Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves' Disease in Patients With Active Thyrotoxicosis.

OBJECTIVE: Graves' disease (GD) is caused by the stimulation of thyrotropin receptors by autoantibodies. We compared the diagnostic accuracy of the thyroid-stimulating immunoglobulin (TSI) bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) assay in differentiating GD from other causes of thyrotoxicosis. METHODS: We retrospectively evaluated 493 patients with thyrotoxicosis who were tested with the third-generation TSI and TBII assays simultaneously. Patients were classified according to the clinical, histopathologic, and imaging criteria into the following groups: positive reference group (PRG) (patients with GD), negative reference group (NRG) (patients without GD), and inconclusive group (patients without a definitive diagnosis). RESULTS: TSI and TBII assays were concordant in 88% of the cases and showed a strong positive correlation (rs = 0.844, P < .01). When analyzed collectively, TSI and TBII assays confirmed the diagnosis of GD in 79% of the PRG cases and excluded GD in 92.5% of patients in NRG. Combined TSI and TBII assays or TBII assay alone showed similar accuracy to the diagnosis of GD (81.4% and 77.5%, respectively). Tests in 40 of 191 patients in PRG were negative for both TSI and TBII assays, whereas 3 of 40 cases in NRG had at least 1 positive thyrotropin receptor antibody test. False-negative cases were associated with subclinical hyperthyroidism, normal radionuclide uptake, longer duration of thyrotoxicosis, and absence of goiter or Graves' ophthalmopathy. CONCLUSION: TSI and TBII assays showed similar performance in differentiating GD from other causes of thyrotoxicosis in a real-world sample of patients with active thyrotoxicosis. In combination, both tests showed little benefit compared with the TBII assay alone. Thyrotropin receptor antibody assay results should be carefully interpreted in patients with mild GD or longstanding disease.

Completion Thyroidectomy is Less Common Following Updated 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines recommended that low-risk, differentiated thyroid cancers (DTC) between 1 and 4 cm may be treated with thyroid lobectomy alone. We sought to determine the effect of these guideline changes on the rate of completion thyroidectomy (CT) for low-risk DTC and factors influencing surgical decision-making. METHODS: All patients from 2014 to 2018 who received an initial thyroid lobectomy at our institution with final pathology demonstrating DTC were included. Patients were divided into "pre" and "post" guideline cohorts (2014-2015 and 2016-2018, respectively). The rate of CT was compared between the two cohorts. Patient demographics and tumor characteristics were examined for association with CT. RESULTS: A total of 163 patients met study criteria: 63 patients in the 2014-2015 ("pre") and 100 in the 2016-2018 ("post") group. In the "pre" period, 41 (65.1%) patients received CT compared with 43 (43.0%) in the "post" period (p < 0.01)-a 34% decrease in the rate of completion surgery (p < 0.01). Of low-risk patients with DTC between 1 and 4 cm in size, 17 of 35 (48.6%) received CT in the "pre" period compared with 15 of 60 (25.0%) in the post period-a 48.6% decrease in the rate of completion surgery (p = 0.02). Greater tumor size, capsular invasion, and multifocality were associated with CT in low-risk "post" guideline patients (p < 0.05 for all). CONCLUSIONS: The rate of CT decreased significantly by 48.6% for low-risk patients with DTC between 1 and 4 cm, demonstrating recognition of the 2015 ATA guidelines. However, 25% of these patients underwent CT, suggesting additional factors influencing the decision for further treatment.

A potential diagnostic pitfall for hobnail variant of papillary thyroid carcinoma.

