Lymphocytic Thyroiditis is Associated with Increased Number of Benign Cervical Nodes and Fewer Central Neck Compartment Metastatic Lymph Nodes in Patients with Differentiated Thyroid Cancer

Objective: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection.Methods: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013.Results: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT.Conclusion: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear.Abbreviations:CCND = central compartment node dissectionDTC = differentiated thyroid cancerHT = Hashimoto thyroiditisLT = lymphocytic thyroiditisTgAb = thyroglobulin antibodyTPO = thyroid peroxidase     

Pre-Ablation Thyroglobulin and Thyroglobulin to Thyroid-Stimulating Hormone Ratio may be Associated with Pulmonary Metastases in Children with Differentiated Thyroid Cancer

Objective: Pediatric differentiated thyroid cancer (DTC) frequently presents with extensive disease. We studied the value of pre-ablation thyroglobulin (Tg) and Tg normalized to thyroid-stimulating hormone (TSH) levels in predicting distant metastases in pediatric patients with DTC.Methods: This is a retrospective cohort study of patients <21 years old who underwent thyroidectomy followed by ¹³¹I ablation for DTC at 3 university hospitals over 20 years. Tg levels and the Tg/TSH ratio following surgery but prior to ¹³¹I ablation were assessed. The presence of distant metastatic disease was determined from the postablation whole-body scan.Results: We studied 44 patients with a mean age of 15.2 years (range 7 to 21 years) and mean tumor size of 2.8 cm. Eight patients had distant metastases and had a higher mean pre-ablation Tg value compared to patients without distant metastases (1,037 μg/L versus 93.5 μg/L, P<.01). The pre-ablation Tg/TSH ratio was also associated with the presence of distant metastases: 12.5 ± 18.8 μg/mU in patients with distant metastases versus 0.7 ± 1.8 μg/mU in patients without (P<.01). A nomogram to predict distant metastases yielded areas under the receiver operating characteristic curve of 0.85 for Tg and 0.83 for Tg/TSH ratio.Conclusion: After initial thyroidectomy, elevated preablation Tg and Tg/TSH ratio are associated with distant metastatic disease in pediatric DTC. This may inform the decision to ablate with ¹³¹I, as well as the dosage.Abbreviations:ATA = American Thyroid AssociationCI = confidence intervalDTC = differentiated thyroid cancerOR = odds ratioROC = receiver operating characteristicTg = thyroglobulin     

Unfavorable Responses to Radioiodine Therapy in N1b Papillary Thyroid Cancer: A Propensity Score Matching Study

Objective: Regional nodal metastases carry prognostic significance in papillary thyroid cancer (PTC). However, whether different locational nodal metastases correlate with different therapeutic responses remains controversial. We innovatively applied the response to therapy restratification system to evaluate the dynamic disease status after surgery and radioactive iodine (RAI) therapy in PTC patients with different locational nodal metastases.Methods: A total of 585 nondistant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled. Patients with nodal metastases were categorized into N1a and N1b groups. Propensity score matching was used to balance the bias between the 2 groups. Therapeutic responses were dynamically evaluated, and responses to RAI therapy were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR).Results: N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin (Ps-Tg) level than N1a group patients (7.4 ng/mL versus 3.2ng/mL, P<.001). After RAI therapy, N1b group patients took a longer time to achieve ER (9.86 months versus 3.29 months, P<.001) and exhibited a higher proportion of non-ER (IDR, BIR, and SIR) (39.15% versus 17.46%, P<.001) compared to N1a group patients. In logistic regression, N1b and Ps-Tg ≥10 ng/mL were confirmed to be independent factors predicting non-ER (odds ratio: 2.591, and 9.196, respectively). In Cox regression, patients with N1b disease and Ps-Tg ≥10 ng/mL showed significantly lower hazards for achieving ER (hazard ratio: 0.564, and 0.223, respectively).Conclusion: N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients. N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy.Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; BRAF^V600E = proto-oncogene B-Raf V600E mutation; CI = confidence interval; CT = computed tomography; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; ER = excellent response; ETE = extrathyroidal extension; HR = hazard ratio; IDR = indeterminate response; LNM = lymph node metastasis; N1a = central cervical LNM; N1b = lateral cervical LNM; OR = odds ratio; PSM = propensity score matching; Ps-Tg = pre-ablation stimulated thyroglobulin; PTC = papillary thyroid cancer; RAI = radioactive iodine; SIR = structural incomplete response; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone     

Effect of Post-Surgical Rai Therapy on Parathyroid Function in Patients with Differentiated Thyroid Cancer

