Implementing Key Changes in The American Thyroid Association 2015 Thyroid Nodules/Differentiated Thyroid Cancer Guidelines Across Practice Types

Objective: This article provides suggestions to help clinicians implement important changes in the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma (“ATA 2015”) across diverse settings.Methods: Key ATA 2015 changes are summarized regarding: (1) thyroid nodule management; (2) lobectomy versus thyroidectomy for differentiated thyroid carcinoma (DTC); and (3) surveillance following primary treatment of DTC. Advice to facilitate implementation is based on clinical experience and selected literature.Results: Strategies are described to enhance acquisition of high-quality information that helps identify patients who may possibly avoid fine-needle aspiration (FNA) of thyroid nodules or total thyroidectomy for DTC, or undergo less intense postoperative surveillance. Sonographic imaging of nodules may improve if sonograms are obtained by clinicians ordering or performing FNA or trusted high-volume sonographers. Cytopathologic assessment and reporting can be improved by working with regional or national experts. Pre-operative evaluation by endocrinologists is important so that patients are referred to experienced, proficient surgeons and assisted with well-informed decision-making regarding surgical radicality. Endocrinologists and surgeons should ensure performance of pre-operative neck ultrasonography, voice/laryngeal evaluation, and contrast-enhanced cross-sectional imaging when appropriate. Findings should be disseminated to all healthcare team members, ideally through a comprehensive medical record accessible to the entire team.Conclusion: Optimization of the sequence of specialist visits and assembly of interactive multidisciplinary teams coupled with intensified interdisciplinary and patient communication may enable clinicians to more effectively implement ATA 2015, which calls for more individualized, and often, less “invasive” management of thyroid nodules and DTC.Abbreviations: ATA 2009 = 2009 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; ATA 2015 = 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; DTC = differentiated thyroid carcinoma; FNA = fine-needle aspiration; PET/CT = positron emission tomography/computed tomography     

Serial Neck Ultrasound is More Likely to Identify False-Positive Abnormalities than Clinically Significant Disease in Low-Risk Papillary Thyroid Cancer Patients

Objective: American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery.Methods: We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence.Results: Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2–17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6–4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease.Conclusion: In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.Abbreviations:18FDG-PET = 18-fluorodeoxyglucose-positron emission testingAJCC = American Joint Committee on CancerATA = American Thyroid AssociationCT = computed tomographyETA = European Thyroid AssociationMRI = magnetic resonance imagingPTC = papillary thyroid cancerRAI = radioactive iodineTg = thyroglobulinTgAb = antithyroglobulin antibodiesTSH = thyroid-stimulating hormoneUS = ultrasound     

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     

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 [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 [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     

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     

Risk of Malignancy in Thyroid Cytology: The Impact of The Reclassification of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)

Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients.Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012–2014 and selected category III (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS]), IV (follicular neoplasm [FN]/suspicious for a follicular neoplasm [SFN]), V (suspicious for malignancy [SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category.Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine.Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V.Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm     

Utility of Afirma Gene Expression Classifier for Evaluation of Indeterminate Thyroid Nodules and Correlation with Ultrasound Risk Assessment: Single Institutional Experience

Objective: We assessed our experience with Afirma gene expression classifier (GEC) combined with sono-graphic risk assessment, using both the American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TI-RADS) in evaluating indeterminate thyroid nodules.Methods: We identified 98 patients with 101 nodules who had a second fine needle aspiration biopsy (FNA) between January 1, 2014, and September 30, 2017, and sent to Veracyte for cytopathology and subsequent Afirma GEC testing. A second FNA biopsy was performed if the initial cytopathology was either Bethesda III or IV (n = 94) or nondiagnostic (n = 7). We correlated cytopathology, histopathology, and Afirma GEC results with sonographic risk assessment using both the ATA system and TI-RADS.Results: The mean age of the cohort was 57.4 ± 12.3 years; 84% women and 60% white. Repeat FNA was benign in 51 of 101 nodules, and of the remaining 50 nodules, 18 (36%) were GEC-benign and 32 (64%) GEC-suspicious. Eighteen of the 32 GEC-suspicious nodules underwent surgery with the following results: 7 benign (39%), 1 follicular thyroid carcinoma (6%), 6 follicular variant of papillary thyroid cancer (33%), and 4 noninvasive follicular tumor with papillary-like nuclear features (22%). The malignancy rate among the surgical cohort was 39% (without noninvasive follicular tumor with papillary-like nuclear features [NIFTP]) and 61% (with NIFTP) and about 50% and 20% of this group scored in the high suspicion category by ATA and TR5 by TI-RADS, respectively.Conclusion: Afirma GEC was useful in avoiding surgery in one-third of indeterminate nodules and performed similarly to ATA and TI-RADS. However, the use of echogenicity in scoring may underestimate the risk of malignancy in patients with indeterminate nodules.Abbreviations:ATA = American Thyroid Association; AUS = Atypia of Undetermined Significance; FLUS = Follicular Lesion of Undetermined Significance; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid cancer; GEC = Gene Expression Classifier; ND = nondiagnostic; NIFTP = noninvasive follicular tumor with papillary-like nuclear features; TI-RADS = Thyroid Imaging Reporting and Data System; TR = TI-RADS     