AIMS: Hobnail variant of papillary thyroid carcinoma (PTC) is an aggressive PTC subtype characterised by a hobnail cytomorphology. However, some classic PTC have a 'hobnail-like' cytomorphology associated with thick, hyalinised, variably oedematous fibrovascular cores that appears to be a form of ischaemic/degenerative atypia. METHODS AND RESULTS: We studied three cohorts to compare the histopathological characteristics and clinical outcome of 'hobnail-like' classic PTC and true hobnail variant of PTC: cohort 1, PTC consecutively resected between 2016 and 2017 (to assess frequency of 'hobnail-like' cytomorphology); cohort 2, 20 'hobnail-like' classic PTC resected between 2005 and 2007 (to assess clinical outcome); and cohort 3, seven true hobnail variant of PTC. A 'hobnail-like' cytomorphology was identified in 16% of consecutively resected PTC. Compared with true hobnail variant, 'hobnail-like' classic PTC occurred in younger patients (mean age 40 years versus 68 years, P < 0.001), were smaller tumours (mean tumour size 2.1 cm versus 4.4 cm, P < 0.001), had a lower rate of gross extrathyroidal extension (0% versus 71%, P < 0.001), had a lower proliferative rate (≥3 mitoses per 10 high-power fields seen in 0% versus 71%, P < 0.001; Ki67 index ≥5% in 0% versus 86%, P < 0.001), a lower rate of secondary pathogenic mutations (for cases with molecular data, 0% versus 100%, P = 0.0061) and improved survival (for cases with sufficient clinical outcome data, 10-year disease-free survival of 93% versus 0%, P = 0.0016). CONCLUSION: Classic PTC can show ischaemic/degenerative atypia that mimics the hobnail cytomorphology of true hobnail variant; however, these tumours lack aggressive histopathological features and pursue an indolent clinical course.

Reasons Associated with Total Thyroidectomy as Initial Surgical Management of an Indeterminate Thyroid Nodule.

BACKGROUND: Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules. METHODS: Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy. Medical records were reviewed for patient demographics, neck symptoms, nodule size, cytology, molecular test results, final histopathology, and additional PSFs influencing surgical management. Variables were analyzed to determine associations with the use of initial TT. Logistic regression analyses were performed to identify independent associations. RESULTS: Of 325 included patients, 182/325 (56.0%) had HT and 143/325 (44.0%) had TT. While patient age and sex, nodule size, and cytology result were not associated with initial treatment, five PSFs were associated with initial TT (p < 0.0001). These included contralateral nodules, hypothyroidism, fluorodeoxyglucose avidity on positron emission tomography scan, family history of thyroid cancer, and increased surgical risk. At least one PSF was present in 126/143 (88.1%) TT patients versus 47/182 (25.8%) HT patients (p < 0.0001). Multivariate logistic regression analysis demonstrated that these variables were the strongest independent predictor of TT (odds ratio 45.93, 95% confidence interval 18.80-112.23, p < 0.001). CONCLUSIONS: When surgical management of an indeterminate cytology thyroid nodule was performed, several PSFs were associated with a preference by surgeons and patients for initial TT, which may be useful to consider in making decisions on initial operative extent.

POSITIVE THYROTROPIN RECEPTOR ANTIBODIES IN PATIENTS WITH TRANSIENT THYROTOXICOSIS.

OBJECTIVE: Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility. METHODS: Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics. RESULTS: Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks). CONCLUSION: These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered. ABBREVIATIONS: cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine.

Long- versus short-interval follow-up of cytologically benign thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodules are common, and most are benign. Given the risk of false-negative cytology (i.e. malignancy), follow-up is recommended after 1-2 years, though this recommendation is based solely on expert opinion. Sonographic appearance may assist with planning, but is limited by large inter-observer variability. We therefore compared the safety and efficacy of long- versus short-interval follow-up after a benign initial aspiration, regardless of sonographic appearance. METHODS: This study evaluated all patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, between 1999 and 2010, with a cytologically benign nodule >1 cm and who had returned for follow-up sonographic evaluation. Despite standard clinical recommendations, variation in patient compliance resulted in variable follow-up intervals from time of initial aspiration to the first repeat evaluation. Main outcome measures included nodule growth, repeat fine needle aspiration (FNA), thyroidectomy, malignancy, and disease-specific mortality. RESULTS: We evaluated 1,254 patients with 1,819 cytologically benign nodules, with a median time to first follow-up of 1.4 years (range, 0.5-14.1 years). The longer the follow-up interval, the more nodules grew and the more repeat FNAs were performed (P <0.001). The most clinical meaningful endpoints of malignancy or mortality, however, did not differ between the various follow-up intervals. The risk of a thyroidectomy (usually because of compressive symptoms) increased when time to first follow-up exceeded >3 years (4.9% vs. 1.2%, P = 0.0001), though no difference in malignancy risk was identified (0.2-0.8%, P = 0.77). No (0%) thyroid cancer-specific deaths were identified in either cohort. CONCLUSIONS: While expert opinion currently recommends repeat evaluation of a cytologically benign nodule at 1-2 years, these are the first data to demonstrate that this interval can be safely extended to 3 years without increased mortality or patient harm. Nodule growth can be expected, though detection of malignancies is unchanged. While replication of these data in large prospective multicenter studies is needed, this extension in follow-up interval would reduce unnecessary visits and medical interventions for millions of affected patients worldwide, leading to healthcare savings. Please see related commentary article: http://dx.doi.org/10.1186/s12916-016-0559-9 and research article: http://dx.doi.org/10.1186/s12916-015-0419-z .

