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Phosphatidylcholine is a ubiquitous phospholipid. It contains a phosphocholine (PC) headgroup and polyunsaturated fatty acids that, when oxidized, form reactive oxidized phospholipids (PC-OxPLs). PC-OxPLs are pathogenic in multiple diseases and neutralized by anti-PC IgM antibodies. The levels of anti-PC IgM increase as the levels of PC-OxPLs increase and, in humans, are inversely correlated with the incidence of cardiovascular diseases and steatohepatitis. PC-OxPLs also decrease bone mass in mice. Overexpression of anti-PC IgM ameliorates atherosclerosis and steatohepatitis, increases bone mass in young mice, and protects against high fat diet- and age-associated osteoporosis. We investigated the relationship between anti-PC IgM plasma levels and bone mineral density (BMD) in a cross-sectional study of 247 participants [mean age: 65.5 (± 8.6) years] without medical conditions known to influence BMD or antibody production. Anti-PC IgM levels negatively correlated with both T- and Z-scores at the lumbar spine, femur and, to a lesser extent, the forearm. These correlations were maintained after adjustment for age, race, and sex. These results raise the possibility that higher levels of anti-PC IgM in patients with lower BMD reflect exposure to higher levels of PC-OxPLs, which are known to affect bone mass, and could be a novel risk marker for osteoporosis. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine is a ubiquitous phospholipid. It contains a phosphocholine (PC) headgroup and polyunsaturated fatty acids that, when oxidized, form reactive oxidized phospholipids (PC-OxPLs). PC-OxPLs are pathogenic in multiple diseases and neutralized by anti-PC IgM antibodies. The levels of anti-PC IgM increase as the levels of PC-OxPLs increase and, in humans, are inversely correlated with the incidence of cardiovascular diseases and steatohepatitis. PC-OxPLs also decrease bone mass in mice. Overexpression of anti-PC IgM ameliorates atherosclerosis and steatohepatitis, increases bone mass in young mice, and protects against high fat diet- and age-associated osteoporosis. We investigated the relationship between anti-PC IgM plasma levels and bone mineral density (BMD) in a cross-sectional study of 247 participants [mean age: 65.5 (± 8.6) years] without medical conditions known to influence BMD or antibody production. Anti-PC IgM levels negatively correlated with both T- and Z-scores at the lumbar spine, femur and, to a lesser extent, the forearm. These correlations were maintained after adjustment for age, race, and sex. These results raise the possibility that higher levels of anti-PC IgM in patients with lower BMD reflect exposure to higher levels of PC-OxPLs, which are known to affect bone mass, and could be a novel risk marker for osteoporosis. [ABSTRACT FROM AUTHOR]

Background/Objectives: There is evidence of overtreatment in patients with subclinical hypothyroidism (SCH). We aimed to identify the proportion of patients treated for SCH and the determinants of thyroid hormone therapy initiation. Methods: We included a random sample of adult Veterans diagnosed with SCH from 1 January 2016 to 31 December 2018 and conducted univariate and multivariable logistic regression to identify factors associated with levothyroxine initiation. Results: Out of 229 Veterans with SCH [90.0% male, 87.2% White, 99.1% non-Hispanic, median age (interquartile range; IQR) 68 (17) years], 27.5% were treated with levothyroxine. The treated group had a higher proportion of White patients (95.2% vs. 84.2%, p = 0.039), a higher thyrotropin level [median (IQR), 6.98 (2.06) mIU/L vs. 6.14 (1.10) mIU/L, p = 0.0002], a higher proportion of patients with thyrotropin level ≥ 10 mIU/L (11.1% vs. 3.0%, p = 0.021), a lower frequency of confirmatory thyroid testing before initiating levothyroxine (49.2% vs. 97.0%, p < 0.0001), and a similar frequency of thyroid autoimmunity testing (3.2% vs. 0.6%, p = 0.18) compared to the untreated group. In a multivariable logistic regression analysis, White race (OR = 4.50, 95% CI 1.19 to 17.08, p = 0.026) and index thyrotropin level [OR = 1.71, 95% CI 1.24 to 2.35, p = 0.001; for every SD increase (1.6 mIU/L)] were associated with higher odds of treatment. Conclusions: Three in 10 Veterans with SCH received levothyroxine, often based on a single abnormal thyroid test without autoimmunity assessment. White race and higher thyrotropin level were linked to increased odds of starting treatment, indicating potential disparities and the influence of SCH severity on decision-making. [ABSTRACT FROM AUTHOR]

