Thyroid Function and Cognitive Decline: A Narrative Review.

OBJECTIVE: As the population of older adults in the United States continues to rise, understanding modifiable risk factors that contribute to cognitive decline and dementia becomes increasingly important. This narrative review summarizes existing literature on the association between thyroid function in the euthyroid range, hypothyroidism and hyperthyroidism, and cognitive outcomes in older adults. METHODS: A comprehensive literature search of the PubMed and Ovid/Medline databases was conducted. Randomized controlled trials, systematic reviews, meta-analyses, and observational studies published in English between January 2000 and December 2023 were included. RESULTS: Overall, existing studies yielded conflicting results, failing to delineate a concrete relationship between thyroid function and cognitive outcomes and/or dementia in older adults. There may be a possible association between higher thyroid stimulating hormone in the reference range and lower risk of incident dementia, which may be more pronounced in women. Majority of studies elucidated a possible association between low thyroid stimulating hormone and incident dementia, with suggestion that duration of hyperthyroidism may contribute to increasing dementia risk. Even though evidence on the association of hypothyroidism and cognitive decline are disparate, current data do not support treatment of subclinical hypothyroidism to improve cognitive outcomes in older adults. CONCLUSION: Despite numerous studies, there is no conclusive evidence that supports a direct relationship between hyperthyroidism or hypothyroidism and cognitive decline. Study limitations include heterogeneity in study designs, measurement methodologies, and cognitive assessment tools. Future research is needed to better delineate whether an association exists and whether treatment of thyroid dysfunction ameliorates cognitive impairment.

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.

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.

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.

Thyroid Nodule Evaluation and Management in Older Adults: A Review of Practical Considerations for Clinical Endocrinologists.

OBJECTIVE: Contextualizing the evaluation of older adults with thyroid nodules is necessary to fully understand which management strategy is the most appropriate. Our goal was to summarize available clinical evidence to provide guidance in the care of older adults with thyroid nodules and highlight special considerations for thyroid nodule evaluation and management in this population. METHODS: We conducted a literature search of PubMed and Ovid MEDLINE from January 2000 to November 2020 to identify relevant peer-reviewed articles published in English. References from the included articles as well as articles identified by the authors were also reviewed. RESULTS: The prevalence of thyroid nodules increases with age. Although thyroid nodules in older adults have a lower risk of malignancy, identified cancers are more likely to be of high-risk histology. The goals of thyroid nodule evaluation and the tools used for diagnosis are similar for older and younger patients with thyroid nodules. However, limited evidence exists regarding thyroid nodule evaluation and management to guide personalized decision making in the geriatric population. CONCLUSION: Considering patient context is significant in the diagnosis and management of thyroid nodules in older adults. When making management decisions in this population, it is essential to carefully weigh the risks and benefits of thyroid nodule diagnosis and treatment, in view of older adults' higher prevalence of high-risk thyroid cancer as well as increased risk for multimorbidity, functional and cognitive decline, and treatment complications.

Disparities in risk perception of thyroid cancer recurrence and death.

