Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier.

Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier.

Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

Purpose: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies.

Methods: We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date.

Real-time quantitation of thyroidal radioiodine uptake in thyroid disease with monitoring by a collar detection device.

Radioactive iodine (RAI) is safe and effective in most patients with hyperthyroidism but not all individuals are cured by the first dose, and most develop post-RAI hypothyroidism. Postoperative RAI therapy for remnant ablation is successful in 80-90% of thyroid cancer patients and sometimes induces remission of nonresectable cervical and/or distant metastatic disease but the effective tumor dose is usually not precisely known and must be moderated to avoid short- and long-term adverse effects on other tissues. The Collar Therapy Indicator (COTI) is a radiation detection device embedded in a cloth collar secured around the patient's neck and connected to a recording and data transmission box.

Afirma Genomic Sequencing Classifier and Xpression Atlas Molecular Findings in Consecutive Bethesda III-VI Thyroid Nodules.

Context: Broad genomic analyses among thyroid histologies have been described from relatively small cohorts.

Objective: Investigate the molecular findings across a large, real-world cohort of thyroid fine-needle aspiration (FNA) samples.

Design: Retrospective analysis of RNA sequencing data files.

The prostate-specific membrane antigen (PSMA)-targeted radiotracer F-DCFPyL detects tumor neovasculature in metastatic, advanced, radioiodine-refractory, differentiated thyroid cancer.

Prostate-specific membrane antigen (PSMA; also termed glutamate carboxypeptidase II (GCP II)) is abundantly expressed in prostate cancer. It has been shown recently that PSMA is expressed in neovasculature of differentiated thyroid cancer. In this study, we show that F-DCFPyl might detect neovasculature in advanced, metastatic differentiated thyroid cancer (DTC).

Misdiagnosis of Paraganglioma by I-mIBG Without Stable Iodine Blockade of Thyroidal Radioiodine Uptake.

Iodine-123/iodine-131 (I/I)-metaiodobenzylguanidine (mIBG) scan is an established tool for the localization and treatment of neuroendocrine tumors such as paragangliomas (PGL). To minimize thyroid irradiation by the radioactive iodine in the mIBG preparation, blockade of thyroidal iodine uptake with high doses of stable iodine used to be given routinely as part of all mIBG protocols. As I is now more frequently utilized than I, concern about thyroid radiation has lessened and thyroid blockade is often considered unnecessary.

Thyroid and Cardiovascular Disease: Research Agenda for Enhancing Knowledge, Prevention, and Treatment.

Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, The National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease.

Thyroid and Cardiovascular Disease: Research Agenda for Enhancing Knowledge, Prevention, and Treatment.

Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, the National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease.

Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer.

The Afirma Genomic Sequencing Classifier (GSC) is a rule‐out test for malignancy/noninvasive follicular thyroid neoplasms with papillary‐like nuclear features among patients with Bethesda category III/IV nodules, whereas the complimentary Xpression Atlas provides genomic insights from a curated panel of 511 genes among GSC suspicious and Bethesda category V/VI nodules. Together, they facilitate personalized treatment decisions based on genomic insights derived from the transcriptome of the biopsied target and extend the diagnostic and therapeutic reach of cytopathologists and fine‐needle aspiration biopsy sample collection.

Surveillance for Differentiated Thyroid Cancer Recurrence.

Serum thyroglobulin monitoring along with anatomic and functional imaging play key roles in the surveillance of patients with differentiated thyroid cancer after initial treatment. Among patients with a disease stage justifying thyroid remnant ablation or with suspected metastatic disease, radioiodine whole-body scans are essential in the months after surgery. For patients with low to moderate-risk cancers, ultrasonography of the neck (with measurement of serum thyroglobulin on thyroid hormone replacement) are the best initial diagnostic modalities, and are often the only tests required.

Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy.

Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life-threatening hypercalcemia. We queried whether comprehensive genomic profiling (CGP) of PC might identify genomic alterations (GAs), which would suggest benefit from rationally matched therapeutics.

Methods: We performed hybrid-capture-based CGP to identify GAs and tumor mutational burden (TMB) in tumors from patients with this malignancy.

Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules.