Using the Ata and Acr Ti-Rads Sonographic Classifications as Adjunctive Predictors of Malignancy for Indeterminate Thyroid Nodules

Objective: Thyroid nodules with indeterminate cytology pose management challenges in clinical practice. The aim of this study was to determine the efficacy of ultrasound features in navigating clinical decision making in thyroid nodules with indeterminate cytology.Methods: We retrospectively reviewed ultrasound imaging from 186 adult patients with thyroid nodules and indeterminate cytology who underwent thyroidectomy at a quaternary hospital from 2010–2017. All nodules were classified based on the American Thyroid Association (ATA) and 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Nodules were included if good quality pre-operative ultrasound imaging and surgical pathology were available.Results: A total of 202 thyroid nodules were included. The median age was 57 years; 82.8% were female. Risk of malignancy (ROM) in resected nodules with Bethesda 3 and 4 cytology was 19.4% and 30.3%, respectively. ATA high-suspicious and TI-RADS 5 nodules had high ROM, 100% in both systems for Bethesda 3 nodules; 66.7% and 50.0%, respectively, for Bethesda 4 nodules. For ATA very-low suspicious/TI-RADS 1 and 2, ROM was 0%. ROM in ATA low-suspicious/TI-RADS 3 nodules with Bethesda 3 cytology was lower (15.2% and 16.0%, respectively) than Bethesda 4 cytology (33.8% and 34.3%, respectively). ATA intermediate-suspicious/TI-RADS 4 nodules with Bethesda 4 cytology had a lower ROM (11.1% and 18.2%, respectively) than Bethesda 3 cytology (28.6 % and 31.6%, respectively).Conclusion: Using either the ATA or the TI-RADS system to risk-stratify nodules with indeterminate cytology may help clinicians plan better for additional diagnostic testing and treatment.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; AUS = atypia of undetermined significance; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; PPV = positive predictive value; ROM = risk of malignancy; SFN = suspicious for follicular neoplasm; TI-RADS = Thyroid Imaging Reporting and Data System     

Prognostic Value of Lymph Node Uptake on Pretreatment F-18 FDG PET/CT in Patients with N1B Papillary Thyroid Carcinoma

Objective: The aim of this study was to investigate the prognostic value of metabolic characteristics of metastatic lymph node (LN) using pretreatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for patients with papillary thyroid carcinoma (PTC) and metastatic lateral LN (N1b).Methods: Ninety-six PTC patients (female:male = 72:24; median age, 44.5 years) with pathologic N1b who underwent pretreatment FDG PET/CT, total thyroidectomy, and radioactive iodine ablation were retrospectively reviewed. To predict responses to initial therapy and recurrence, clinicopathologic factors and metabolic parameters were reviewed, such as sex, age, tumor size, extranodal extension, number and ratio of metastatic LNs, serum thyroglobulin, and maximum standardized uptake value (SUVmax).Results: Among the 96 PTC patients, 81 (84.4%) were classified into the acceptable response (58 excellent; 23 indeterminate) and 15 (15.6%) into the incomplete response (8 biochemical incomplete; 7 structural incomplete) by the 2015 American Thyroid Association management guideline for differentiated thyroid carcinoma. The multivariate analysis showed that SUVmax of N1b (P = .018), pre-ablation stimulated thyroglobulin level (P = .006), and the ratio of metastatic LNs (P = .018) were related to incomplete response. The cutoff value of each variable was determined by receiver operating characteristic analysis. Nine (9.4%) patients experienced recurrences (median follow-up: 50 months). The Kaplan-Meier analysis revealed that SUVmax of N1b (cutoff value: 2.3; P = .025) and ratio of metastatic LNs (cutoff value: 0.218; P = .037) were significant prognostic factors for recurrence.Conclusion: High SUVmax of N1b cervical LN on pretreatment FDG PET/CT could predict incomplete responses to initial therapy and recurrence in patients with N1b PTC.Abbreviations: ATA = American Thyroid Association; DTC = well-differentiated thyroid carcinoma; FDG = F-18 fluorodeoxyglucose; IQR = interquartile range; LN = lymph node; N1b = metastatic lateral cervical lymph node; PET/CT = positron emission tomography/computed tomography; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SUVmax = maximum standardized uptake value; Tg = thyroglobulin; USG = ultrasonography     

Autonomously Functioning Thyroid Nodules In Patients <21 Years Of Age: The Rhode Island Hospital Experience From 2003€“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 (2003–2013). 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     

Incidence,Risk Factors,and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma

Objective: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma.Methods: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2.Results: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism.Conclusion: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2.Abbreviations: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic     

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

Objective: This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP).Methods: This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer–specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared.Results: The mean ages of patients in the AS and OP groups were 58.6 ± 12.5 and 58.4 ± 13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about “voice” (P<.001), “psychological” (P =.025), “problems with scar” (P<.001), and “gained weight” (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group.Conclusion: PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology.Abbreviations: AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer–specific health-related quality of life; TSH = thyrotropin     