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients.Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (^99mTc)-pertechnetate thyroid scan (^99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (¹³¹I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) ¹³¹I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment.Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of ^99mTc thyroid scan, scores of ¹³¹I WBS, Tumor (T) stage, and Node (N) stage.Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan     

Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level

Objective: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes.Methods: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated.Results: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC.Conclusion: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels.Abbreviations: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma     

Prognosis of Differentiated Thyroid Carcinoma in Patients with Graves Disease: A Systematic Review and Meta-Analysis

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC.Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model.Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I², 6.5%; P =.381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I², 0.0%; P =.497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up.Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD.Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone     

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

ObjectiveIn order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC.MethodsWe have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines.ResultsExogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW.ConclusionThe rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC. (Endocr Pract. 2013;19:139-148)     

Comparison of Radioiodine Utilization in Adolescent and Young Adult and Older Thyroid Cancer Patients

ObjectiveDifferentiated thyroid cancer (DTC) is 1 of the most common cancers in adolescents and young adults (AYA, ages 15-39). Although most AYAs with DTC are considered low risk compared to older patients, there are no specific postoperative radioiodine (RAI) treatment recommendations despite the potential adverse effects specific to this age group, namely secondary malignancies and fertility difficulties. This study compares factors influencing RAI utilization in AYA and older patients.MethodsA total of 5,687 primary DTC patients were identified from the SEER (Surveillance, Epidemiology, and End Results) database between January 1, 2004 and January 31, 2009. The 2009 American Thyroid Association (ATA) guidelines were used to classify patients as low (LR) or intermediate/high risk (IHR) based on tumor characteristics. Multivariate logistic regression analysis was performed.ResultsOverall, 56.9% of AYA (n = 1,963) patients received postoperative RAI compared to 52.2% of older (n = 3,724) patients (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.09-1.35, P = .001). For AYA patients, having a total thyroidectomy (TTx) (OR: 3.53, 95% CI: 2.7-4.61, P < .001) predicted RAI in a multivariate model whereas LR status (OR: 0.52, 95% CI: 0.43-0.63, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.29-0.52, P < .001) decreased the probability. All 3 factors similarly affected older patients in addition to an increased likelihood after lymph node (LN) dissection. Additionally, after selecting for TTx (n = 1,077), no factor influenced the use of RAI for AYA patients, whereas LR (OR: 0.30, 95% CI: 0.21-0.43, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.19-0.79, P = .008) were associated with decreased RAI use in older patients.ConclusionDespite their excellent prognosis, AYA thyroid cancer patients are more likely to receive postoperative RAI compared to older patients. Increased awareness of the unique survivorship implications for AYA patients will be an important aspect to address going forward. (Endocr Pract. 2014;20:405-411)     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Lateral Neck Dissection for Aggressive Variants of Well-Differentiated Thyroid Cancer

Objective: Well-differentiated thyroid cancer (WDTC) is characterized by favorable disease course and excellent survival. However, some histologic subtypes, known as aggressive histologic variants (AHVs), present a more aggressive behavior than conventional WDTC. The aim of this study was to evaluate the pattern of nodal involvement and factors influencing prognosis in N1b patients with AHVs.Methods: A multicentric retrospective analysis of patients who underwent therapeutic lateral neck dissection (ND) for WDTC between 1994 and 2015 was accomplished. AHVs included the following subtypes: tall cell, Hürtle cell, diffuse sclerosing, and poorly differentiated papillary thyroid cancer.Results: The study included a total of 352 N1b patients, 40 (11.4%) of whom had AHVs. AHVs present a similar distribution of positive nodes if compared with conventional WDTC. In AHV patients, 5-year overall survival (OS), disease-specific survival (DSS), locoregional control, and metastasis-free survival were 82.2%, 93.6%, 80.3%, and 87.3%, respectively. Advanced age (>55 years) was the only significant factor affecting survival (OS, P<.001; DSS, P = .011) in this group. In the AHV group, there were 9 (22.5%) recurrences; patients with regional recurrence and without distant metastases were effectively treated by surgery.Conclusion: The distribution of positive lymph nodes in case of AHVs is similar to that of conventional WDTC, with only level V at a relatively greater risk of harboring metastases in the former group. Survival outcomes in N1b patients with AHVs remain optimal. Total thyroidectomy, ND, and adjuvant radioiodine administration have been demonstrated to be effective treatments in the setting of AHVs.Abbreviations: AHV = aggressive histologic variant; DOD = died of disease; DSS = disease-specific survival; DSV = diffuse sclerosing variant; ETE = extrathyroidal extension; HCC = Hürthle cell carcinoma; LRC = locoregional control; LVI = lymphovascular invasion; MFS = metastasis-free survival; ND = neck dissection; NED = no evidence of disease; OS = overall survival; PDA = poorly differentiated areas; PTC = papillary thyroid carcinoma; RAI = radioiodine therapy; TCV = tall cell variant; WDTC = well-differentiated thyroid cancer     

