-RET (3.3%), and other (3.3%). Notably, one patient presented with TRIM27-RET, which was associated with total lobe involvement, lymph node involvement, and distal metastasis. Conclusions: BRAF V600E and RET/PTC were the most prevalent molecular markers correlated with DTC in our predominantly Hispanic cohort. In comparison to BRAF V600E, RET/PTC was more prevalent in younger patients and was associated with a greater tumor size. We did not find any statistically significant differences with respect to age, tumor size, lymph node involvement, or metastasis between the aforementioned molecular markers. Incorporating molecular testing to supplement malignancy evaluation may improve clinical and surgical management for pediatric patients with DTC. Presentation: Thursday, June 15, 2023

THU224 Is Chronic Lymphocytic Thyroiditis Associated With Aggressive Differentiated Thyroid Cancer In A Predominantly Hispanic Pediatric Population?

Abstract Disclosure: N. Solano: None. D. Baboun: None. A. Martinez-Sanchez: None. A. Diaz: None. A. Carrillo-Iregui: None. F. Alkhoury: None. Background: The risk of developing papillary thyroid carcinoma (PTC) appears to be increased among patients with chronic lymphocytic thyroiditis (CLT). Studies in adults have shown that the presence of CLT is associated with less aggressive PTC; however, this correlation is unclear in pediatric patients. Objective: The purpose of this study is to determine a possible correlation between CLT and markers of aggression severity using histopathological findings, tumor size, and lymph node involvement among patients with differentiated thyroid carcinoma (DTC) in a free-standing children’s hospital with a predominantly Hispanic population. Methods: Upon Institutional Review Board approval, we performed a retrospective chart review from 2012-2022 of 55 patients with a final diagnosis of DTC. We analyzed the correlation between CLT and histopathological findings. Statistical analysis was performed by using t-tests and chi-squared tests. Results: The patients reviewed were between 8-20 years of age. Forty-nine (89.1%) patients identified as Hispanic, and 41 (74.6%) were females. Twenty-five (45.5%) patients had a diagnosis of CLT; 19 (76.0%) of these patients had classic PTC, 3 (12.0%) had the follicular variant of PTC, and 3 (12.00%) had another variant of PTC. Of the 30 (54.5%) patients who did not have CLT, 13 (43.3%) had the classic variant of PTC, 10 (33.3%) had the follicular variant of PTC, and 7 (23.3%) had another variant of PTC. The distribution of the histopathological findings was significant (p=.048). Patients with CLT had significantly smaller tumor sizes (1.8 vs. 2.5 cm, respectively [p=.048]). Of the 36 patients with lymph node involvement, 20 (55.6%) had CLT. Of the 19 patients without lymph node involvement, 5 (26.3%) had CLT. The association between the presence of CLT and lymph node involvement was significant (p=.038). Conclusions: In our population, patients with CLT had a significantly higher presence of the classic variant of PTC. Studies in adults have shown a tendency of these lesions to have a higher risk of disease than those with the follicular variant. Patients with CLT had a smaller tumor size, likely as a result of earlier detection of thyroid nodules due to frequent clinical evaluations and thyroid ultrasounds. However, patients with CLT tended to have a higher frequency of lymph node involvement. More studies with pediatric populations are needed to clarify the possible association between CLT and DTC. Presentation: Thursday, June 15, 2023

B-366 Thyroglobulin Reflex to Manage Thyroglobulin Autoantibody Interference in an Academic Medical Center: A Comparison of Two Immunoassays and an LC-MS/MS Assay in the Presence of Thyroglobulin Autoantibodies

