Toloza, Freddy J.K.

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.

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.

Objective Shared decision making (SDM) tools can help implement guideline recommendations for patients with atrial fibrillation (AF) considering stroke prevention strategies. We sought to characterize all available SDM tools for this purpose and examine their quality and clinical impact. Methods We searched through multiple bibliographic databases, social media, and an SDM tool repository from inception to May 2020 and contacted authors of identified SDM tools. Eligible tools had to offer information about warfarin and ≥1 direct oral anticoagulant. We extracted tool characteristics, assessed their adherence to the International Patient Decision Aids Standards, and obtained information about their efficacy in promoting SDM. Results We found 14 SDM tools. Most tools provided up-to-date information about the options, but very few included practical considerations (e.g., out-of-pocket cost). Five of these SDM tools, all used by patients prior to the encounter, were tested in trials at high risk of bias and were found to produce small improvements in patient knowledge and reductions in decisional conflict. Conclusion Several SDM tools for stroke prevention in AF are available, but whether they promote high-quality SDM is yet to be known. The implementation of guidelines for SDM in this context requires user-centered development and evaluation of SDM tools that can effectively promote high-quality SDM and improve stroke prevention in patients with AF.

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.

Background and objectives: It is unclear why many patients with hypothyroidism prefer the use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over levothyroxine (LT4) treatment, as recommended by clinical practice guidelines. We analyzed patient-reported information from patient online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. Materials and Methods: We conducted a mixed-methods study by evaluating the content of online posts from three popular hypothyroidism forums from patients currently taking DTE (n = 673). From these posts, we extracted descriptive information on patient demographics and clinical characteristics and qualitatively analyzed posts’ content to explore patient perceptions on DTE and other therapies further. Results: Nearly half (46%) of the patients reported that a clinician initially drove their interest in trying DTE. Patients described many reasons for switching from a previous therapeutic approach to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of side effects (22%). The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). The most frequently described benefits associated with DTE use were an improvement in symptoms (56%) and a change in overall well-being (34%). One-fifth of patients described side effects related to the use of DTE. Qualitative analysis of posts’ content supported these findings and raised additional issues around the need for individualizing therapy approaches for hypothyroidism (e.g., a sense of each patient has different needs), as well as difficulties obtaining DTE (e.g., issues with pharmacy availability). Conclusions: Lack of individualized treatment and a feeling of not been listened to were recurrent themes among DTE users. A subset of patients may prefer DTE to LT4 for many reasons, including perceived better effectiveness and improved overall well-being, despite the risks associated with DTE.

Abstract 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.