Thyroid function and cardiovascular disease risk factors in euthyroid adults: a cross-sectional and longitudinal study.

OBJECTIVE AND DESIGN: We explored the cross-sectional and longitudinal associations of thyroid function within the normal range with cardiovascular disease (CVD) risk factors and adiposity measures. PATIENTS AND MEASUREMENTS: A total of 3483 (50·4% women) participants for the cross-sectional CVD study and 1630 (41·2% women) participants for the cross-sectional body composition substudy were drawn from the Framingham Third Generation Exam 1; 2912 participants (50·1% women) for the longitudinal CVD study and 713 participants (35·9% women) for the longitudinal body composition substudy were drawn from the Framingham Third Generation Exams 1-2. Thyroid function was assessed by thyrotropin [thyroid-stimulating hormone (TSH)] and free thyroxine (fT4) concentrations within the reference range at Exam 1. The associations between thyroid function and CVD risk factors were modelled via multivariable-adjusted regression models. Multivariable adjustment included age, sex, current smoking, postmenopausal status and BMI. RESULTS: Cross-sectionally, higher TSH concentration was associated with increased odds of hypertriglyceridaemia [odds ratio (OR)=1·10], and higher BMI (ß = 0·19 kg/m2 ), total cholesterol (ß = 0·05 mmol/l), triglycerides (ß = 0·0006 mmol/l) and subcutaneous adipose tissue (SAT) volume (ß = 38·8 cm3 ) (all P < 0·05). Cross-sectionally, fT4 was inversely associated with metabolic and adiposity-related CVD risk factors, including obesity (OR = 1·17), hypertriglyceridaemia (OR = 1·09), BMI (ß = 0·42 kg/m2 ), total cholesterol (ß = 0·05 mmol/l), triglycerides (ß = 0·0002 mmol/l), visceral adipose tissue (VAT) volume (ß = -20·7 cm3 ) and attenuation (0·17 HU) and VAT/SAT ratio (ß = -0·01) (all P < 0·05). However, during 6·1 years of follow-up, baseline TSH and fT4 levels were not longitudinally associated with CVD risk factors and adiposity measures. CONCLUSIONS: Thyroid function within the normal range is cross-sectionally, but not longitudinally, associated with CVD risk factors and adiposity measures.

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

BACKGROUND: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. METHODS: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. RESULTS: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. CONCLUSIONS: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.

How are childhood thyroid nodules discovered: opportunities for improving early detection.

In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits.

Nonoperative, Active Surveillance of Larger Malignant and Suspicious Thyroid Nodules.

CONTEXT: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. OBJECTIVE: This work aimed to examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4 cm in diameter. METHODS: A retrospective review was conducted of all consecutive patients who underwent nonoperative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001 to 2021. We included patients with an initial ultrasound-fine-needle aspiration confirming either (a) Bethesda 5 or 6 cytology or (b) a "suspicious" Afirma molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. RESULTS: Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules 2 cm or larger. No patients were found to develop new-incident occurrence of lymph node or distant metastasis. One patient, however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start of nonoperative selection. A total of 21% of patients had an increase in maximum diameter more than 3 mm, while volume increase of 50% or greater was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. CONCLUSION: These data expand consideration of active surveillance of PTC in select patients with intrathyroidal suspected malignancy greater than 1 cm in diameter. Rescue surgery, if required at a later time point, appears effective.

