General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement.

Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules. Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided. Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine-needle aspiration.

BACKGROUND: There is limited data comparing the performance of Afirma Genomic Sequencing Classifier (GSC) in thyroid nodules carrying an initial versus a repeat diagnosis of atypia of undetermined significance (AUS). This study reported an institutional experience in this regard. MATERIALS AND METHODS: This retrospective study included consecutive thyroid nodules that had an initial or a repeat AUS diagnosis and had a subsequent GSC diagnostic result (benign or suspicious) from 2017 to 2021. All nodules were followed by surgical intervention or by clinical and/or ultrasound monitoring. GSC's benign call rate (BCR), rate of histology-proven malignancy associated with a suspicious GSC result, and diagnostic parameters of GSC were calculated and compared between the two cohorts (initial versus repeat AUS). Statistical significance was defined with a p-value of <.05 for all analysis. RESULTS: A total of 202 cases fulfilled inclusion criteria, including 67 and 135 thyroid nodules with an initial and a repeat AUS diagnosis, respectively. BCR was 67% and 66% in initial and repeat AUS cohorts, respectively. Rate of histology-proven malignancy associated with a suspicious GSC result were 22% and 24% in initial and repeat AUS cohorts, respectively. Compared with the repeat AUS cohort, the initial AUS cohort showed slightly lower sensitivity (83% vs. 100%), specificity (70% vs. 73%), PPV (23% vs. 24%), NPV (98% vs. 100%), and diagnostic accuracy (72% vs. 75%). Nevertheless, these differences did not reach statistical significance. CONCLUSION: GSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.

Physician-Reported Barriers to Osteoporosis Screening: A Nationwide Survey.

OBJECTIVE: Despite increased awareness, osteoporosis screening rates remain low. The objective of this survey study was to identify physician-reported barriers to osteoporosis screening. METHODS: We conducted a survey of 600 physician members of the Endocrine Society, American Academy of Family Practice, and American Geriatrics Society. The respondents were asked to rate barriers to osteoporosis screening in their patients. We performed multivariable logistic regression analyses to determine correlates with the most commonly reported barriers. RESULTS: Of 566 response-eligible physicians, 359 completed the survey (response rate, 63%). The most commonly reported barriers to osteoporosis screening included patient nonadherence (63%), physician concern about cost (56%), clinic visit time constraints (51%), low on the priority list (45%), and patient concern about cost (43%). Patient nonadherence as a barrier was correlated with physicians in academic tertiary centers (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.06-5.13), whereas clinic visit time constraints were correlated with physicians in both community-based academic affiliates and academic tertiary care ([OR, 1.96; 95% CI, 1.10-3.50] and [OR, 2.48; 95% CI, 1.22-5.07], respectively). Geriatricians (OR, 0.40; 95% CI, 0.21-0.76) and physicians with >10 years in practice were less likely to report clinic visit time constraints as a barrier (11-20 years: OR, 0.41; 95% CI, 0.20-0.85; >20 years: OR, 0.32; 95% CI, 0.16-0.65). Physicians with more patient-facing time (3-5 compared with 0.5-2 d/wk) were more likely to place screening low on the priority list (OR, 2.66; 95% CI, 1.34-5.29). CONCLUSION: Understanding barriers to osteoporosis screening is vital in developing strategies to improve osteoporosis care.

Management of Advanced Thyroid Cancer: Overview, Advances, and Opportunities.

Thyroid cancer is the most common endocrine malignancy with almost one million people living with thyroid cancer in the United States. Although early-stage well-differentiated thyroid cancers account for the majority of thyroid cancers on diagnosis and have excellent survival rates, the incidence of advanced-stage disease has increased over the past few years and confers poorer prognosis. Until recently, patients with advanced thyroid cancer had limited therapeutic options. However, the landscape of thyroid cancer treatment has dramatically changed in the past decade with the current availability of several novel effective therapeutic options, leading to significant advances and improved patient outcomes in the management of advanced disease. In this review, we summarize the current status of advanced thyroid cancer treatment options and discuss recent advances made in targeted therapies that have proven promising to clinically benefit patients with advanced thyroid cancer.

Current Controversies in Low-Risk Differentiated Thyroid Cancer: Reducing Overtreatment in an Era of Overdiagnosis.