BACKGROUND: To the authors' knowledge, studies regarding risk perception among survivors of thyroid cancer are scarce. METHODS: The authors surveyed patients who were diagnosed with differentiated thyroid cancer from the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County (2632 patients; 63% response rate). The analytic cohort was defined by a ≤5% risk of disease recurrence and mortality (1597 patients). Patients estimated their recurrence and mortality risks separately (increments of 10% and endpoints of ≤5% and ≥95%). Both outcomes were dichotomized between reasonably accurate estimates (risk perception of ≤5% or 10%) versus overestimation (risk perception of ≥20%). Multivariable logistic regression was used to identify factors associated with risk overestimation, and the relationships between overestimation and both worry and quality of life were evaluated. RESULTS: In the current study sample, 24.7% of patients overestimated their recurrence risk and 12.5% overestimated their mortality risk. A lower educational level was associated with overestimating disease recurrence (≤high school diploma: odds ratio [OR], 1.64 [95% CI, 1.16-2.31]; and some college: OR, 1.36 [95% CI, 1.02-1.81]) and mortality (≤high school diploma: OR, 1.86 [95% CI, 1.18-2.93]) risk compared with those attaining at least a college degree. Hispanic ethnicity was found to be associated with overestimating recurrence risk (OR, 1.44, 95% CI 1.02-2.03) compared with their white counterparts. Worry about recurrence and death was found to be greater among patients who overestimated versus those who had a reasonably accurate estimate of their risk of disease recurrence and mortality, respectively (P < .001). Patients who overestimated mortality risk also reported a decreased physical quality of life (mean T score, 43.1; 95% CI, 41.6-44.7) compared with the general population. CONCLUSIONS: Less educated patients and Hispanic patients were more likely to report inaccurate risk perceptions, which were associated with worry and a decreased quality of life.

Understanding Osteoporosis Screening Practices in Men: A Nationwide Physician Survey.

OBJECTIVE: To understand osteoporosis screening practices, particularly in men, by a diverse cohort of physicians, including primary care physicians, endocrinologists, and geriatricians. METHODS: We surveyed randomly selected members of the American Academy of Family Practice, Endocrine Society, and American Geriatrics Society. Respondents were asked to rate how often they would screen for osteoporosis in four different clinical scenarios by ordering a bone density scan. Multivariable logistic regression analyses were conducted to determine factors associated with offering osteoporosis screening in men in each clinical scenario. Physicians were also asked to note factors that would lead to osteoporosis screening in men. RESULTS: Response rate was 63% (359/566). While 90% respondents reported that they would always or frequently screen for osteoporosis in a 65-year-old post-menopausal woman, only 22% reported they would screen a 74-year-old man with no significant past medical history. Endocrinologists were more likely to screen a 74-year-old man compared to primary care physicians (odds ratio, 2.32; 95% confidence interval, 1.10 to 4.88). In addition to chronic steroid use (94%), history of nontraumatic fractures (88%), and androgen-deprivation therapy for prostate cancer (82%), more than half the physicians reported suppressive doses of thyroid hormone (64%) and history of falls (52%) as factors leading to screening for osteoporosis in men. CONCLUSIONS: Our survey results highlight heterogeneity in osteoporosis screening in men, with underscreening in some scenarios compared to women, and identify factors that lead to screening in men. These findings can help design interventions to improve osteoporosis screening in men.

Risk of Osteoporosis and Fractures in Patients with Thyroid Cancer: A Case-Control Study in U.S. Veterans.

BACKGROUND: Data on osteoporosis and fractures in patients with thyroid cancer, especially men, are conflicting. Our objective was to determine osteoporosis and fracture risk in U.S. veterans with thyroid cancer. MATERIALS AND METHODS: This is a case-control study using the Veterans Health Administration Corporate Data Warehouse (2004-2013). Patients with thyroid cancer (n = 10,370) and controls (n = 10,370) were matched by age, sex, weight, and steroid use. Generalized linear mixed-effects regression model was used to compare the two groups in terms of osteoporosis and fracture risk. Next, subgroup analysis of the patients with thyroid cancer using longitudinal thyroid-stimulating hormone (TSH) was performed to determine its effect on risk of osteoporosis and fractures. Other covariates included patient age, sex, median household income, comorbidities, and steroid and androgen use. RESULTS: Compared with controls, osteoporosis, but not fractures, was more frequent in patients with thyroid cancer (7.3% vs. 5.3%; odds ratio [OR], 1.33; 95% confidence interval [CI], 1.18-1.49) when controlling for median household income, Charlson/Deyo comorbidity score, and androgen use. Subgroup analysis of patients with thyroid cancer demonstrated that lower TSH (OR, 0.93; 95% CI, 0.90-0.97), female sex (OR, 4.24; 95% CI, 3.53-5.10), older age (e.g., ≥85 years: OR, 17.18; 95% CI, 11.12-26.54 compared with <50 years), and androgen use (OR, 1.63; 95% CI, 1.18-2.23) were associated with osteoporosis. Serum TSH was not associated with fractures (OR, 1.01; 95% CI, 0.96-1.07). CONCLUSION: Osteoporosis, but not fractures, was more common in U.S. veterans with thyroid cancer than controls. Multiple factors may be contributory, with low TSH playing a small role. IMPLICATIONS FOR PRACTICE: Data on osteoporosis and fragility fractures in patients with thyroid cancer, especially in men, are limited and conflicting. Because of excellent survival rates, the number of thyroid cancer survivors is growing and more individuals may experience long-term effects from the cancer itself and its treatments, such as osteoporosis and fractures. The present study offers unique insight on the risk for osteoporosis and fractures in a largely male thyroid cancer cohort. Physicians who participate in the long-term care of patients with thyroid cancer should take into consideration a variety of factors in addition to TSH level when considering risk for osteoporosis.