Abstract Background Thyroglobulin (Tg) measurement is clinically important during the management of patients with differentiated thyroid carcinoma (DTC). Enzyme immunoassays (EIA) offer an affordable and highly automated method for measuring Tg. However, in the presence of thyroglobulin autoantibodies (TgAb), Tg levels may be falsely low in EIA assays due to interference. Tg testing using liquid chromatography tandem mass spectrometry (LC-MS/MS) is recommended when TgAb are detected. We implemented a reflex test to Tg by LC-MS/MS when TgAb are present and may cause interference in EIA tests. Reflex cutoffs need to be refined to minimize interferences while preventing unnecessary reflex testing. Methods Our objective was to compare two Tg EIAs and an LC-MS/MS assay in the presence of TgAb, and the prevalence and clinical performance of two TgAb EIAs. TgAb was measured on the Abbott Architect and Beckman Coulter DxI assays in 602 samples from patients with DTC and other suspected thyroid conditions between 11/29/2022 and 2/1/2023. In all samples, Tg was measured by two EIAs, the Siemens Immulite and Beckman Coulter DxI. When TgAb by the Abbott assay was >14.4 IU/mL, Tg was tested by LC-MS/MS in a reference lab. Results Fifty-seven specimens reflexed to LC-MS/MS testing based on the cutoff >14.4 IU/mL for the Abbott assay. Of these 57 samples, 42 samples would have reflexed by the Abbott and Beckman Coulter assay (cutoff ≥ 4.0 IU/mL) and 15 would not have reflexed using the Beckman Coulter assay. Fifteen specimens would have reflexed to LC-MS/MS using the Beckman Coulter cutoff, but not according to the Abbott assay. The TgAb positivity rate was 9.5% for both assays, and the overall reflexing agreement was 95.0% in the entire cohort of 602 results. For the 15 specimens that the Beckman Coulter assay would not have reflexed, LC-MS/MS and the EIAs demonstrated clinically matching results in 13 specimens. Twenty-nine of 57 specimens had undetectable Tg levels (<0.5 ng/mL) by LC-MS/MS, also had Tg <0.5 ng/mL by the Beckman Coulter assay, while 27 measured at below the limit of quantitation (<0.9 ng/mL) for the Siemens Immulite assay. Five results were discrepant near detectable ranges (detectable by LC-MS/MS and falsely low by EIA), with one result more closely agreeing to the Siemens EIA (a patient with no DTC diagnosis) and the other four more closely agreeing to the Beckman Coulter EIA. Linear regression comparing the Siemens Immulite (LC-MS/MS = 0.7 * Immulite + 8.7, r = 0.99) and Beckman Coulter DxI (LC-MS/MS = 1.2 * DXI – 0.6, r = 1.00) to the LC-MS/MS assay, demonstrated biased results but strong correlations. Conclusion The Beckman Coulter EIA demonstrated better agreement with LC-MS/MS results at or near lower limits of quantitation in patients with TgAb. While linear regression demonstrated strong correlation between assays, the five discrepant results indicate that TgAb interference impacts Tg results by EIA. The TgAb threshold for reflex testing should continue to be investigated.

Application of thyroglobulin and anti-thyroglobulin antibody combined with emission computed tomography in the adjuvant diagnosis of differentiated thyroid carcinoma

Purpose Thyroid nodules are a kind of common endocrine system disease, with approximately 5% of them developing into malignant lesions, the most common of which belong to differentiated thyroid carcinoma (DTC). Accurate differential diagnosis using reliable methods and targeted treatment of benign and malignant thyroid nodules are of great significance to improve patient outcomes. This study mainly investigates the diagnostic value of thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-TgAb) combined with emission computed tomography (ECT) in the adjuvant diagnosis DTC. Methods All the data of 387 histopathologically diagnosed DTC patients (observation group) and 151 patients with nodular goiter (control group) admitted between June 2019 and June 2021 were collected and retrospectively analyzed. Serum Tg and anti-TgAb levels were detected in all subjects. In addition, all patients in the observation group underwent thyroid ECT, and the results were compared with the pathological findings. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic performance of Tg, TgAb and thyroid ECT, either alone or in combination, in patients with thyroid cancer (TC). Results The consistency test showed that Tg (Kappa-value = 0.370) and anti-TgAb (Kappa-value = 0.393) had generally consistent efficiency with pathological findings in the diagnosis of DTC; ECT (Kappa-value = 0.625) and the combined diagnosis of the three (Kappa-value = 0.757) showed higher consistency than the pathological diagnosis, of which the combined diagnosis contributed to an even higher consistency. The combined diagnosis of Tg, anti-TgAb, and thyroid ECT outperformed either of these alone in DTC diagnosis, with a sensitivity of 91.5%, a specificity of 86.1%, and an accuracy of 90%. Conclusions The combination of Tg. anti-TgAb, and RNI can effectively improve the diagnostic accuracy of DTC and reduce the missed diagnosis rate, which has important reference significance for clinical diagnosis and treatment of TC.

Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol

Background Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.

Comparison of endoscopic thyroidectomy by complete areola approach and conventional open surgery in the treatment of differentiated thyroid carcinoma: Aretrospective study and meta-analysis.

The feasibility of endoscopic thyroidectomy by complete areola approach (ETCA) remains controversial. This study was conducted by combining our clinical data with the data obtained from a systematic review literature search to examine the effectiveness and safety of ETCA compared with conventional open thyroidectomy (COT) in differentiated thyroid carcinoma (DTC). A total of 136 patients with a diagnosis of DTC who underwent unilateral thyroidectomy with central neck dissection from August 2020 to June 2021 were enrolled. The enrolled patients were divided into the ETCA group (n = 73) and the COT group (n = 63). The operative time, intraoperative bleeding volume, number of removed lymph nodes, number of metastatic lymph nodes, postoperative drainage volume, length of postoperative hospital stay, postoperative parathyroid hormone (PTH) levels, and complications were analyzed. Then, a systemic review and comprehensive literature search were conducted by using PubMed, Google Scholar, Embase, Web of Science, CNKI, Wanfang, and VIP database up to June 2022. Review Manager software version 5.3 was used for the meta-analysis. The results of clinical data showed that there were significant differences between the two groups in the operative time, intraoperative bleeding volume, removed lymph nodes, and postoperative drainage volume. There were no statistical differences in the length of postoperative hospital stay, number of metastatic lymph nodes, postoperative PTH level, and complications. In the systematic review and meta-analysis, 2,153 patients from fourteen studies (including our data) were ultimately included. The results of the meta-analysis found that ETCA had a longer operative time, larger postoperative drainage volume, and lower intraoperative bleeding volume. In terms of the length of postoperative hospital stay, the number of removed lymph nodes, and surgical complications, there was no significant difference between the two groups. ETCA poses lower surgical bleeding and better cosmetic appearance compared with COT, while the length of operation and postoperative drainage in ETCA is less favorable compared with COT. In addition, ETCA is not inferior to COT in terms of the postoperative hospitalization stay, the number of removed lymph nodes, and surgical complications. Given its overall advantages and risks, ETCA is an effective and safe alternative for patients with cosmetic concerns.

Identification and Validation of a Prognostic Signature Based on Methylation Profiles and Methylation-Driven Gene DAB2 as a Prognostic Biomarker in Differentiated Thyroid Carcinoma.