Importance: Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.

Objective: To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.

Design, Setting, And Participants: A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States.

THE RELATIONSHIP OF BRAF MUTATION STATUS TO FDG PET/CT AVIDITY IN THYROID CANCER: A REVIEW AND META-ANALYSIS.

Objective: Papillary thyroid cancer (PTC) harboring a BRAF gene mutation has been shown to exhibit aggressive tumor behavior and carries higher risks of recurrence and disease-specific death. In this systematic review and meta-analysis, we examined published evidence related to the accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detection of residual disease in patients with BRAF mutated thyroid cancer.

Methods: We extracted data from PUBMED/MEDLINE and EMBASE published between January 1995 and March 2017.

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality.

Background: Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time.

Utility of I-124 PET/CT in identifying radioiodine avid lesions in differentiated thyroid cancer: a systematic review and meta-analysis.

Introduction: Diagnostic I-123 scans have been shown to underestimate the disease burden in differentiated thyroid cancer (DTC) when compared to I-131 post-treatment scans, especially in children and patients who have had prior radioiodine (RAI) therapy and/or distant metastasis. I-124 PET/CT has been shown to be highly effective in imaging DTC-related metastatic disease.

Methods: We performed a systematic review and meta-analysis of studies investigating the sensitivity and specificity of I-124 PET/CT in identifying lesions amenable to RAI therapy as confirmed by I-131 post-treatment scanning.

Mortality Risk Stratification by Combining BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Cancer: Genetic Duet of BRAF and TERT Promoter Mutations in Thyroid Cancer Mortality.

Importance: BRAF V600E and TERT promoter mutations can coexist in papillary thyroid cancer (PTC). This genetic duet was indicated to be involved in the aggressiveness of PTC, but its prognostic value in PTC-related mortality remains to be specifically established.

Objective: To establish the prognostic power of this genetic duet in PTC-specific mortality.

The true cost of thyroid surgery determined by a micro-costing approach.

Whether the amount of the current DRG tariff for thyroid surgery covers its actual cost has been questioned. We estimated a reliable cost of thyroid surgery for a large Italian hospital. A micro-costing approach is used with data from the University Hospital "Umberto I," a large facility that conducts a high volume of thyroidectomy surgical procedures in the Lazio region.

Precision Medicine Comes to Thyroidology.

The broad spectrum of thyroid disease severity--from subclinical hypothyroidism to myxedema coma, subclinical thyrotoxicosis to thyroid storm, and microscopic papillary to anaplastic cancers--has always demanded that clinicians individualize their management of thyroid patients. Deepening knowledge of thyroid pathophysiology along with advances in diagnostic, prognostic, and therapeutic technologies applicable to thyroid diseases position this field to ride the wave of precision medicine in the decade ahead.

Barriers to optimal diabetes care in Trinidad and Tobago: a health care Professionals' perspective.

Background: The republic of Trinidad and Tobago (T&T) is a middle income country with a comparatively high prevalence of diabetes mellitus (DM) compared to others in the Caribbean. To date, there have been no studies on health care professionals' (HCP) perspectives regarding the barriers to achieving optimal care of patients with DM in this country and few previous studies in the Caribbean, yet such perspectives are imperative to develop strategies that reduce the global burden of this disease.

Methods: An electronic invitation was sent to prospective HCP in T&T inviting them to attend a symposium on DM and cardiovascular disease.

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned.

Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer.

Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging.

Background: Both endogenous and exogenous thyrotoxicosis has been associated with atrial fibrillation and low bone mineral density. Therefore, this study investigated the risk factors associated with prevalent and incident thyrotoxicosis and the initiation of thyroid hormone therapy in a healthy, aging cohort.

Methods: A total of 1450 ambulatory community volunteer participants in the Baltimore Longitudinal Study of Aging examined at the NIA Clinical Research Unit in Baltimore, MD, have undergone longitudinal monitoring of serum thyrotropin (TSH) and thyroid hormone (free thyroxine and free triiodothryonine) levels as well as medication use every one to four years, depending on age, between 2003 and 2014.

Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987-2012.

Context: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer.

Objective: The objective was to examine effects of initial therapies on outcomes.