REFERRAL OF OLDER THYROID CANCER PATIENTS TO A HIGH-VOLUME SURGEON: RESULTS OF A MULTIDISCIPLINARY PHYSICIAN SURVEY.

OBJECTIVE: Surgical outcomes of thyroid cancer patients are improved with high-volume surgeons. However, age disparities in referral to specialist surgical centers still exist. The factors that influence decision making regarding referral of older thyroid cancer patients to high-volume surgeons remain unknown. METHODS: We surveyed members of the Endocrine Society, American College of Physicians, and American Academy of Family Practice. RESULTS: Overall, 270 physicians completed the survey. Patient preference (69%), transportation barriers (62%), and confidence in local surgeon (54%) were the most cited factors decreasing likelihood of referral to a high-volume surgeon. In clinical scenarios, referral rates to a high-volume surgeon were similar for patients aged 40 and 65 years with a 1-cm thyroid nodule diagnostic of thyroid cancer (n = 137 [54%]; n = 132 [52%], respectively) as for an 85-year-old with a 4-cm nodule (n = 148 [59%]). When comorbidities were introduced, more physicians (n = 186 [74%]) would refer a 65-year-old with a 4-cm thyroid nodule and comorbidities, compared to an 85-year-old with the same nodule size without comorbidi-ties. In multivariable analysis, treating >10 thyroid cancer patients/year (P<.001; P<.005) and endocrinology specialty (P = .003; P = .003) were associated with referral to a high-volume surgeon for a 65-year-old with comorbidities and an 85-year-old without comorbidities, respectively. CONCLUSION: Understanding surgical referral patterns of older thyroid cancer patients is vital in identifying obstacles in the referral process. We found that patient factors including comorbidities and physician factors including specialty and patient volume influence these patterns. This is the first step towards developing targeted interventions for these patients.

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

BACKGROUND: The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. MATERIALS AND METHODS: A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. RESULTS: Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. CONCLUSION: Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. IMPLICATIONS FOR PRACTICE: The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy, and discordant results have been reported on its adverse effects on bone. The present review provides physicians with existing data on the skeletal effects of thyrotropin suppression therapy, highlighting the need for further research to identify the groups at risk of adverse skeletal effects. This knowledge will aid in developing tailored thyroid cancer treatment.

THE IMPACT OF AGE IN THE MANAGEMENT OF HYPOTHYROIDISM: RESULTS OF A NATIONWIDE SURVEY.