Recurrence is the major death cause of differentiated thyroid carcinoma (DTC), and a better understanding of recurrence risk at early stage may lead to make the optimal medical decision to improve patients' prognosis. The 2015 American Thyroid Association (ATA) risk stratification system primary based on clinic-pathologic features is the most commonly used to describe the initial risk of persistent/recurrent disease. Besides, multiple prognostics models based on multigenes expression profiles have been developed to predict the recurrence risk of DTC patients. Recent evidences indicated that aberrant DNA methylation is involved in the initiation and progression of DTC and can be useful biomarkers for clinical diagnosis and prognosis prediction of DTC. Therefore, there is a need for integrating gene methylation feature to assess the recurrence risk of DTC. Gene methylation profile from The Cancer Genome Atlas (TCGA) was used to construct a recurrence risk model of DTC by successively performed univariate Cox regression, LASSO regression, and multivariate Cox regression. Two Gene Expression Omnibus (GEO) methylation cohorts of DTC were utilized to validate the predictive value of the methylation profiles model as external cohort by receiver operating characteristic (ROC) curve and survival analysis. Besides, CCK-8, colony-formation assay, transwell, and scratch-wound assay were used to investigate the biological significance of critical gene in the model. In our study, we constructed and validated a prognostic signature based on methylation profiles of SPTA1, APCS, and DAB2 and constructed a nomogram based on the methylation-related model, age, and AJCC_T stage that could provide evidence for the long-term treatment and management of DTC patients. Besides, in vitro experiments showed that DAB2 inhibited proliferation, colony-formation, and migration of BCPAP cells and the gene set enrichment analysis and immune infiltration analysis showed that DAB2 may promote antitumor immunity in DTC. In conclusion, promoter hypermethylation and loss expression of DAB2 in DTC may be a biomarker of unfavorable prognosis and poor response to immune therapy.

Tumor size is an independent negative prognostic factor for event free survival in children with differentiated thyroid cancer.

BackgroundThe incidence of pediatric differentiated thyroid carcinoma (DTC) is increasing. Despite the advanced disease at presentation, the overall prognosis of DTC in children is excellent. The aim of this study is to investigate the risk stratifying factors for event free survival (EFS) of pediatric DTC from Middle Eastern ethnicity.MethodsEighty-eight patients aged ≤18 years with diagnosis of primary DTC were retrospectively analyzed. Cox proportional hazards model were used to calculate Hazard Ratios (HR) and Kaplan–Meier analysis were conducted to investigate EFS.ResultsEighty-eight (23 males and 65 females) pediatric DTCs who underwent surgery and radioactive iodine therapy had been reported (median age at diagnosis 15 years; range 5.9-17.9), with lymph node metastasis (LNM) noted in 70.5% and distant metastasis in 13.6%. Mean follow-up was 8.4 years. Ten-year overall survival rate was 98.4% while 10-year EFS was 79.2%. EFS was negatively impacted by the presence of LNM, distant metastasis and tumor size >4cm. American Thyroid Association risk stratification did not impact EFS in our cohort. Multivariate analysis revealed tumor size >4cm (HR = 5.34; 95% confidence interval (CI) = 1.36 – 20.22; p = 0.0177) and distant metastasis (HR = 8.73; 95% CI = 1.48 – 60.05; p = 0.0154) as independent negative prognostic factors for EFS.ConclusionsPrimary tumor size and the presence of distant metastasis at diagnosis are the only independent prognostic risk factors for EFS in pediatric DTC in Middle Eastern ethnicity. Children with tumor size over 4cm had poor EFS, which may justify the need of more aggressive treatment and frequent follow-up.

Age, American Thyroid Association Risk Group, and Response to Therapy Are Prognostic Factors in Children With Differentiated Thyroid Cancer.