Subacute granulomatous (de Quervain) thyroiditis: grayscale and color Doppler sonographic characteristics.

OBJECTIVES: To describe the sonographic characteristics of subacute granulomatous (De Quervain) thyroiditis. METHODS: We retrospectively identified all patients at our institution during the last 11 years who had thyroid sonography with findings suggestive of subacute granulomatous thyroiditis. We then reviewed clinical data and laboratory results to establish the clinical diagnosis. A final diagnosis of subacute granulomatous thyroiditis was made on the basis of clinical symptoms, suppressed thyrotropin, an elevated erythrocyte sedimentation rate, and/or reduced or absent radionuclide uptake while hyperthyroid. RESULTS: Our study population consisted of 35 patients. Twenty-seven patients (79.4%) met clinical criteria for subacute thyroiditis. Symptoms included neck pain in 26 of 27 patients with subacute thyroiditis. The erythrocyte sedimentation rate ranged from 22 to 101 mm/h. In 21 cases (77.8%), sonography revealed focal, poorly defined, nonovoid areas of decreased echogenicity. Findings were bilateral in 16 patients and unilateral in 5. In the remaining 6, the gland or an entire lobe was diffusely heterogeneous. Color Doppler interrogation was performed in 20 patients. Flow was decreased to the sonographically abnormal areas in 19 (95%) and slightly increased in 1 patient. In all 9 patients who underwent radionuclide scanning, focal defects or large areas of decreased or absent uptake were found during the time of suppressed thyrotropin. Enlarged lymph nodes were noted in 16 patients (59.3%). CONCLUSIONS: The positive predictive value of sonography for diagnosing subacute granulomatous thyroiditis is 79.4%. The most common sonographic appearance is poorly defined regions of decreased echogenicity with decreased vascularity in the affected areas.

Identifying and Predicting Diverse Patterns of Benign Nodule Growth.

CONTEXT: The natural history of benign thyroid nodules is typically characterized by slow growth and minimal risk of malignant transformation. Available data have, to date, been unable to elucidate the diversity of benign nodule growth patterns over time nor predictive of which patients follow which pattern. OBJECTIVE: We aimed to better define the diverse patterns of benign nodule behavior and their predictors. METHODS: We prospectively studied 389 consecutive patients with solitary, solid, cytologically benign thyroid nodules ≥1 cm and follow-up ultrasound for at least 4 years. Demographic, sonographic, biochemical data were collected at initial evaluation, and subsequent growth patterns were identified over the follow-up. Predictors of growth at initial evaluation and 3 years of follow-up were defined. RESULTS: The mean (±SD) follow-up was 7.7 (±2.7) years. Three distinct growth patterns were identified: A) stagnant nodules with average growth rate < 0.2 mm/year; B) slow-growing nodules with a rate 0.2 to 1.0 mm/year; and C) fast-growing nodules increasing > 1.0 mm/year. Fast-growing nodules represented 17.2% of the cohort, and were more frequent in patients younger than 50 years (OR 2.2 [1.2-4.1], P = 0.016), and in larger nodules (2.0-2.9 cm, OR 3.5 [1.7-7.1], P = 0.001; >3.0 cm, OR 4.4 [1.8-10.4], P = 0.001 vs reference 1-1.9 cm). In a multiple regression model, nodule growth at 3 years at an average growth rate over 0.2 mm/year over 3 years since initial evaluation was an independent predictor of longer-term fast nodule growth, even after adjusting for age, biological sex, TSH level, and nodule size (P < 0.001). CONCLUSION: The natural history of benign nodule growth is diverse, with over 80% of nodules demonstrating minimal to no growth long-term. Nearly 20% of cytologically benign nodules may exhibit a fast, continued growth pattern, which can be predicted by the 3-year growth rate pattern. These findings can help inform decision making for tailored benign nodule follow-up and monitoring.

Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.