Context: Thyroid-stimulating hormone (TSH) is one of the most ordered laboratory tests. Objective: Determine trends of TSH testing rates and components of thyroid function testing. Methods: This was a retrospective analysis of adults 18-64 years old without evidence of thyroid disease with at least 365 days of continuous enrollment between 2006 and 2020 in the IBM MarketScan Claims Database. The main outcome measures were trends of TSH tests/1000 eligible patient-months stratified by age, sex, and region and composition of thyroid function testing. Results: Among 67 353 280 patients meeting eligibility criteria, we identified 25 606 518 TSH tests and 15 138 211 patients with ≥1 TSH test. Patients contributing an episode of TSH testing were most commonly 45-54 years old (29.8%) and female (63.6%). TSH testing rates remained consistent throughout the study period with 11.4 and 11.7 TSH tests/1000 person-months in the first and last study months, respectively (mean 12.2 TSH tests/1000 person-months). TSH testing rates dropped sharply in the spring of 2020 (4.2 TSH tests/1000 person-months). Females showed a nearly 2-fold higher rate of TSH testing than males (16.1 TSH tests/1000 person-months vs 8.6 TSH tests/1000 person-months). TSH testing rates increased with age (8.2 TSH tests/1000 person-months among individuals 18-34 years old vs 15.4 TSH tests/1000 personmonths among individuals 55-64 years old). No difference in TSH testing rates was noted between regions. Thyroid function testing episodes included only TSH in most cases (70.8%). Conclusion: TSH testing rates among commercially insured individuals without known thyroid disease appears stable over time, with higher frequency in females and with increasing age. [ABSTRACT FROM AUTHOR]

Context Levothyroxine is one of the most prescribed medications in the United States. Objective This study explores the appropriateness of levothyroxine prescriptions. Methods A retrospective multicenter study was conducted on adult patients who were prescribed levothyroxine for the first time between 2017 and 2020 at three academic centers in the United States. We classified each case of levothyroxine initiation into one of three mutually exclusive categories: appropriate (clinically supported), indeterminate (clinically unclear), or nonevidence based (NEB, not clinically supported). Results A total of 977 participants were included. The mean age was 55 years (SD 19), there was female (69%) and White race predominance (84%), and 44% had possible hypothyroid symptoms. Nearly half of the levothyroxine prescriptions were considered NEB (528, 54%), followed by appropriate (307, 31%) and indeterminate (118, 12%). The most common reason for NEB prescription was an index thyrotropin (TSH) value of less than 10 mIU/L without previous TSH or thyroxine values (131/528, 25%), for appropriate prescription, was overt hypothyroidism (163/307, 53%), and for an indeterminate prescription was a nonconfirmed subclinical hypothyroidism with TSH greater than or equal to 10 mIU/L (no confirmatory testing) (51/118, 43%). In multivariable analysis, being female (odds ratio [OR]: 1.3; 95% CI, 1.0-1.7) and prescription by a primary care provider (OR: 1.5; 95% CI, 1.2-2.0) were associated with NEB prescriptions. Conclusion There is a considerable proportion of NEB levothyroxine prescriptions. These results call for additional research to replicate these findings and to explore the perspective of those prescribing and receiving levothyroxine. [ABSTRACT FROM AUTHOR]

Background: Thyroid storm is a state of circulating thyroid hormone excess leading to multiorgan dysfunction and systemic decompensation. It typically occurs in the setting of poorly controlled hyperthyroidism and a precipitating illness or event. Management of thyroid storm in pregnancy poses unique diagnostic and therapeutic challenges. Main body: Thyroid storm is a clinical diagnosis characterized by hyperpyrexia, tachyarrhythmias, congestive heart failure, gastrointestinal and neuropsychiatric disturbances. However, diagnostic scoring systems have not been validated in pregnancy. Treatment involves specialist consultation, supportive care, and pharmacological options such as anti-thyroid medications, beta blockers, iodine solutions, glucocorticoids, and cholestyramine. These must be adapted and modified in pregnancy to prevent fetal and maternal complications. Conclusion: There is a critical need to recognize thyroid storm during pregnancy and initiate proper medical interventions promptly. [ABSTRACT FROM AUTHOR]