Against the background of increasing incidence, pediatric differentiated thyroid carcinoma (DTC) frequently presents with advanced disease and high recurrence rates while prognosis remains excellent. We investigated the use of a pediatric classification and an adult response to therapy risk stratification for pediatric DTC patients and their implications for adaptation of treatment and follow-up. Data from patients aged <18 years with a diagnosis of primary DTC, registered with the German Pediatric Oncology Hematology-Malignant Endocrine Tumor registry since 1995, were analyzed. For risk prediction, patients were retrospectively assigned to the American Thyroid Association (ATA) risk groups and evaluated for response to therapy. By October 2019, 354 patients with DTC had been reported (median age at diagnosis 13.7 years, range 3.6-17.9) with lymph node and distant metastases in 74.3% and 24.5%. Mean follow-up was 4.1 years (range 0-20.6). Ten-year overall and event-free survival (EFS) rates were 98.9% and 78.1%. EFS was impaired for patients with lymph node and distant metastases (P < .001), positive postoperative thyroglobulin (P = .006), incomplete resection (P = .002), sequential surgeries to achieve total thyroidectomy (P = .042), invasion of capsule (P < .001) and lymph vessels (P = .005), infiltration of surrounding soft tissues (P < .001), tumor multifocality (P < .001), ATA intermediate- and high-risk group (P < .001), and age <10 years (P < .001). Multivariate analysis revealed age <10 years at diagnosis, ATA high-risk level, and poor response to therapy as significant negative prognostic factors for EFS. Age, ATA risk group, and response to therapy emerged as significant prognostic factors for EFS in pediatric patients with DTC, requiring risk-adapted individualized therapy and follow-up.

Imaging Algorithm-Based Real-Time Shear Wave Elastography Combined with Thyroglobulin Antibodies in Diagnosis of Thyroid Cancer

To analyze the effect of real-time shear wave elastography (SWE) optimized by mathematical algorithms combined with thyroglobulin antibodies (TGAb) on the clinical diagnosis of differentiated thyroid carcinoma (DTC), a hybrid displacement estimation algorithm based on weighted phase separation and two-dimensional cross correlation was proposed. 102 patients with DTC were divided into a test group (TGAb-positive) and a control group (TGAb-negative). Real-time SWE based on hybrid displacement estimation algorithm was performed. Receiver operating characteristic (ROC) curve was adopted to analyze the characteristics of real-time SWE and its combination with TGAb to detect the sensitivity, specificity, and area under the curve (AUC) of the malignant degree of thyroid cancer. The results showed that the preoperative thyroid-stimulating hormone (TSH), thyroglobulin autoantibodies (TGAb), and thyroid peroxidase antibody (TPOAb) of TGAb-positive patients were higher than those of the TGAb-negative group ( P &lt; 0.05 ). The preoperative tumors of TGAb-positive patients were multifocal, and the tumor size was larger than that of the TGAb-negative patients ( P &lt; 0.05 ). The maximum Young’s modulus Emax of TGAb-positive patients was greater than that of TGAb-negative group ( P &lt; 0.05 ). In addition, there was a very significant positive correlation between the patient’s TGAb level and Emax of Young’s modulus ( P &lt; 0.001 ). The sensitivity, specificity, and AUC of the joint detection of real-time SWE Emax and TGAb for the malignant degree of thyroid cancer were significantly greater than those of the single real-time SWE and TGAb, and the difference was substantial ( P &lt; 0.05 ). In short, joint detection of real-time SWE based on hybrid displacement estimation algorithm combined with TGAb had high sensitivity, specificity, and AUC for the diagnosis of DTC, which was suitable for clinical application.

Overexpression of centromere protein K (CENPK) gene in Differentiated Thyroid Carcinoma promote cell Proliferation and Migration

ABSTRACT Differentiated thyroid carcinoma (DTC) is one of the most common malignant tumors. Increasing evidence indicates that centromere protein K(CENPK) may play a key role in promoting carcinogenesis. The expression, biological functions, and clinical significance of CENPK in DTC are still unclear. The CENPK expression in the DTC specimen was confirmed using quantitative real-time PCR and Western blot. The expression of CENPK was silenced and promoted by lentivirus-mediated transfection with shRNA sequences or CENPK plasmid targeting CENPK in TPC1 and FTC-133 cells, respectively. Colony formation, Cell Counting Kit-8 (CCK-8), Transwell invasion, and scratch assays were performed to assess the malignant biological properties of FTC-133 and TPC1 cells. Tumorigenicity assay was performed using C57BL/6 mice to explore the influence of CENPK on the growth of TPC1. The present work suggested that the expression of CENPK remarkably increased in follicular thyroid cancer and papillary thyroid cancer tissue samples at the mRNA level. Immunohistochemical staining also showed consistent results at the protein level. In addition, CENPK mRNA expression level showed great value in diagnosis of DTC. Knockdown of CENPK significantly inhibited the invasion and migration of TPC1 and FTC-133 cells. In contrast, CENPK overexpression promoted invasion and migration of TPC1 and FTC-133 cells. Knockdown and overexpression of CENPK showed consistent effect on DTC tumor growth and expression of Ki-67 invivo. Our results indicated that CENPK was evidently upregulated in DTC. Knocking down CENPK suppressed TPC1 cell proliferation, invasion and migration. Targeting the CENPK may be anovel therapeutic method for DTC.