Sonographic Features Of Multifocal Papillary Thyroid Carcinomas

Objective: It is uncertain whether papillary thyroid carcinomas (PTCs) of the same subtype display similar sonographic features. This retrospective analysis of pre-operative sonographic and pathologic findings aimed to assess whether PTCs of the same subtype share sonographic features.Methods: Before undergoing thyroid surgery, 137 patients underwent ultrasound (US) examination. A single radiologist used a picture archiving and communication system and pathologic reports to investigate all sonographic features of the largest and second largest PTCs. Additionally, the radiologist evaluated the similarity of sonographic features between primary (largest), secondary (second largest), and daughter (secondary with same subtype as the primary) PTCs.Results: Of the 137 PTC patients, 48 (35.0%) had multiple PTCs; however, 5 had no US images of the secondary PTC. Of the 43 secondary PTCs with US images, 9 (20.9%) secondary PTCs were of a different subtype than the primary PTC and revealed sonographic features that differed from those of the primary PTC. Of the 48 patients with multiple PTCs, the subtype was the same in the primary and secondary PTCs in 34 (70.8%) patients. Of the 34 daughter PTCs, 32 (94.1%) had sonographic features similar to those of the primary PTC, whereas 2 (5.9%) showed different sonographic features than the primary PTC. There was no significant difference between primary and daughter PTCs in the size, location, sonographic features, or Korean Thyroid Imaging Reporting and Data System category (P>.05).Conclusion: Daughter PTCs show similar sonographic features as the primary PTC.Abbreviations: K-TIRADS = Korean Thyroid Imaging Reporting and Data System; PTC = papillary thyroid carcinoma; US = ultrasound     

Is it Worth Suppressing Tsh in low- and Intermediate-Risk Papillary Thyroid Cancer Patients Before the First Disease Assessment?

Objective: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment.Methods: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL.Results: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups.Conclusion: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography     

National Survey of Endocrinologists and Surgeons Regarding Active Surveillance for Low-Risk Papillary Thyroid Cancer

ObjectiveActive surveillance for low-risk papillary thyroid cancer (PTC) was endorsed by the American Thyroid Association guidelines in 2015. The attitudes and beliefs of physicians treating thyroid cancer regarding the active surveillance approach are not known.MethodsA national survey of endocrinologists and surgeons treating thyroid cancer was conducted from August to September 2017 via professional society emails. This mixed-methods analysis reported attitudes toward potential factors impacting decision-making regarding active surveillance, beliefs about barriers and facilitators of its use, and reasons why physicians would pick a given management strategy for themselves if they were diagnosed with a low-risk PTC. Survey items about attitudes and beliefs were derived from the Cabana model of barriers to guideline adherence and theoretical domains framework of behavior change.ResultsAmong 345 respondents, 324 (94%) agreed that active surveillance was appropriate for at least some patients, 81% agreed that active surveillance was at least somewhat underused, and 76% said that they would choose surgery for themselves if diagnosed with a PTC of ≤1 cm. Majority of the respondents believed that the guidelines supporting active surveillance were too vague and that the current supporting evidence was too weak. Malpractice and financial concerns were identified as additional barriers to offering active surveillance. The respondents endorsed improved information resources and evidence as possible facilitators to offering active surveillance.ConclusionAlthough there is general support among physicians who treat low-risk PTC for the active surveillance approach, there is reluctance to offer it because of the lack of robust evidence, guidelines, and protocols.     

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     

Historical and Current Perspective in the Use of Thyroid Extracts for the Treatment of Hypothyroidism

Objective: To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies.Methods: A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature.Results: A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products.Conclusion: The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.Abbreviations: AACE = American Association of Clinical Endocrinologists ATA = American Thyroid Association BMR = basal metabolic rate FDA = Food and Drug Administration FT4 = free thyroxine 131-I = radioactive iodine 131 LT3 = liothyronine LT4= levothyroxine NDA = new drug application PBI = proteinbound iodine T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone TT3 = total triiodothyronine USP = U.S. Pharmacopeia     

Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology

Objective: The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy.Methods: A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology.Results: In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%.Conclusion: Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value.Abbreviations:BRAF = v-raf murine sarcoma viral oncogene homolog B1FLUS = follicular lesion of undetermined significanceFNAB = fine-needle aspiration biopsyFTC = follicular thyroid carcinomaHRAS = homologous to the oncogene from the Harvey rat sarcoma virusKRAS = homologous to the oncogene from the Kirsten rat sarcoma virusNRAS = first isolated from a human neuroblastoma/neuroblastomaRAS = viral oncogene homologPAX8 = paired box 8PCR = polymerase chain reactionPPAR-gamma = peroxisome proliferator-activated receptor gammaPTC = papillary thyroid carcinomaRAS = rat sarcomaRET = rearranged during transfection tyrosine-kinase proto-oncogeneSM = somatic mutationSNP = single-nucleotide polymorphism