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Background: Before the development of antithyroid drugs in the 1940s, treatment of Graves' hyperthyroidism was primarily surgical. Surgical mortality was quite variable, but a significant minority of patients died during or after surgery. Summary: In 1936, Karl Compton, President of the Massachusetts Institute of Technology, in a lecture attended by Massachusetts General Hospital physicians, suggested that artificially radioactive isotopes might be useful for studying metabolism. By 1942, Hertz and Roberts reported on the successful use of radioactive iodine (RAI) to treat Graves' hyperthyroidism. RAI uptake was subsequently demonstrated in well-differentiated thyroid cancer metastases. In 1948, Seidlin demonstrated stimulation of uptake in thyroid cancer metastases by thyrotropin (TSH). By 1990, 69% of endocrinologists in North America recommended RAI for Graves' hyperthyroidism. Currently RAI is less frequently used for Graves' hyperthyroidism, related to concerns about exacerbation of thyroid eye disease, about radiation exposure, and about potential adverse consequences of permanent hypothyroidism. Similarly, RAI was administered to the majority of patients with thyroid cancer for decades, but its use is now more selective. Conclusions: RAI is a remarkable example of interinstitutional cooperation between physicians and scientists to transition from bench to bedside in only three years. It is the model for a theranostic approach to disease (the simultaneous use of a radioactive drug for diagnosis and therapy). The future of RAI is less certain; inhibition of TSH receptor stimulating antibodies in Graves' disease and more precise targeting of genes that drive thyroid oncogenesis may diminish the use of RAI. Alternatively, redifferentiation techniques may improve the efficacy of RAI in RAI-refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6–42 million in cost savings over a five-year period for these patients, and incremental 54–370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification. [ABSTRACT FROM AUTHOR]

Background: The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. Methods: We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later. Data were descriptively summarized, after excluding missing responses. Results: The overall response rate was 19.8% (348/1761). The effective response rate was 20.2% (348/1720), after excluding a recently deceased member and individuals who had either invalid e-mail addresses or whose e-mails were returned. Of the respondents, 37.9% (132/348) were female, 60.4% (209/346) were endocrinologists, 27.5% (95/346) were surgeons, and 3.5% (12/346) were nuclear medicine specialists. The majority of respondents (71.9%; 250/348) were at a mid- or advanced-career level, and more than half were in academia (57.5%; 195/339). The majority (69.8%; 243/348) practiced in North America. The vast majority of respondents indicated that the CPGs explained the underlying evidence (92.3%; 298/323) and 92.9% (300/323) agreed or strongly agreed with the content. Most respondents stated that they regularly used the CPGs in their practice (83.0%; 268/323). Most respondents (83.0%; 268/323) also agreed or strongly agreed that the recommendations were easy to incorporate in their practice. The most popular CPG format was an electronic desktop file (78.8%; 252/320). Shorter more frequent CPGs were favored by 55.0% (176/320) of respondents, and longer traditional CPGs were favored by 39.7% (127/320). Conclusions: The clinical content and evidence explanations in the adult TN and DTC CPGs are widely accepted and applied among ATA survey respondents. Future ATA CPG updates need to be optimized to best meet users' preferences regarding format, frequency, and length. [ABSTRACT FROM AUTHOR]

Background: Aberrations involving the ROS1 gene have not been reported in thyroid cancer. Here, a case of ROS1-associated thyroid cancer with unique and aggressive characteristics is presented. Patient findings: A 24-year-old athlete presented with a 3.5 cm left paramedian upper neck mass. Open biopsy demonstrated a papillary thyroid carcinoma arising in the pyramidal lobe. Additional imaging revealed involvement of her cricothyroid membrane, thyroid laryngeal cartilage, and left vocal cord. Complete en bloc surgical resection of the thyroid with cricothyroid membrane and endolarynx was performed with negative surgical margins. Microscopically, the tumor was largely solid with microfollicular architecture with focal cytoplasmic clearing and nodular invasion with rare true papillae, extending posteriorly through the cricothyroid membrane into the deep soft tissue of the left anterior vocal cord (pT4a). Metastases were present in 5/11 lateral neck and pretracheal lymph nodes with a size up to 0.4 cm (pN1b) with perinodal lymphatic involvement. She was staged according to her age (<45 years) as stage I. The solid-variant histology and locally aggressive behavior triggered oncologic genotyping, which was performed using massive parallel sequencing and anchored multiplexed next-generation sequencing for gene fusion detection on formalin-fixed paraffin embedded tissue. Targeted genotyping did not reveal a panel-specific point mutation. However, gene fusion assessment demonstrated a gene fusion involving ROS1. Mapping of the fusion and sequence analysis identified CCDC30 as the ROS1 fusion partner. Sequence-based prediction of the fusion product revealed the coiled-coil domain 30 (CCDC30) gene fused to the N-terminal ROS1 kinase domain, with CCDC30 as the postulated driver of ROS1-kinase constitutive activation. ROS1 rearrangement was confirmed using fluorescent in situ hybridization as an orthogonal method. A review of all currently reported ROS1 fusions in >7000 samples (The Cancer Genome Atlas) showed no prior report of ROS1-CCDC30, ROS1 fusions, or presence of ROS1 aberrations in thyroid cancer. Summary: Herein, the first case of a ROS1 rearrangement in a papillary thyroid carcinoma with a locally aggressive presentation is reported. Conclusion: A review of additional patients with solid-variant papillary thyroid carcinoma and similar clinical characteristics with undetermined tumor genetics is needed, especially in light of the availability of ROS1- targeted therapeutics. [ABSTRACT FROM AUTHOR]

