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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.

Assess the effect of intensive vs conventional blood pressure goals on patient-important outcomes in older adults with type 2 diabetes.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.Seven trials were included. A 19% risk reduction (OR 0.81; 95% CI 0.69-0.95; IIntensive 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.

Address treatment burden and general perceptions of pharmacological treatment in patients with diabetes.We surveyed adult patients with diabetes cared for in a tertiary academic medical center about: i) knowledge about the impact of glucose-lowering medication use on diabetes control and complications, ii) common beliefs about natural medicine and insulin use, iii) attitudes towards glucose-lowering medications, iv) burden of treatment, v) general knowledge of diabetes pharmacological treatment, and vi) perceptions of shared decision-making.Two hundred-four participants completed the survey. While most (90%) agreed that adherence to medication would control diabetes and improve quality of life, 30-40% were not certain that it would translate to fewer disease complications. About one of three thought medications could be harmful (29.4%). Over 50% agreed or was unsure that natural remedies were as good/better than prescribed medications. About 30% acknowledged difficulties taking their diabetes medications and monitoring blood glucose, and over 50% were concerned about treatment costs. Nearly 30% denied receiving a detailed explanation from their clinician regarding their disease and is treatment.Our results highlight the importance of patient education regarding pharmacological treatment for diabetes, and eliciting sources of distress and treatment burden among patients with diabetes.

Among pregnant women on thyroid hormone replacement therapy undertreatment is common, while overtreatment is rare. Both deficient and excessive maternal thyroid hormone have been related to adverse maternofetal and long-term offspring outcomes, although studies' results are inconsistent. This review aims to discuss recent evidence regarding the effects of under- and overtreatment with thyroid hormone replacement during pregnancy and how current practices could be improved.Whether or not thyroid hormone therapy needs to be initiated for maternal subclinical hypothyroidism remains unclear, but recent meta-analyses have confirmed associations between adverse maternal, neonatal, and offspring outcomes in both overt and subclinical hypothyroidism. Subclinical hyperthyroidism in pregnancy is related to fewer adverse outcomes. Current adherence to levothyroxine during pregnancy and medication counseling by healthcare providers are suboptimal.Undertreatment of maternal hypothyroidism may increase risks for adverse maternofetal and offspring effects more than overtreatment does. If thyroid hormone replacement therapy is indicated and initiated in pregnancy, frequent thyroid function monitoring is required to avoid under- or overtreatment. Effective communication between clinicians and patients is imperative to increase medication adherence.

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.

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.

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.

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.

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.

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.

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. 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. 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

Introduction Closed incision negative-pressure therapy (CINPT) has been shown to shorten the time to heal in post-bariatric abdominoplasty and to lower seroma rates in cosmetic abdominoplasty. The objective of this study was to assess the effect of CINPT on donor-site morbidity following abdominal-based free-flap breast reconstruction. Patients and methods We reviewed medical records from 225 women who had undergone 300 microsurgical free-flap breast reconstructions from the abdomen from November 1, 2007 to March 31, 2019. Patients were grouped according to wound therapy, including 127 patients in the standard of care group and 98 patients in the CINPT group. Primary outcomes were minor (non-operative) and major (operative) surgical site complications. Secondary outcomes were time to drain removal, in-hospital length, and scar quality. Results Analysis of patient demographics showed an equal distribution with regard to the age, smoking status, prevalence of diabetes mellitus, preoperative chemotherapy, and previous abdominal surgery in both groups. Significantly more patients with obesity (29.6 vs. 15.8%; p = .01) and bilateral breast reconstruction (40.8 vs. 27.6%; p = .04) were included in the CINPT group. Compared to standard of care, the CINPT group had a lower incidence of major surgical site complications (26.0 vs. 11.2%; p = .001). There was no difference in minor surgical site complications and secondary outcomes between groups. Conclusion The CINPT represents a reliable tool to reduce surgical site complications on the abdominal donor-site in abdominal-based free-flap breast reconstruction.

To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.The authors conducted a comprehensive search from databases' inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormonelsqb;TSH], free thyroxinelsqb;FT4], free triiodothyroninelsqb;FT3], total T4lsqb;TT4], and total T3lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P.00001) compared with controls. Conversely, patients with non-combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.

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, w...

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.

BACKGROUND: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. METHODS: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT(4)), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. FINDINGS: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT(4) concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT(4) concentrations were not associated with the outcomes measured. INTERPRETATION: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. FUNDING: Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.

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.

Subclinical hypothyroidism (SCH) is a common diagnosis among women of reproductive age. The importance of sufficient maternal thyroid supply during pregnancy is well known. Nevertheless, the effects of SCH during pregnancy and the efficacy of its treatment on maternofetal outcomes are not well established. This review discusses the recent evidence on SCH in pregnancy and how this evidence is reflected in current clinical care.Recent observational studies have found a positive association between SCH during pregnancy and adverse maternal, neonatal and offspring outcomes, mainly in thyroid peroxidase autoantibody positive women. Although interventional studies have shown a benefit of levothyroxine (LT4) treatment on selected pregnancy outcomes, there was no effect on offspring neurodevelopment.Current evidence strengthens the association between SCH with both maternofetal and offspring adverse outcomes. An earlier and more individualized diagnostic assessment taking into consideration predictors of thyroid dysfunction and major risk factors for complications could result in better management of SCH during pregnancy. The effectiveness of LT4 on improving maternofetal and long-term offspring outcomes is still not fully elucidated.

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.

Background Hypertension is a major cardiovascular risk factor that affects over 50% of individuals with type 2 diabetes. Lowering blood pressure to reduce the risk of micro- and macrovascular complications of diabetes is a strong recommendation advocated by contemporary clinical practice guidelines, however, proposed goals for older patients with diabetes are heterogeneous and rely on indirect evidence as they are frequently underrepresented in clinical trials. Herein, the optimal blood pressure goal and its associated risks remain uncertain in this population. Objective To 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 MEDLINE, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled trials, and Cochrane Database of Systematic Reviews, from database inception to March 2021. Randomized controlled trials comparing intensive vs conventional blood pressure goals in adults over 60 years of age with type 2 diabetes were included. Screening and data extraction were performed independently and in duplicate. Modified Mantel-Haenszel meta-analyses were conducted to estimate odds ratios (OR) for dichotomous outcomes and mean differences for continuous outcomes, alongside 95% confidence intervals (CIs). (PROSPERO registration number: CRD42019126078) Results Seven trials fulfilled our inclusion criteria.A 19% risk reduction (OR 0.81; 95% CI 0.69 to 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 to 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 were scarcely reported among included studies. Conclusion In summary, our analysis provides evidence that intensive blood pressure goals in older patients with diabetes are associated with a lower risk of stroke and MACE. Nevertheless, data are very scarce regarding microvascular diabetes outcomes and treatment safety. Given that an intensive approach would increase the number of medications, cost, adverse events and probably decrease adherence, treatment of hypertension in this population should be conducted with a shared decision making approach that makes sense from an intellectual, emotional, and practical basis. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

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.

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.

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.

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.

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%], I(2) 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%], I(2) 90.3%) than patients with a prior diagnosis of subclinical hypothyroidism (SCH) (35.6% [CI 8.2–62.9%], I(2) 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.

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.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.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.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.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 .