Tumor Size is an Independent Predictor of Mortality Risk in Differentiated Thyroid Cancer Patients with T4 Disease

Objective: The eighth edition of the American Joint Committee on Cancer (AJCC) guideline on the tumor-node-metastasis staging system has been applied in clinical practice for thyroid cancer since 2018. However, using these criteria, a few studies have shown no significant difference between stage III and IV diseases amongst the differentiated thyroid cancer (DTC) patients. Thus, we aimed to study the underlying reason behind this observation.Methods: Patients were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The Cox proportional hazards regression model was used for the univariate and multivariate analyses to plot the Kaplan-Meier survival curves for overall survival (OS) and disease-specific survival (DSS).Results: A total of 1,431 patients had a median tumor size of 3.0 cm (range: 0.1 to 50 cm). When stratified by tumor size (≤2 cm, 2 to 4 cm, and >4 cm), lower survival rates were observed in patients with stage III (T4a) cancer and large tumor size than in those with stage IVA (T4b) cancer and small tumor size. Univariate and multivariate analyses showed that tumor size (≤4 cm versus >4 cm) is an independent prognostic factor for OS (P<.001) and DSS (P<.001) in DTC patients with T4a and T4b diseases.Conclusion: Tumor size is an independent prognostic factor for OS and DSS in DTC patients with T4 disease; tumor size-related modification of the T4 category can improve the AJCC staging system for DTC patient with stage III–IV diseases.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; DSS = disease-specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = Surveillance, Epidemiology, and End Results; TNM = tumor-node-metastasis     

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.Methods: Thyroid surgery cases at a single institution from 2005–2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound     

Clinical Features in Differentiated Thyroid Carcinoma Stratified By Lymph Node Status

Objective: Cervical lymph node (CLN) metastases (mets) often occur in differentiated thyroid cancer (DTC), especially in the central compartment, and are a major predictor of local recurrence. We examined clinical endpoints in three groups of patients based on status of lymph node involvement: those with definite lymph node involvement (N1), negative lymph nodes (N0), and no lymph nodes resected (Nx). We correlated these endpoints with clinical and pathologic features of these patients.Methods: Medical records of 261 patients with DTC who underwent thyroidectomy between 2006 and 2018 at our center were reviewed. Lymph node status of patients was categorized based on American Joint Committee on Cancer (AJCC) 8th edition criteria as N1, N0, and Nx. We performed statistical analysis to assess the differences among these groups, using one-way analysis of variance. When significant differences were found, pairwise comparisons were conducted among the three groups. Statistical significance was defined as 2-tailed P<.05 for all tests.Results: There were significant differences among the groups in tumor multicentricity, tumor category/size, AJCC stage, and the presence of thyroglobulin auto-antibodies (TgAbs). There were no difference in age, gender, or histopathology. N1 patients had a higher incidence of multicentricity, larger tumor sizes, and were more likely to have elevated TgAbs. There were no significant differences between the N0 and Nx groups.Conclusion: This study shows that larger and multi-centric tumors are associated with increased likelihood of CLN mets in DTC. We suggest increased vigilance for CLN mets in tumors >2 cm, multicentric tumors, and patients with elevated TgAbs.Abbreviations: AJCC = American Joint Committee on Cancer; CLN = cervical lymph node; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; mets = metastases; N0 = no cancer in any lymph nodes; N1 = cancer in a lymph node; N1a = cancer in a central compartment lymph node; N1b = cancer in a lateral neck lymph node; Nx = lymph nodes not resected or examined; PTC = papillary thyroid cancer; TgAb = thyroglobulin auto-antibody     

Does T Stage Affect Prognosis in Patients With Stage Iv B Differentiated Thyroid Cancer

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8^th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T &lsqb;primary tumor size], N &lsqb;regional lymph nodes], M &lsqb;distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival.Methods: DTC cases that were considered stage IV B in the AJCC 8^th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6^th standard) was categorized into T0–2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis.Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS.Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 &lsqb;SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 &lsqb;SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

Risk Factors for Nonremission and Progression-Free Survival after I-131 Therapy in Patients with Lung Metastasis from Differentiated Thyroid Cancer: A Single-Institute,Retrospective Analysis in Southern China