Distant Metastases From Childhood Differentiated Thyroid Carcinoma: Clinical Course and Mutational Landscape.

Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

Acromegaly and thyroid cancer: analysis of evolution in a series of patients

BackgroundAcromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution.MethodsThis is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0.ResultsMedian age of patients at diagnosis of acromegaly was 49.5 years (range 12–69). The median delay in diagnosis of acromegaly was 3 years (range 0.5–23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18–69).At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5–7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb.Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months.When comparing RFU between acromegalics and controls no statistically significant differences were found.ConclusionsPatients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

Clinical considerations for the treatment of secondary differentiated thyroid carcinoma in childhood cancer survivors.

The incidence of differentiated thyroid carcinoma (DTC) has increased rapidly over the past several years. Thus far, the only conclusively established risk factor for developing DTC is exposure to ionizing radiation, especially when the exposure occurs in childhood. Since the number of childhood cancer survivors (CCS) is increasing due to improvements in treatment and supportive care, the number of patients who will develop DTC after surviving childhood cancer (secondary thyroid cancer) is also expected to rise. Currently, there are no recommendations for management of thyroid cancer specifically for patients who develop DTC as a consequence of cancer therapy during childhood. Since complications or late effects from prior cancer treatment may elevate the risk of toxicity from DTC therapy, the medical history of CCS should be considered carefully in choosing DTC treatment. In this paper, we emphasize how the occurrence and treatment of the initial childhood malignancy affects the medical and psychosocial factors that will play a role in the diagnosis and treatment of a secondary DTC. We present considerations for clinicians to use in the management of patients with secondary DTC, based on the available evidence combined with experience-based opinions of the authors.

Personalized management of differentiated thyroid cancer in real life \u2013 practical guidance from a multidisciplinary panel of experts

PurposeThe standard of care for differentiated thyroid carcinoma (DTC) includes surgery, risk-adapted postoperative radioiodine therapy (RaIT), individualized thyroid hormone therapy, and follow-up for detection of patients with persistent or recurrent disease. In 2019, the nine Martinique Principles for managing thyroid cancer were developed by the American Thyroid Association, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and European Thyroid Association. In this review, we present our clinical practice recommendations with regard to implementing these principles in the diagnosis, treatment, and long-term follow-up of patients with DTC.MethodsA multidisciplinary panel of five thyroid cancer experts addressed the implementation of the Martinique Principles in routine clinical practice based on clinical experience and evidence from the literature.ResultsWe provide a suggested approach for the assessment and diagnosis of DTC in routine clinical practice, including the use of neck ultrasound, measurement of serum thyroid-stimulating hormone and calcitonin, fine-needle aspiration, cytology, and molecular imaging. Recommendations for the use of surgery (lobectomy vs. total thyroidectomy) and postoperative RaIT are also provided. Long-term follow-up with neck ultrasound and measurement of serum anti-thyroglobulin antibody and basal/stimulated thyroglobulin is standard, with 123/131I radioiodine diagnostic whole-body scans and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography suggested in selected patients. Management of metastatic DTC should involve a multidisciplinary team.ConclusionsIn routine clinical practice, the Martinique Principles should be implemented in order to optimize clinical management/outcomes of patients with DTC.