CONTEXT: Low-risk differentiated thyroid cancer (DTC) is overdiagnosed, but true incidence has increased as well. Owing to its excellent prognosis with low morbidity and mortality, balancing treatment risks with risks of disease progression can be challenging, leading to several areas of controversy. EVIDENCE ACQUISITION: This mini-review is an overview of controversies and difficult decisions around the management of all stages of low-risk DTC, from diagnosis through treatment and follow-up. In particular, overdiagnosis, active surveillance vs surgery, extent of surgery, radioactive iodine (RAI) treatment, thyrotropin suppression, and postoperative surveillance are discussed. EVIDENCE SYNTHESIS: Recommendations regarding the diagnosis of DTC, the extent of treatment for low-risk DTC patients, and the intensity of posttreatment follow-up have all changed substantially in the past decade. While overdiagnosis remains a problem, there has been a true increase in incidence as well. Treatment options range from active surveillance of small tumors to total thyroidectomy followed by RAI in select cases. Recommendations for long-term surveillance frequency and duration are similarly broad. CONCLUSION: Clinicians and patients must approach each case in a personalized and nuanced fashion to select the appropriate extent of treatment on an individual basis. In areas of evidential equipoise, data regarding patient-centered outcomes may help guide decision-making.

Evaluating health outcomes in the treatment of hypothyroidism.

Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.

Towards De-Implementation of low-value thyroid care in older adults.

PURPOSE OF REVIEW: This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer. RECENT FINDINGS: Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults. SUMMARY: Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.

Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans.

Importance: Cardiovascular disease is the leading cause of death in the United States. Synthetic thyroid hormones are among the 3 most commonly prescribed medications, yet studies evaluating the association between the intensity of thyroid hormone treatment and cardiovascular mortality are scarce. Objective: To evaluate the association between thyroid hormone treatment intensity and cardiovascular mortality. Design, Setting, and Participants: This retrospective cohort study used data on 705 307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004, and December 31, 2017, with a median follow-up of 4 years (IQR, 2-9 years). Two cohorts were studied: 701 929 adults aged 18 years or older who initiated thyroid hormone treatment with at least 2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373 981 patients with at least 2 free thyroxine (FT4) measurements. Data were merged with the National Death Index for mortality ascertainment and cause of death, and analysis was conducted from March 25 to September 2, 2020. Exposures: Time-varying serum thyrotropin and FT4 levels (euthyroidism: thyrotropin level, 0.5-5.5 mIU/L; FT4 level, 0.7-1.9 ng/dL; exogenous hyperthyroidism: thyrotropin level, <0.5 mIU/L; FT4 level, >1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT4 level, <0.7 ng/dL). Main Outcomes and Measures: Cardiovascular mortality (ie, death from cardiovascular causes, including myocardial infarction, heart failure, or stroke). Survival analyses were performed using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates. Results: Of the 705 307 patients in the study, 625 444 (88.7%) were men, and the median age was 67 years (IQR, 57-78 years; range, 18-110 years). Overall, 75 963 patients (10.8%) died of cardiovascular causes. After adjusting for age, sex, traditional cardiovascular risk factors (eg, hypertension, smoking, and previous cardiovascular disease or arrhythmia), patients with exogenous hyperthyroidism (eg, thyrotropin levels, <0.1 mIU/L: adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32-1.47; FT4 levels, >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (eg, thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55-2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50-1.63) had increased risk of cardiovascular mortality compared with individuals with euthyroidism. Conclusions and Relevance: This study suggests that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions.

OBJECTIVE: The objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes. METHODS: A literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review. RESULTS: Minimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer. CONCLUSION: Surgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.

Concurrent Use of Thyroid Hormone Therapy and Interfering Medications in Older US Veterans.