Objective: Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 (¹³¹I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of ¹³¹I therapy on pulmonary function and peripheral blood counts in the same cohort of patients.Methods: The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria.Results: Multivariate Cox regression analysis indicated that age ≥45 years and ¹³¹I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and ¹³¹I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative ¹³¹I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts.Conclusion: Similar to earlier studies, our results confirm that ¹³¹I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression.Abbreviations:CI = confidence intervalDTC = differentiated thyroid cancer¹⁸F-FDG = fluoro-18 fluorodeoxyglucoseFEF = forced expiratory flowFTC = follicular thyroid cancerFVC = forced vital capacityGR = granulocytesHb = hemoglobinHR = hazard ratio¹³¹I = iodine-131LN = lymph nodeOR = odds ratioOS = overall survivalPET/CT = positive positron emission tomography/computed tomographyPFS = progression-free survivalPT = partial thyroidectomyPTC = papillary thyroid cancerRAI = radioactive iodineRBC = red blood cellTg = thyroglobulinTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTT = total thyroidectomyWBC = white blood cellsWBS = whole body scan     

Evolving Approaches in Managing Radioactive Iodine-Refractory Differentiated Thyroid Cancer

ObjectiveTo discuss the approach to care of patients with advanced differentiated thyroid cancer (DTC), in particular those with radioactive iodine (RAI)-refractory disease, and the transition to systemic treatment.MethodsA PubMed search was conducted using the search terms “radioactive iodine-refractory, differentiated thyroid cancer and treatment” restricted to a 2000-2012 timeframe, English language, and humans. Relevant articles were identified from the bibliographies of selected references. Four patient cases are presented to illustrate the clinical course of RAI-refractory DTC.ResultsThe current standard of care for early stage DTC could include surgery, RAI in some cases, and thyroid hormone suppression. For advanced RAI-refractory DTC, clinical practice guidelines established by the National Comprehensive Cancer Network and the American Thyroid Association recommend, as one option, the use of systemic therapy, including kinase inhibitors. Numerous trials are underway to evaluate the clinical benefit of these targeted therapies.ConclusionPreliminary results are encouraging with respect to the clinical benefit of targeted systemic therapies. However, at present there is no consensus on the criteria that define RAI-refractory disease and the optimal timing for transition to systemic therapy. There remains a need to establish common criteria to enhance patient care and enable better comparison across clinical studies. (Endocr Pract. 2014;20:263-275)     

Patient Perspectives on the Extent of Surgery and Radioactive Iodine Treatment for Low-Risk Differentiated Thyroid Cancer

ObjectiveTo understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI).MethodsAn online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked “what if” scenarios on core topics, including AS, extent of surgery, and indications for RAI.ResultsSurvey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS.ConclusionPatient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.     

The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups

PurposeTo analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC).ResultsThe median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months.ConclusionsThe survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors.     

Autonomously Functioning Thyroid Nodules In Patients &#x003c;21 Years Of Age: The Rhode Island Hospital Experience From 2003&#x00C2;&#x20AC;&#x201C;2013

Objective: This study evaluates the clinical characteristics, workup, treatment, and outcomes of pediatric patients diagnosed with an autonomously functioning thyroid nodule (AFTN) in a large cohort of patients presenting for evaluation of a thyroid nodule. There are few prior studies on AFTN in pediatrics, with limited data on treatment and outcomes. Rates of malignancy in AFTN are perceived as low, but prior studies have varying reports.Methods: This is a retrospective chart review of patients less than 21 years of age at Rhode Island Hospital over an 11-year period (2003&#x00E2;&#x20AC;&#x201C;2013). We reviewed 354 charts, which yielded 242 patients with a diagnosis of thyroid nodule and 17 patients with AFTN.Results: The prevalence of AFTN in patients presenting with thyroid nodules was 7%. Mean age of patients was 15.8 years at diagnosis, and mean nodule size was 3.3 cm. There was female predominance. Thyroid-stimulating hormone levels were suppressed at diagnosis in 87% of patients. Six patients were treated with surgery, 5 patients with radioactive iodine therapy (RAI), 2 patients with medication, and 1 patient was observed without treatment. Three patients treated with RAI required subsequent treatment for hypothyroidism or continued hyperthyroidism. One patient had papillary thyroid carcinoma based on final surgical pathology.Conclusion: Our study found a higher prevalence of AFTN compared to the reported prevalence in adults. We concur with the new guidelines on management of thyroid nodules in recommending surgery for treatment of AFTN, based on the variability of outcomes after treatment with RAI.Abbreviations:AFTN = autonomously functioning thyroid noduleanti-TG = thyroglobulin antibodiesanti-TPO = thyroid peroxidase antibodiesFNA = fine-needle aspirationICD-9 = International Classification of Diseases, Ninth RevisionPTC = papillary thyroid carcinomaRAI = radioactive iodineT₃ = triiodothyronineT₄ = thyroxineTSH = thyroid-stimulating hormoneTSI = thyroid-stimulating immunoglobulin