Pulmonary and overall healthcare utilization after childhood and young adult thyroid cancer.

Differentiated thyroid carcinoma (DTC) in children, adolescents, and young adults is associated with excellent prognosis. However, little is known about the long-term utilization of healthcare resources among survivors. The objective of this study was to compare the utilization of healthcare resources among DTC survivors to the general population, with a focus on pulmonary-related resource utilization. Population-based linked data were used to retrospectively ascertain DTC patients from the Ontario Cancer Registry, age <30 years at diagnosis between 1992 and 2011. DTC cases were individually matched 1:10 to the general population on age, sex, diagnosis year, and rural status. Billing records for all-cause hospitalizations, emergency department visits, pulmonary subspecialist visits, and chest imaging were compared using incidence rate ratios (IRR). A total of 2456 individuals with DTC were identified, with women representing the majority (82.8%) of cases. Compared to controls, hospitalization and emergency department visit IRRs were 2.56 (95% CI, 2.49-2.63) and 2.22 (95% CI, 2.18-2.26), respectively. An excess of pulmonary diagnostic imaging was observed for chest radiography (IRR, 2.7; 95% CI, 2.6-2.8) and pulmonary CT's (IRR, 17.5; 95% CI, 15.8-19.3). Patients who underwent radioactive iodine therapy had a higher incidence of pulmonary-related healthcare utilization than those who did not. The highest healthcare utilization for all modalities was observed in the 30 to 90 days after DTC diagnosis with a steady decline further from diagnosis; however, elevated utilization was observed throughout the observation period. Health services utilization is high for primary DTC survivors, irrespective of the time since diagnosis. Radioactive iodine therapy is associated with higher rates of utilization. These findings have ramifications for treatment, surveillance and for policy formulation.

Long-Term Effects of Radioiodine Treatment on Female Fertility in Survivors of Childhood Differentiated Thyroid Carcinoma

Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1-39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3-24.7) years. The median cumulative dose of 131I administered was 7.4 (IQR 3.7-13.0) GBq/200.0 (IQR 100.0-350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0-3.7) μg/L vs. 1.6 (IQR 0.6-3.1) μg/L, respectively, p = 0.244]. The cumulative dose of 131I was not associated with AMH levels in DTC survivors (rs = 0.210, p = 0.130). Conclusions: Female survivors of DTC who received 131I treatment during childhood do not appear to have major abnormalities in reproductive characteristics nor in predictors of ovarian failure.

Correlation studies of ultrasonic morphological types and the biological variation in calcification of the differentiated thyroid cancer

Objective To explore the correlation between ultrasound features and tumor biological variation with calcification morphological types in differentiated thyroid carcinoma (DTC). Methods The clinical data of 598 patients with DTC calcification diagnosed by ultrasound, surgery and clinicopathology were retrospectively analyzed. According to the 2017 edition of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) classification system standard, DTC ultrasonic calcification morphological characteristics were divided into 5 types, and the correlation between DTC ultrasonic calcification morphological types and tumor biological characteristics and their variations were analyzed by Spearman correlation analysis. Results Of the 598 patients, 527 cases (88.13%) were typical papillary thyroid cancer(PTC), 27 cases (4.52%) were typical follicular thyroid cancer(FTC), and 44 cases (7.36%) were variant subtype (including 25 cases of follicular type, 9 cases of high cell type, 6 cases of clear cell type and 4 cases of eosinophilic type). TI-RADS diagnosis: 44 cases (7.36%) were Ⅰ~Ⅲ class, 179 cases (29.93%) were Ⅳ class performing fine needle aspiration cytology(FNAC), 375 cases (62.71%) were Ⅴ class. The coincidence rate between ultrasound and clinicopathological diagnosis was 92.64% (554/598). Morphological types of ultrasonic calcification in 554 cases of DTC: type Ⅰ microcalcification in 416 cases (75.09%); type Ⅱ calcification in 71 cases (12.82%); type Ⅲ calcification in 41 cases (7.40%); type Ⅳ calcification in 20 cases (3.61%); type Ⅴ calcification in 6 cases (1.08%). There were correlations between type Ⅰ, Ⅱ, Ⅲ ultrasonic calcification morphological types and the tumor biological characteristics and its variant subtypes of DTC(r=0.634, 0.592, 0.479; all P=0.01). Conclusions TI-RADS Ⅳ-Ⅴ class level+ Adler Ⅱ-Ⅲ blood flow has a high practical value for the ultrasonic diagnosis of DTC, and FNAC can be performed in suspicious type Ⅳ DTC. Type Ⅰ-Ⅲ ultrasonic calcification morphological types and the main types of tumor biological characteristics and its variant of DTC, and has an important clinical value for the diagnosis of DTC by ultrasound, which provides an important reference basis for guiding FNAC, selecting surgical procedure, postoperative follow-up and prognosis judgment. Key words: Ultrasonography; Thyroid cancer, differentiated; Calcification type; Tumor biology