CONTEXT: Thyroid hormone management in older adults is complicated by comorbidities and polypharmacy. OBJECTIVE: Determine the prevalence of concurrent use of thyroid hormone and medications that can interfere with thyroid hormone metabolism (amiodarone, prednisone, prednisolone, carbamazepine, phenytoin, phenobarbital, tamoxifen), and patient characteristics associated with this practice. DESIGN: Retrospective cohort study between 2004 and 2017 (median follow-up, 56 months). SETTING: Veterans Health Administration Corporate Data Warehouse. PARTICIPANTS: A total of 538 137 adults ≥ 65 years prescribed thyroid hormone therapy during the study period. MAIN OUTCOME MEASURE: Concurrent use of thyroid hormone and medications interfering with thyroid hormone metabolism. RESULTS: Overall, 168 878 (31.4%) patients were on at least 1 interfering medication while on thyroid hormone during the study period. In multivariable analyses, Black/African-American race (odds ratio [OR], 1.25; 95% CI, 1.21-1.28, compared with White), Hispanic ethnicity (OR, 1.12; 95% CI, 1.09-1.15, compared with non-Hispanic), female (OR, 1.11; 95% CI, 1.08-1.15, compared with male), and presence of comorbidities (eg, Charlson/Deyo Comorbidity Score ≥ 2; OR, 2.50; 95% CI, 2.45-2.54, compared with 0) were more likely to be associated with concurrent use of thyroid hormone and interfering medications. Older age (eg, ≥ 85 years; OR, 0.48; 95% CI, 0.47-0.48, compared with age 65-74 years) was less likely to be associated with this practice. CONCLUSIONS AND RELEVANCE: Almost one-third of older adults on thyroid hormone were on medications known to interfere with thyroid hormone metabolism. Our findings highlight the complexity of thyroid hormone management in older adults, especially in women and minorities.

Understanding Worry About Risks Associated With Thyroid Hormone Therapy: A National Survey of Endocrinologists, Family Physicians, and Geriatricians.

OBJECTIVE: Thyroid hormone use is widespread, and prior studies have shown that over- and undertreatment with thyroid hormone are common. Our objective was to understand physician worry regarding risks associated with thyroid hormone therapy, specifically overtreatment or undertreatment. METHODS: A nationwide survey was administered to physician members of the Endocrine Society, the American Academy of Family Practice, and the American Geriatrics Society. Participants were asked how often they were worried about various risks that may be associated with thyroid hormone over- or undertreatment, that is, cardiovascular complications, bone complications, and poor quality of life due to overtreatment or undertreatment with thyroid hormone. Multivariable regression analyses were conducted to determine physician characteristics associated with each worry. RESULTS: The response rate was 63% (359 of 566); of those who responded, 128 (36%) were primary care physicians, 114 (32%) were endocrinologists, and 113 (32%) were geriatricians. Overall, 74 (21%) physicians reported that they frequently or always worried about cardiovascular complications, 74 (21%) about bone complications, 111 (31%) about the poor quality of life due to symptoms from undertreatment with thyroid hormone, and 87 (24%) about the poor quality of life due to symptoms from overtreatment with thyroid hormone. Endocrinologists were more likely to frequently or always worry about the patients' poor quality of life due to symptoms from overtreatment (odds ratio, 2.05; 95% confidence interval, 1.09-3.93) compared with primary care physicians. CONCLUSION: Up to one third of the physicians frequently or always worried about risks resulting from the thyroid hormone overtreatment or undertreatment. More research is needed across specialties to understand physician perceptions of how thyroid hormone therapy impacts the patients' quality of life.

Nonsurgical Management of Thyroid Nodules: The Role of Ablative Therapies.

CONTEXT: After a thorough evaluation most thyroid nodules are deemed of no clinical consequence and can be observed. However, when they are compressive, toxic, or involved by papillary thyroid carcinoma surgery or radioactive iodine (RAI) (if toxic) are the treatments of choice. Both interventions can lead to hypothyroidism and other adverse outcomes (eg, scar, dysphonia, logistical limitation with RAI). Active surveillance might be used for papillary thyroid microcarcinoma (PTMC) initially, but anxiety leads many cases to surgery later. Several ablative therapies have thus evolved over the last few years aimed at treating these nodules while avoiding described risks. CASES: We present 4 cases of thyroid lesions causing concern (compressive symptoms, thyrotoxicosis, anxiety with active surveillance of PTMC). The common denominator is patients' attempt to preserve thyroid function, bringing into focus percutaneous ethanol injection (PEI) and thermal ablation techniques (radiofrequency ablation [RFA] being the most common). We discuss the evidence supporting these approaches and compare them with standard therapy, where evidence exists. We discuss additional considerations for the utilization of these therapies, their side-effects, and conclude with a simplified description of how these procedures are performed. CONCLUSION: Thermal ablation, particularly RFA, is becoming an attractive option for managing a subgroup of solid thyroid nodules, while PEI has a role in managing thyroid cysts and a select group of PTMC. Their role in the algorithm of thyroid nodule management is still being refined and technical expertise will be essential to reproduce the reported results into everyday practice.