OBJECTIVE: Evidence exists that thyroid-stimulating hormone (TSH) increases with age and lowering the TSH goal in older patients on thyroid hormone may cause over-treatment. Risks of overtreatment include cardiac and skeletal events. We assessed practice patterns regarding TSH goals and explored factors influencing physicians' decision making when managing hypothyroidism. METHODS: Members of the American College of Physicians, the American Academy of Family Practice, and the Endocrine Society were surveyed to determine goal TSH when treating hypothyroidism. RESULTS: Fifty-three percent of physicians reported factoring patient age into their decision making when managing hypothyroidism. Patient age was prioritized third (53%), following patient symptoms (69.2%) and cardiac arrhythmias (65.7%). In multivariable analysis, endocrinologists (P = .002), internists (P = .049), physicians in academic settings (P = .003), and high-volume physicians (P = .021) were more likely to consider patient age when determining goal TSH. When presented with scenarios differing in patient gender and age, 90% of physicians targeted a TSH ≤3.0 mIU/L in 30-year-old patients. Fifty-three percent of respondents targeted a TSH ≤3.0 mIU/L in octogenarians, but 90% targeted a TSH >1.5 mIU/L in this group. Regardless of gender, physician-reported TSH goal ranges (0.1 to 0.5, 0.6 to 1.5, 1.6 to 3.0, and 3.1 to 5.0 mIU/L) increased in a direct relationship to patient age (P<.001). CONCLUSION: Just over half of physicians consider patient age when determining TSH goal. When presented with scenarios differing in patient age and gender, physicians targeted a higher TSH goal in octogenarians. This may indicate an attempt to avoid overtreatment in this group. Consensus is needed among physicians regarding the role of patient age in hypothyroidism management. ABBREVIATIONS: TSH = thyroid-stimulating hormone.

New insights in risk stratification of differentiated thyroid cancer.

PURPOSE OF REVIEW: Numerous staging and scoring systems exist for differentiated thyroid cancer (DTC), but all harbor limitations. This has prompted investigation for new factors with prognostic implications for DTC. RECENT FINDINGS: Several new factors that may be involved in DTC risk stratification have emerged, such as thyroid stimulating hormone and molecular markers. In addition, others are controversial and being challenged, such as age, sex and lymph node involvement. SUMMARY: The purpose of this review is to present recent updates in the literature on new potential risk stratification predictors for DTC.

Physician-reported barriers and facilitators to thyroid hormone deprescribing in older adults.

BACKGROUND: Thyroid hormone is one of the most commonly prescribed medications in the United States. Misuse of and overtreatment with thyroid hormone is common in older adults and can lead to cardiovascular and skeletal adverse events. Even though deprescribing can reduce inappropriate care, no studies have yet explored specific barriers and facilitators to guide thyroid hormone deprescribing in older adults (defined as discontinuation of thyroid hormone when initiated without an appropriate indication or dose reduction in those overtreated). METHODS: We conducted semi-structured interviews with 19 endocrinologists, geriatricians, and primary care physicians who prescribe thyroid hormone. Interviews were completed between July 2020 and December 2021 via two-way video conferencing. We used both an inductive and deductive content analysis guided by the Theoretical Domains Framework to evaluate transcribed and coded participant responses. Thematic analysis characterized themes related to barriers and facilitators to thyroid hormone deprescribing practices in older adults. RESULTS: The most commonly reported barriers to thyroid hormone deprescribing were related to patient-level factors, followed by physician- and system-level factors. Patient factors included patients' perceived need for thyroid hormone use and patient anxiety/concerns about potential side effects related to thyroid hormone dose reduction, patient lack of knowledge, and misinformation regarding deprescribing. Physician- and system-level barriers included clinic visit time constraints, physician inertia, physician lack of knowledge about deprescribing, perceived lack of sufficient patient follow-up, and electronic health record limitations. The most prominent physician-reported facilitators to thyroid hormone deprescribing were effective physician-to-patient communication, and positive physician-patient relationship, including patients' trust in their treating physician. CONCLUSION: Barriers and facilitators to thyroid hormone deprescribing in older adults were reported at multiple levels including patient-, physician-, and system-level factors. Interventions to improve thyroid hormone deprescribing in older adults should aim to improve patient education and expectations, increase multidisciplinary physician awareness, and overcome physician inertia.

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.

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.