Background: The frequency and factors associated with thyroid hormone replacement therapy among patients with subclinical hypothyroidism (SCH) remain uncertain. Methods: In this electronic health records-based observational cohort study, we included adults diagnosed with SCH from four academic centers (the United States and Mexico) from January 1, 2016, to December 31, 2018. We aimed to identify the determinants of thyroid hormone replacement therapy for SCH and the frequency of treated SCH. Results: A total of 796 patients (65.2% women) had SCH, and 165 (20.7%) were treated with thyroid hormone replacement therapy. The treated group was younger [51.0 (standard deviation {SD} 18.3) vs. 55.3 (SD 18.2) years, p = 0.008] and had a higher proportion of women (72.7% vs. 63.2%, p = 0.03) compared with the untreated group. Only 46.7% of patients in the treated group and 65.6% in the untreated group had confirmatory thyroid function tests (TFTs) before the decision to start thyroid hormone replacement therapy was made. There was no difference in the frequency of thyroid autoimmunity evaluation, but a positive thyroid autoimmunity test was more frequent in the treated group compared with the untreated group (48.2% vs. 20.3%, p < 0.001). In a multivariable logistic regression model, female sex (odds ratio [OR] = 1.71 [CI 1.13–2.59], p = 0.01) and index thyrotropin (TSH) level (OR = 1.97 [CI 1.56–2.49], p < 0.001 for every SD [2.75 mIU/L] change) were associated with higher odds of treatment. Conclusions: Among patients with SCH, female sex and index TSH level were associated with higher odds of treatment. Moreover, in our population, the decision to treat or not to treat SCH was often based on only one set of abnormal TFTs, and thyroid autoimmunity assessment was underused. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate thyroid cancer risk clinician-patient communication among patients receiving usual counseling and counseling enhanced by a conversation aid. A secondary analysis of clinical visit recordings and post-visit surveys obtained during a trial assessing the impact of a conversation aid for patients with thyroid nodules was conducted. We assessed how thyroid cancer risk was communicated, different risk communication strategies between groups, and predictors of accurate cancer risk perception. Fifty-nine patients were analyzed. Most were women (90%) and middle-aged (median 57 years). A verbal description of thyroid cancer risk was present most frequently (83%) and was more frequent in the conversation aid than the usual care group (100% vs. 63%, p < 0.001). A numerical description using percentages was present in 41% of visits and was more frequent in the conversation aid group (59% vs. 19%, p = 0.012). Natural frequencies (7%) and positive/negative framing (10%) were utilized less commonly. Uncertainty about risks was not discussed. No predictors of accurate risk perception were identified. Clinicians most commonly present a verbal description of thyroid cancer risk. Less commonly, natural frequencies, negative/positive framing, or uncertainty is discussed. Clinicians caring for patients with thyroid nodules should be aware of different strategies for communicating thyroid cancer risk. [ABSTRACT FROM AUTHOR]

Objective: This work aims to guide clinicians practicing endocrinology in the use of telehealth (synchronous patient-clinician visits conducted over video or telephone) for outpatient care. Participants: The Endocrine Society convened a 9-member panel of US endocrinologists with expertise in telehealth clinical care, telehealth operations, patient-centered care, health care delivery research, and/or evidence-based medicine. Evidence: The panel conducted a literature search to identify studies published since 2000 about telehealth in endocrinology. One member extracted a list of factors affecting the quality of endocrine care via telehealth from the extant literature. The panel grouped these factors into 5 domains: clinical, patient, patient-clinician relationship, clinician, and health care setting and technology. Consensus Process: For each domain, 2 or 3 members drew on existing literature and their expert opinions to draft a section examining the effect of the domain's component factors on the appropriateness of telehealth use within endocrine practice. Appropriateness was evaluated in the context of the 6 Institute of Medicine aims for health care quality: patient-centeredness, equity, safety, effectiveness, timeliness, and efficiency. The panel held monthly virtual meetings to discuss and revise each domain. Two members wrote the remaining sections and integrated them with the domains to create the full policy perspective, which was reviewed and revised by all members. Conclusions: Telehealth has become a common care modality within endocrinology. This policy perspective summarizes the factors determining telehealth appropriateness in various patient care scenarios. Strategies to increase the quality of telehealth care are offered. More research is needed to develop a robust evidence base for future guideline development. [ABSTRACT FROM AUTHOR]

Context: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria. [ABSTRACT FROM AUTHOR]

Purpose: Assess the effect of intensive vs conventional blood pressure goals on patient-important outcomes in older adults with type 2 diabetes. Methods: A comprehensive search was performed using electronic databases. Randomized controlled trials comparing intensive vs conventional blood pressure goals in adults over 60 years of age with type 2 diabetes were included. Events were evaluated using a modified Mantel-Haenszel meta-analysis with Peto's method. Study selection and data extraction were performed independently and in duplicate. Results: Seven trials were included. A 19% risk reduction (OR 0.81; 95% CI 0.69–0.95; I2 = 8%; p = 0.35) in the occurrence of major adverse cardiovascular events (MACE) and 37% risk reduction (OR 0.63; 95% CI 0.51–0.79; I2 = 0%; p = 0.56) in the occurrence of fatal or non-fatal stroke was documented in the intensive treatment group. There were no differences in the occurrence of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease. Data regarding treatment adverse effects and microvascular outcomes was scarce. Conclusions: Intensive blood pressure goals in older patients with diabetes were associated with a lower risk of stroke and MACE, but not with all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and peripheral vascular disease. Highlights: This is the first review on the effect of intensive blood pressure goals in older patients who have diabetes. This analysis provides evidence that intensive blood pressure goals in older patients with diabetes are associated with a lower risk of stroke and MACE. There were no differences in all-cause mortality, CV mortality, non-fatal myocardial infarction, and peripheral vascular disease. The pros and cons of an intensive approach should be discussed with patients given that it could increase the number of medications, cost, and adverse events. Clinicians should address these results with caution, as the estimates are not robust enough to recommend a specific blood pressure goal due to the heterogeneity of goals and interventions among the included studies. [ABSTRACT FROM AUTHOR]