Background: Health registries have become extremely powerful tools for cancer research. Unfortunately, certain details and the ability to adapt to new information are necessarily limited in current registries, and they cannot address many controversial issues in cancer management. This is of particular concern in differentiated thyroid cancer, which is rapidly increasing in incidence and has many unknowns related to optimal treatment and surveillance recommendations. Summary: In this study, we review different types of health registries used in cancer research in the United States, with a focus on their advantages and disadvantages as related to the study of thyroid cancer. This analysis includes population-based cancer registries, health systems-based cancer registries, and patient-based disease registries. It is important that clinicians understand the way data are collected in, as well as the composition of, these different registries in order to more critically interpret the clinical research that is conducted using that data. In an attempt to address shortcoming of current databases for thyroid cancer, we present the potential of an innovative web-based disease management tool for thyroid cancer called the Thyroid Cancer Care Collaborative (TCCC) to become a patient-based registry that can be used to evaluate and improve the quality of care delivered to patients with thyroid cancer as well as to answer questions that we have not been able to address with current databases and registries. Conclusion: A cancer registry that follows a specific patient, is integrated into physician workflow, and collects data across different treatment sites and different payers does not exist in the current fragmented system of healthcare in the United States. The TCCC offers physicians who treat thyroid cancer numerous time-saving and quality improvement services, and could significantly improve patient care. With rapid adoption across the nation, the TCCC could become a new paradigm for database research in thyroid cancer to improve our understanding of thyroid cancer management. [ABSTRACT FROM AUTHOR]

Background: Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC. Methods: This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with 131I (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were 131I uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival. Results: After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T-Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group ( p<0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease ( p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL were found in 87.5% of the RAI-L-ABL group ( n=28), 86.3% of the C-Tx group ( n=57), and 77.8% of the T-Tx group ( n=21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups ( p<0.05, between groups). Conclusions: RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of >25 mIU/L and preparing patients for conventional 131I treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common after RAI-L-ABL. [ABSTRACT FROM AUTHOR]

The article describes the case of a teenage girl who presented an enlarging neck mass in a pediatric endocrinology clinic. Aside from the physical symptom of neck swelling, the patient also complained of occasional nausea and neck tightness. Details about her clinical background are discussed, noting that her family has a history of hypothyroidism. Surgical treatment has been recommended following the detection of a papillary thyroid carcinoma within the right isthmus of the thyroid of the patient.

Background: To detect recurrent disease in patients who have had differentiated thyroid cancer, periodic withdrawal of thyroid hormone therapy may be required to raise serum thyrotropin concentrations to stimulate thyroid tissue so that radioiodine (iodine-131) scanning can be performed. However, withdrawal of thyroid hormone therapy causes hypothyroidism. Administration of recombinant human thyrotropin stimulates thyroid tissue without requiring the discontinuation of thyroid hormone therapy. Methods: One hundred twenty-seven patients with thyroid cancer underwent whole-body radioiodine scanning by two techniques: first after receiving two doses of thyrotropin while thyroid hormone therapy was continued, and second after the withdrawal of thyroid hormone therapy. The scans were evaluated by reviewers unaware of the conditions of scanning. The serum thyroglobulin concentrations and the prevalence of symptoms of hypothyroidism and mood disorders were also determined. Results: Sixty-two of the 127 patients had positive whole-body radioiodine scans by one or both techniques. The scans obtained after stimulation with thyrotropin were equivalent to the scans obtained after withdrawal of thyroid hormone in 41 of these patients (66 percent), superior in 3 (5 percent), and inferior in 18 (29 percent). When the 65 patients with concordant negative scans were included, the two scans were equivalent in 106 patients (83 percent). Eight patients (13 percent of those with at least one positive scan) were treated with radioiodine on the basis of superior scans done after withdrawal of thyroid hormone. Serum thyroglobulin concentrations increased in 15 of 35 tested patients: 14 after withdrawal of thyroid hormone and 13 after administration of thyrotropin. Patients had more symptoms of hypothyroidism (P<0.001) and dysphoric mood states (P<0.001) after withdrawal of thyroid hormone than after administration of thyrotropin. Conclusions: Thyrotropin stimulates radioiodine uptake for scanning in patients with thyroid cancer, but the sensitivity of scanning after the administration of thyrotropin is less than that after the withdrawal of thyroid hormone. Thyrotropin scanning is associated with fewer symptoms and dysphoric mood states. (N Engl J Med 1997;337:888-96.) [ABSTRACT FROM AUTHOR]