Postoperative Radioiodine Treatment within 9\xa0Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma

PurposeAlthough postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC.MaterialThe analyzed group involved 701 DTC patients staged pT1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5–15.2).ResultsBased on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant.ConclusionIf postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.

Body Composition, Resting Energy Expenditure, and Metabolic Changes in Women Diagnosed with Differentiated Thyroid Carcinoma.

Background: Thyroid hormones heavily impact energy expenditure, body mass, and body composition. Their role in the state of exogenous subclinical hyperthyroidism in differentiated thyroid carcinoma (DTC) patients, however, is less well defined. The first aim of this study was to assess changes in body weight, body composition, resting energy expenditure (REE), respiratory quotient (RQ), and metabolic parameters in female DTC patients, starting from the phase of a euthyroid state before total thyroidectomy through the subsequent year after thyrotropin (TSH) suppression. The second aim was to assess the relationship between these variables and thyroid function parameters. Methods: This observational case series analyzed changes in body composition, calorimetric, and metabolic parameters of 15 DTC female patients at 5 time points: (1) at initial DTC diagnosis (euthyroid state), (2) at 2-3 weeks after thyroidectomy (hypothyroid state), (3) at 2-3 months of levothyroxine (LT4) treatment (exogenous euthyroid state), (4) after 6-9 months, and (5) after 1 year of TSH suppressive LT4 therapy (exogenous subclinical hyperthyroid state). A generalized estimating equation (GEE) analysis was performed to estimate the longitudinal correlations of the total triiodothyronine (TT3)/free thyroxine (fT4) ratio (as an independent variable) with body composition, metabolic, and calorimetric parameter changes (as dependent variables). Results: REE, REE per kilogram of lean body mass (REE/LBM), pulse, and systolic and diastolic blood pressure were significantly higher after TSH suppressive LT4 therapy. The GEE analysis revealed longitudinal negative correlations between the TT3/fT4 ratio and systolic blood pressure, fasting blood glucose, body mass index, android (abdominal wall and visceral mesentery) fat distribution, trunk, and arm fat distribution, REE, and REE/LBM. There was a positive correlation with RQ. Conclusions: REE, REE/LBM, pulse, and systolic and diastolic blood pressure were significantly higher after thyroidectomy, radioiodine and TSH suppressive therapy in female DTC patients, while no changes were observed in body weight or body composition. A lower TT3/fT4 ratio longitudinally correlated with increases in REE, REE/LBM, abdominal fat distribution, systolic blood pressure, and fasting blood glucose, as well as with decreased RQ. These findings highlight the importance of judicial balancing of the benefits and detriments of TSH suppression with subsequent decreased TT3/fT4 ratios for female DTC patients.