Context: Thyroid nodule risk stratification allows clinicians to standardize the evaluation of thyroid cancer risk according to ultrasound features. Objective: To evaluate interrater agreement among clinicians assessing thyroid nodules ultrasound features and thyroid cancer risk categories. Design, setting, and participants: We surveyed Endocrine Society and Latin American Thyroid Society members to assess their interpretation of composition, echogenicity, shape, margins, and presence of echogenic foci of 10 thyroid nodule cases. The risk category for thyroid cancer was calculated following the American College of Radiology-Thyroid Imaging Reporting & Data System (ACR-TIRADS) framework from individual responses. Main Outcomes and Measures: We used descriptive statistics and Gwet’s agreement coefficient (AC1) to assess the primary outcome of interrater agreement for ACR-TIRADS risk category. As secondary outcomes, the interrater agreement for individual features and a subgroup analysis of interrater agreement for the ACR-TIRADS category were performed (ultrasound reporting system, type of practice, and number of monthly appraisals). Results: A total of 144 participants were included, mostly endocrinologists. There was moderate level of agreement for the absence of echogenic foci (AC1 0.53, 95% CI 0.24-0.81) and composition (AC1 0.54, 95% CI 0.36-0.71). The agreement for margins (AC1 0.24, 95% CI 0.15-0.33), echogenicity (AC1 0.34, 95% CI 0.22-0.46), and shape assessment (AC1 0.42, 95% CI 0.13-0.70) was lower. The overall agreement for ACR-TIRADS assessment was AC1 0.29, (95% CI 0.13-0.45). The AC1 of ACR-TIRADS among subgroups was similar. Conclusions: This study found high variation of judgments about ACR-TIRADS risk category and individual features, which poses a potential challenge for the widescale implementation of thyroid nodule risk stratification. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative–positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose–response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes. [ABSTRACT FROM AUTHOR]

Objective: To support patient‐centred care and the collaboration of patients and clinicians, we developed and pilot tested a conversation aid for patients with thyroid nodules. Design, Patient and Measurements: We developed a web‐based Thyroid NOdule Conversation aid (TNOC) following a human‐centred design. A proof of concept observational pre–post study was conducted (TNOC vs. usual care [UC]) to assess the impact of TNOC on the quality of conversations. Data sources included recordings of clinical visits, post‐encounter surveys and review of electronic health records. Summary statistics and group comparisons are reported. Results: Sixty‐five patients were analysed (32 in the UC and 33 in the TNOC cohort). Most patients were women (89%) with a median age of 57 years and were incidentally found to have a thyroid nodule (62%). Most thyroid nodules were at low risk for thyroid cancer (71%) and the median size was 1.4 cm. At baseline, the groups were similar except for higher numeracy in the TNOC cohort. The use of TNOC was associated with increased involvement of patients in the decision‐making process, clinician satisfaction and discussion of relevant topics for decision making. In addition, decreased decisional conflict and fewer thyroid biopsies as the next management step were noted in the TNOC cohort. No differences in terms of knowledge transfer, length of consultation, thyroid cancer risk perception or concern for thyroid cancer diagnosis were found. Conclusion: In this pilot observational study, using TNOC in clinical practice was feasible and seemed to help the collaboration of patients and clinicians. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria. Methods: We conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis. Results: Of the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group. Conclusion: LT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension. [ABSTRACT FROM AUTHOR]

