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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]

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: 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]

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]

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]