PURPOSE: RAS mutations occur across the spectrum of thyroid neoplasms, and more tools are needed for better prognostication. The objective of this study was to evaluate how additional genetic events affecting key genes modify prognosis in patients with RAS-mutant thyroid cancers, and specifically differentiated thyroid cancers (DTC). EXPERIMENTAL DESIGN: We performed a clinical-genomic analysis of consecutive patients with DTC, poorly differentiated (PDTC), or anaplastic thyroid cancer (ATC) between January 2014 and December 2021, in whom a custom-targeted next-generation sequencing assay was performed. Patients harboring RAS mutations were included, and we compared their clinical features and outcomes based upon the presence of additional oncogenic alterations. RESULTS: Seventy-eight patients were identified, with 22% (17/78) harboring a driver RAS mutation plus an additional oncogenic alteration. All six (100%) ATCs had an additional mutation. Compared with DTCs harboring a solitary RAS mutation, patients with DTC with RAS and additional mutation(s) were more likely to be classified as American Thyroid Association high-risk of recurrence (77% vs. 12%; P < 0.001) and to have larger primary tumors (4.7 vs. 2.5 cm; P = 0.002) and advanced stage (III or IV) at presentation (67% vs. 3%; P < 0.001). Importantly, over an average 65-month follow-up, DTC-specific-mortality was more than 10-fold higher (20% vs. 1.8%; P = 0.011) when additional mutations were identified. CONCLUSIONS: Identification of key additional mutations in patients with RAS-mutant thyroid cancers confers a more aggressive phenotype, increases mortality risk in DTC, and can explain the diversity of RAS-mutated thyroid neoplasia. These data support genomic profiling of DTCs to inform prognosis and clinical decision-making.

Papillary Thyroid Carcinomas with Tall Cell Features: An Intermediate Entity Between Classic and Tall Cell Subtypes.

Background: While the diagnosis of papillary thyroid carcinomas (PTCs) with tall cell features (PTCtcf) is often made for carcinomas with histological features intermediate between classic and tall cell subtypes of PTC (tcPTC), its comparative signature to that of either tcPTC or classic PTC is less clear. The objective of this study was to perform an integrative clinicopathologic and genomic analysis elucidating the spectrum of tcPTC, PTCtcf, and classic PTC. Methods: We analyzed all consecutive patients with tcPTC and PTCtcf evaluated at a tertiary academic referral center between 2005 and 2020, as well as a comparative cohort of classic PTC, in a retrospective observational cohort analysis. Clinicopathologic data were compared among the three groups, including progression-free survival (PFS), recurrent/persistent disease, and a negative composite outcome of death, progression, or need for advanced therapy. To specifically understand differences between tcPTC and PTCtcf, targeted next-generation sequencing was performed in a subset of these cohorts. Results: A total of 292 patients were analyzed (81 tcPTC, 65 PTCtcf, 146 classic PTC). Thirteen percent of tcPTC versus 8% of PTCtcf versus 1% of classic PTC had the advanced American Joint Committee on Cancer stage (p = 0.002). Similarly, macroscopic extrathyroidal extension was observed in 38% of tcPTC, 14% of PTCtcf, and 12% of classic PTC (p < 0.001). The 5-year PFS was 76.5%, 81.5%, and 88.3% for tcPTC, PTCtcf, and classic PTC, respectively, while the rates of the negative composite outcome 40.2% for tcPTC, 20.7% for PTCtcf, and 11.2% for classic PTC (p < 0.001). In a multivariable Cox regression analysis, the negative composite outcome was independently associated with tcPTC (HR 4.3 [confidence interval 1.1-16.1], p = 0.03). tcPTC demonstrated substantially more hotspot TERT promoter mutations than PTCtcf (44% vs. 6%, p = 0.012). Conclusions: Our study demonstrates a continuum of disease-specific risk of PTC, pointing at PTCtcf as an intermediate entity between tcPTC and classic PTC. These data provide a more refined understanding of risk at time of presentation, while better elucidating the diversity of genomic drivers.

Clinical experience following implementation of routine SPECT-CT imaging following 131-iodine administration for thyroid cancer.