Purpose: Nearly half the cases of thyroid cancer, a malignancy rapidly rising in incidence within the United States, are attributable to small and asymptomatic papillary thyroid cancers that will not increase mortality. A primary driver of thyroid cancer overdiagnosis is ultrasound use. It is therefore valuable to understand how inappropriate use of thyroid ultrasound is defined, analyze the current evidence for its frequency, and identify interventions to lessen misuse. Methods: Ovid MEDLINE(R), Ovid EMBASE, and Scopus databases were searched from inception to June 2020 for studies assessing inappropriate use of thyroid ultrasound. Reviewers, working independently and in duplicate, evaluated studies for inclusion, extracted data, and graded risk of bias. We used a random-effects model with a generalized linear mixed approach to calculate the mean overall proportion estimates of inappropriate use. Results: Seven studies (total n = 1573) met the inclusion criteria with moderate to high risk of bias. Inappropriate thyroid ultrasound use was described variably, using published practice guidelines, third-party expert reviewers, or author interpretations of the literature. The overall frequency of inappropriate thyroid ultrasound use was 46% (95% CI 15–82%; n = 388) and 34% (95% CI 16–57%; n = 190) among studies using guideline based definitions. The pooled frequency of iUS due to thyroid dysfunction (either hypothyroidism or thyrotoxicosis) was 17% (95% CI 7–37%; n = 191) and the frequency of iUS due to nonspecific symptoms without a palpable mass was 11% (95% CI 5–22%; n = 124). No study examined interventions to address inappropriate use. Conclusions: Low quality evidence suggests that inappropriate use of thyroid ultrasound is common. Interventional studies aiming to decrease the inappropriate use of thyroid ultrasound are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Combined therapy with levothyroxine (LT4)/L-triiodothyronine (LT3) has garnered attention among clinicians and patients as a potential treatment alternative to LT4 monotherapy. The objective of this study was to compare the benefits and harms of LT4/LT3 combined therapy and LT4 monotherapy for patients with hypothyroidism. Methods: A systematic search in MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials was performed by a librarian from inception date until September 2020. Randomized clinical trials and quasiexperimental studies comparing combined therapy (LT4/LT3) versus monotherapy (LT4) for adult patients with hypothyroidism were considered for inclusion. Independent data extraction was performed by paired reviewers. A meta-analysis comparing standardized mean differences of the effect of each therapy was performed on clinical outcomes and patient preferences. Proportions of adverse events and reactions were assessed narratively. Results: A total of 1398 references were retrieved, from which 18 fulfilled the inclusion criteria. Results supported by evidence at low-to-moderate certainty evidence did not display a difference in treatment effect between therapies on clinical status, quality of life, psychological distress, depressive symptoms, and fatigue; all measured with standardized questionnaires. Furthermore, meta-analysis of patient preferences revealed higher proportions of choice for combined therapy (43%) when compared with monotherapy (23%) or having no preference (30%). When evaluating treatment adverse events or adverse reactions, similar proportions were observed between treatment groups; meta-analysis was not possible. Conclusions: The available evidence at low-to-moderate certainty demonstrates that there is no difference in clinical outcomes between LT4/LT3 combined therapy and LT4 monotherapy for treating hypothyroidism in adults, except for a higher proportion of patient preferring combined therapy. Adverse events and reactions appear to be similar across both groups, however, this observation is only narrative. These results could inform shared decision-making conversations between patients with hypothyroidism and their clinicians. PROSPERO Registration ID: CRD42020202658. [ABSTRACT FROM AUTHOR]

Low-value care exposes patients to ineffective, costly, and potentially harmful care. In endocrinology, low-value care practices are common in the care of patients with highly prevalent conditions. There is an urgent need to move past the identification of these practices to an active process of de-implementation. However, clinicians, researchers, and other stakeholders might lack familiarity with the frameworks and processes that can help guide successful de-implementation. To address this gap and support the de-implementation of low-value care, we provide a summary of low-value care practices in endocrinology and a primer on the fundamentals of de-implementation science. Our goal is to increase awareness of low-value care within endocrinology and suggest a path forward for addressing low-value care using principles of de-implementation science. [ABSTRACT FROM AUTHOR]

Background: The aesthetic and functional outcomes of the donor site following abdominal-based free flap breast reconstruction have been suboptimal. The objective of this study is to evaluate a modified liposuction-assisted abdominoplasty technique combined with rectus plication (LPARSP) adopted from cosmetic abdominoplasty practice. Patients and Methods: All abdominal-based free flap breast reconstructions from 01/2017 to 03/2019 were reviewed. Patients with central fullness and sufficient tissue surplus on the abdomen, thighs and flanks who received LPARSP and rectus plication were identified (LPARSP group) and matched for age and body mass index with patients who underwent conventional abdominoplasty (CA group). Abdominal skin sensation, objective functional and aesthetic measures of the abdomen, as well as patient-reported outcomes (Breast-Q), were analyzed. Results: A total of 28 patients were included. Groups were similar in demographics. The mean amount of lipoaspirate in the LPARSP group was 1054±613.5 ml. The postoperative course was similar in both groups. The LPARSP technique resulted in a lower positioned horizontal scar (p = 0.03). The aesthetic outcome was superior in the LPARSP group (p < 0.0001). Furthermore, the LPARSP group presented with a decreased bulging rate (p = 0.05), and secondary refinement procedures were less frequently demanded (p = 0.02). In addition, the abdominal wall sensation of the flanks was improved in the LPARSP group (p = 0.05), whereby patient-reported outcome measures did not differ between groups. Conclusions: Lipoabdominoplasty with rectus plication represents a safe approach for donor-site closure in selected patients undergoing abdominal-based free flap breast reconstruction. Superior functional and aesthetic results paired with improved abdominal wall sensation are achieved compared to CA. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body–mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk (p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations (p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM (p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association. [ABSTRACT FROM AUTHOR]

Thyroid disease is a very common condition that influences the entire human body, including cognitive function and mental health. As a result, thyroid disease has been associated with multiple neuropsychiatric conditions. However, the relationship between thyroid dysfunction and suicide is still controversial. We conducted a systematic review and meta-analysis to describe the association of thyroid function with suicidal behavior in adults. We searched four data bases (MEDLINE, EMBASE, PsycINFO, and Scopus) from their inception to 20 July 2018. Studies that reported mean values and standard deviation (SD) of thyroid hormone levels [Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3)] in patients with suicidal behavior compared with controls were included in this meta-analysis. The abstracts and papers retrieved with our search strategies were reviewed independently and in duplicate by four reviewers for assessment of inclusion criteria and data extraction, as well as for evaluation of risk of bias. Random-effects models were used in this meta-analysis to establish the mean difference on thyroid function tests between groups. Overall, 2278 articles were identified, and 13 studies met the inclusion criteria. These studies involved 2807 participants, including 826 participants identified with suicidal behavior. We found that patients with suicide behavior had lower levels of FT3 (−0.20 pg/mL; p = 0.02) and TT4 (−0.23 µg/dL; p = 0.045) compared to controls. We found no differences in either TSH, FT4, or TT3 levels among groups. With our search strategy, we did not identify studies with a comparison of overt/subclinical thyroid disease prevalence between patients with and without suicide behavior. The studies included in this meta-analysis had a low-to-moderate risk of bias. In the available literature, the evidence regarding the association of thyroid disorders and suicidal behavior is limited. We found that patients with suicidal behavior have significantly lower mean FT3 and TT4 levels when compared to patients without suicidal behavior. The clinical implications and pathophysiologic mechanisms of these differences remain unknown and further research is needed. [ABSTRACT FROM AUTHOR]

: Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Thyroid nodules are lumps of solid or liquid-filled tumors that form inside the thyroid gland, which can be malignant or benign. Our aim was to test whether the described features of the Thyroid Imaging Reporting and Data System (TI-RADS) could improve radiologists’ decision making when integrated into a computer system. In this study, we developed a computer-aided diagnosis system integrated into multiple-instance learning (MIL) that would focus on benign–malignant classification. Data were available from the Universidad Nacional de Colombia. Materials and Methods: There were 99 cases (33 Benign and 66 malignant). In this study, the median filter and image binarization were used for image pre-processing and segmentation. The grey level co-occurrence matrix (GLCM) was used to extract seven ultrasound image features. These data were divided into 87% training and 13% validation sets. We compared the support vector machine (SVM) and artificial neural network (ANN) classification algorithms based on their accuracy score, sensitivity, and specificity. The outcome measure was whether the thyroid nodule was benign or malignant. We also developed a graphic user interface (GUI) to display the image features that would help radiologists with decision making. Results: ANN and SVM achieved an accuracy of 75% and 96% respectively. SVM outperformed all the other models on all performance metrics, achieving higher accuracy, sensitivity, and specificity score. Conclusions: Our study suggests promising results from MIL in thyroid cancer detection. Further testing with external data is required before our classification model can be employed in practice. [ABSTRACT FROM AUTHOR]

Background: Levothyroxine (LT4) is one of the most commonly prescribed medications. Although considered a life-long replacement therapy, LT4 therapy can be discontinued for some patients. This study aims at: (i) reviewing the evidence on clinical outcomes of patients undergoing thyroid hormone replacement discontinuation, (ii) identifying the predictors of successful discontinuation, and (iii) systematically appraising frameworks used for deprescribing thyroid hormone. Methods: We searched multiple bibliographic databases, including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, from inception to February 2020 for studies in which thyroid hormone replacement was discontinued. Clinical outcomes assessed included: proportion of patients that remained euthyroid or needed to restart thyroid hormone replacement after discontinuation and frequency of clinical symptoms of hypothyroidism and adverse effects. We also evaluated predictors for discontinuation and deprescribing frameworks. Reviewers (F.J.K.T., N.B., N.M.S.O., S.M.) evaluated studies for inclusion, extracted data, and assessed methodological quality independently and in duplicate. Results: Seventeen observational studies at moderate to high risk of bias met inclusion criteria, including a total of 1103 patients (86% women) with an age range of 2–81 years. Approximately a third of patients undergoing thyroid hormone discontinuation remained euthyroid at follow-up (37.2%, 95% confidence interval [CI 24.2–50.1%], I2 97.5%). Subgroup analysis showed that patients with a previous diagnosis of overt hypothyroidism (OH) were less likely to remain euthyroid (11.8% [CI 0.4–23.2%], I2 90.3%) than patients with a prior diagnosis of subclinical hypothyroidism (SCH) (35.6% [CI 8.2–62.9%], I2 94.0%). No study followed a framework for systematically deprescribing LT4. Conclusions: Low-quality evidence suggests that up to a third of patients remained euthyroid after thyroid hormone discontinuation, with a higher proportion of patients with an initial diagnosis of SCH remaining euthyroid than patients with an initial diagnosis of OH. A deprescribing framework focusing on adequate selection of patients for deprescribing LT4 and a systematic process is warranted to guide clinicians in re-evaluating the need for LT4 in their patients. [ABSTRACT FROM AUTHOR]