Background: Planar scintigraphy has long been indicated in patients receiving I-131 therapy for thyroid cancer to determine the anatomic location of metastases. We studied our experience upon implementing additional single-photon emission (SPECT)-CT scanning in these patients. Method: We performed a retrospective study of consecutive adult patients with newly diagnosed thyroid cancer treated with I-131 between 2011 and 2017. Radiologic findings detected with planar scintigraphy alone vs those identified with SPECT-CT scanning were primary endpoints. Result: In this study, 212 consecutive patients with thyroid cancer were analyzed in two separate cohorts (107 planar scintigraphy alone and 105 planar scintigraphy with SPECT-CT). The addition of SPECT-CT resulted in more findings, both thyroid-related and incidental. However, we identified only 3 of 21 cases in which SPECT-CT provided an unequivocal additional benefit by changing clinical management beyond planar scintigraphy alone. No difference in the detection of distant metastatic disease or outcome was identified between cohorts. Conclusion: Synergistic SPECT-CT imaging in addition to planar nuclear scintigraphy adds limited clinical value to thyroid cancer patients harboring a low risk of distant metastases, while frequently identifying clinically insignificant findings. These data from a typical cohort of patients receiving standard thyroid cancer care provide insight into the routine use of SPECT-CT in such patients.

Point of Care Measurement of Body Mass Index and Thyroid Nodule Malignancy Risk Assessment.

Background: Large scale epidemiology studies have suggested obesity may increase the risk of thyroid cancer, though no prospective analyses using real-world measurement of BMI at a time proximate to initial thyroid nodule evaluation have been performed. Methods: We performed a prospective, cohort analysis over 3 years of consecutive patients presenting for thyroid nodule evaluation. We measured BMI proximate to the time of initial evaluation and correlated this with the final diagnosis of benign or malignant disease. We further correlated patient BMI with aggressivity of thyroid cancer, if detected. Results: Among 1,259 consecutive patients with clinically relevant nodules, 199(15%) were malignant. BMI averaged 28.6 kg/m2 (SD: 6.35, range:16.46-59.26). There was no correlation between the measurement of BMI and risk of thyroid cancer (p=0.58) as mean BMI was 28.9 kg/m2 and 28.6 kg/m2 in cancerous and benign cohorts, respectively. Similarly, BMI did not predict aggressive thyroid cancer (p=0.15). While overall nodule size was associated with increased BMI (p<0.01), these data require further validation as obesity may hinder nodule detection until large. Conclusion: In contrast to findings published from large scale association studies drawn from national databases, these prospective data of consecutive patients presenting for nodule evaluation detect no association of obesity (as measured by BMI) with thyroid cancer. Real time measurement of BMI at the time of thyroid nodule evaluation does not contribute to cancer risk assessment.

Thyroid Nodule Shape Independently Predicts Risk of Malignancy.

CONTEXT: Predictive models of thyroid nodule cancer risk are presently based upon nodule composition, echogenicity, margins, and the presence of microcalcifications. Nodule shape has shown promise to be an additive factor helping determine the need for nodule biopsy. OBJECTIVE: We sought to determine if calculation of a nodule's spherical shape independently associates with cancer risk. METHODS: This prospective cohort study, conducted at a single large academic healthcare system in the United States, included patients with 1 or 2 clinically relevant thyroid nodules (predominantly solid and over 1 cm) presenting for diagnostic evaluation. Thyroid ultrasound, cytological evaluation with fine-needle biopsy, and/or histopathological examination on occasion of thyroid surgery were performed. We calculated the nodule's long to short ratio (spherical shape), and its association with tissue proven benign or malignant endpoints. RESULTS: The long to short nodule ratio was significantly lower in malignant compared to benign nodules indicating greater risk of malignancy in more spherical nodules (1.63 ±â€…0.38 for malignant nodules vs 1.74 ±â€…0.47 for benign, P < 0.0001). The risk of malignancy continually increased as the long to short ratio approached a purely spherical ratio of 1.0 (ratio > 2.00, 14.6% cancer; ratio 1.51-2.00, 19.7%; ratio 1.00-1.50, 25.5%, P < 0.0001). In multiple regression analysis, younger age, male sex, and nodule's spherical shape were each independently associated with cancer risk. CONCLUSION: The more a thyroid nodule is spherically shaped, as indicated by a long to short ratio approaching 1.0, the greater its risk of malignancy. This was independent of age, sex, and nodule size. Incorporating a nodule's sphericity in the risk stratification systems may improve individualized clinical decision making.