Background: The use of prescribed medications during pregnancy is a challenge and an underestimated source of treatment burden. Levothyroxine (LT4) for the treatment of overt and subclinical hypothyroidism is extensively prescribed during pregnancy. To this end, we aimed to explore the patients' perceived benefits and risks, knowledge, beliefs, attitudes, and related burden of LT4 therapy during pregnancy. Methods: In this cross-sectional study, we surveyed pregnant women who were treated with LT4 during pregnancy from January 1, 2019, to December 31, 2019, in a tertiary academic medical center of the United States. The anonymous online survey included questions to gather demographic data and multiple-choice questions regarding the benefits and risks, knowledge, beliefs, attitudes, and burden related to LT4 use during pregnancy. Results: Sixty-four pregnant women (mean age 31.5 years) completed the study survey (response rate: 96%): 62% were diagnosed with hypothyroidism more than 12 months before pregnancy, 16% less than or about 12 months before pregnancy, and 22% during pregnancy. We found that one-third of pregnant women using LT4 had a feeling of uneasiness/anxiety due to their hypothyroidism diagnosis. About half of the respondents (45%) reported that they did not receive an explanation by their clinician regarding the maternal/fetal risks of uncontrolled hypothyroidism or the benefits of adequate control. Finally, two in three patients expressed various concerns of LT4-related treatment burden. Conclusions: Our findings support the need for increased effective communication and tailored counseling to address fears, anxiety, and uncertainties about the benefits and risks of LT4 use in pregnancy. For patients with clear benefits from LT4 treatment in pregnancy, it could help to overcome their concerns, promote adherence, and decrease adverse maternal/fetal outcomes. For patients with no clear benefits established, clinicians need to be aware of LT4-related treatment burden in pregnancy and implement patient-centered approaches in their clinical practices. [ABSTRACT FROM AUTHOR]

Iodine is a necessary micronutrient for the production of thyroid hormones and normal human development. Despite the significant worldwide strategies for the prevention and control of iodine deficiency, it is still a prevalent public health issue, especially in pregnant women. Severe iodine deficiency during pregnancy and neonatal period is associated with many major and irreversible adverse effects, including an increased risk of pregnancy loss and infant mortality, neonatal hypothyroidism, cretinism, and neuropsychomotor retardation. We will review the impact of severe iodine deficiency on maternofetal, neonatal, and offspring outcomes. We will also discuss its epidemiology, classification of iodine deficiency severity, and current recommendations to prevent iodine deficiency in childbearing age and pregnant women. [ABSTRACT FROM AUTHOR]

Purpose: To examine the proportion of diabetes-focused clinical encounters in primary care and endocrinology practices where the evaluation for hypoglycemia is documented; and when it is, identify clinicians' stated actions in response to patient-reported events. Methods: A total of 470 diabetes-focused encounters among 283 patients nonpregnant adults (≥18 years) with type 1 or type 2 diabetes mellitus in this retrospective cohort study. Participants were randomly identified in blocks of treatment strategy and care location (95 and 52 primary care encounters among hypoglycemia-prone medications (i.e. insulin, sulfonylurea) and others patients, respectively; 94 and 42 endocrinology encounters among hypo-treated and others, respectively). Documentation of hypoglycemia and subsequent management plan in the electronic health record were evaluated. Results: Overall, 132 (46.6%) patients had documentation of hypoglycemia assessment, significantly more prevalent among hypo-treated patients seen in endocrinology than in primary care (72.3% vs. 47.4%; P = 0.001). Hypoglycemia was identified by patient in 38.2% of encounters. Odds of hypoglycemia assessment documentation was highest among the hypo-treated (OR 13.6; 95% CI 5.5−33.74, vs. others) and patients seen in endocrine clinic (OR 4.48; 95% CI 2.3−8.6, vs. primary care). After documentation of hypoglycemia, treatment was modified in 30% primary care and 46% endocrine clinic encounters; P = 0.31. Few patients were referred to diabetes self-management education and support (DSMES). Conclusions: Continued efforts to improve hypoglycemia evaluation, documentation, and management are needed, particularly in primary care. This includes not only screening at-risk patients for hypoglycemia, but also modifying their treatment regimens and/or leveraging DSMES. [ABSTRACT FROM AUTHOR]

Background: Considerable uncertainty remains about the pattern of use of treatment options for Graves' disease (GD) and their comparative effectiveness and safety. Methods: Between 2005 and 2013, we identified patients with GD who received antithyroid drugs (ATDs), radioactive iodine (RAI) or surgery, and were represented in a large administrative data set in the United States (OptumLabs® Data Warehouse). Results: We identified 4661 patients with GD: mean age 48 (SD ±14) years, white (63%), and female (80%). Patients received ATD, n = 2817 (60%), RAI, n = 1549 (33%), or surgery, n = 295 (6%). Success rates were 50% for ATD, 93% for RAI, and 99% for surgery. Median time to treatment failure was 6.8 months for ATD and 3 months for RAI and surgery. When patients were required to be on ATD for at least one year before assessing failure, the failure rate decreased to 25%. Adverse effects occurred in 12% of patients receiving ATD, 6% with RAI, and 24% with surgery. Factors associated with treatment success were age >55 years (for ATD) and female sex (for RAI). About 12% of patients receiving ATD continued this treatment for >24 months as initial therapy. When patients failed ATD therapy, the most common second-line therapy was reinitiation of ATD (65%), RAI (26%), and surgery (9%). Overall, 26% of patients remain on ATD therapy (combined first or second line). Conclusions: ATD therapy was the most common GD therapy and demonstrated the lowest efficacy and infrequent significant adverse effect profile. With one fourth of patients remaining on ATD treatment (initial or second modality treatment), it becomes imperative to determine the long-term efficacy, safety, costs, and burdens of this modality of treatment. [ABSTRACT FROM AUTHOR]

Evidence regarding the effects of subclinical hypothyroidism (SCH) on adverse pregnancy outcomes and the ability of levothyroxine (LT4) treatment to prevent them is unclear. Available recommendations for the management of SCH during pregnancy are inconsistent. We conducted a nationwide survey among physicians assessing their knowledge of and current practices in the care of SCH in pregnancy and compared these with the most recent American Thyroid Association (ATA) recommendations. In this cross-sectional study, an online survey was sent to active US members of the Endocrine Society. This survey included questions about current practices and clinical scenarios aimed at assessing diagnostic evaluation, initiation of therapy, and follow-up in pregnant women with SCH. In total, 162 physicians completed the survey. ATA guidelines were reviewed by 76%, of whom 53% indicated that these guidelines actually changed their practice. Universal screening was the preferred screening approach (54%), followed by targeted screening (30%). For SCH diagnosis, most respondents (52%) endorsed a TSH level >2.5 mIU/L as a cutoff, whereas 5% endorsed a population-based cutoff as recommended by the ATA. The decision to initiate treatment varied depending on the specific clinical scenario; however, when LT4 was initiated, respondents expected a small/very small reduction in maternofetal complications. In conclusion, despite recently updated guidelines, there is still wide variation in clinical practices regarding the care of women with SCH in pregnancy. Highly reliable randomized trials are required to evaluate the effectiveness of the most uncertain treatment practices on the care of pregnant women with SCH. [ABSTRACT FROM AUTHOR]

Purpose: Fine-needle aspiration biopsy of the thyroid is an increasingly common outpatient procedure. Patients are counseled about the indications and risks of this procedure and informed consent is obtained. We aimed to assess the extent to which patients acquired necessary knowledge during this process.Methods: Survey study conducted in a thyroid nodule clinic at a referral center. Adult patients who had just undergone a thyroid biopsy were asked to complete a survey, including eight questions regarding the indications and potential outcomes of thyroid biopsy. The main outcome of the study was to assess the patients’ knowledge based on the response to each individual survey question.Results: Two-hundred and ninety-seven patients were eligible, of which 196 (66%) completed the survey: most were women (76%), had adequate reading health literacy (95%) and a mean age of 58 years. Although 86% of patients correctly identified evaluation for thyroid cancer as the main indication for their biopsy, 56% were not aware of the likelihood of this diagnosis. Almost all (>90%) of respondents knew that results could be benign or malignant; fewer were aware of non-diagnostic (71%) or indeterminate (68%) outcomes, or of the need for additional diagnostic testing after the biopsy (33%).Conclusions: After undergoing thyroid biopsy, a high proportion of well-educated patients remained unaware of their risk for thyroid cancer, potential outcomes, and downstream consequences of their biopsy. This quality gap raises the possibility that informed consent procedures that meet legal standards may leave patients undergoing thyroid biopsy paradoxically uninformed. [ABSTRACT FROM AUTHOR]

Objective Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography ( CT) and 18F-fluorodeoxyglucose (18FDG) positron emission tomography ( PET)/ CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. Design Retrospective cohort study. Methods Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. Results Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (−21-78) Hounsfield units ( HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value ( PPV) of 72% and negative predictive value ( NPV) of 100%. 18 FDG- PET/ CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake ( SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio ( ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG- PET/ CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. Conclusion Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG- PET/ CT could be considered as a second stage imaging study. [ABSTRACT FROM AUTHOR]