Owen, Richard R.

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 Disclosure: S. Maraka: None. R. Owen: None. N.M. Singh Ospina: None. M. Knox: None. T. Dodds: None. H. Spencer: None. A. Albashaireh: None. A. Shah: None. S. Syed: None. S. Naqvi: None. H. Motahari: None. S. Thumma: None. E. Ambrogini: None. J.P. Brito: None. Objective: Levothyroxine (LT4) therapy has not been shown to improve quality of life (QoL), thyroid-related symptoms, cardiovascular events, or mortality for patients with subclinical hypothyroidism (SCH) in clinical trials. We conducted this pilot, double-blind, placebo-controlled clinical trial to evaluate the effects of LT4 discontinuation among adults with SCH. Methods: We aimed to randomize 50 adults 1:1 to continue receiving LT4 (25-75 mcg/day) for SCH or discontinue it (switch to placebo). The primary outcome was feasibility. Secondary outcomes included changes in QoL measures (Thyroid-specific QoL Patient-Reported Outcome [ThyPRO]-Hypothyroid Symptoms and Tiredness scores, EuroQoL 5-Dimension Self-Report Questionnaire [EQ-5D]) assessed at baseline and 6 months post-randomization, and incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, stroke, acute coronary syndrome, heart failure, fracture, mortality). Higher scores for ThyPRO indicate more symptoms and tiredness and for EQ-5D, better health state. Data are reported as mean (standard deviation). Analysis of covariance model adjusting for age and baseline measure of the variable was performed for the outcomes based on the intention-to-treat principle. Results: Fifty participants were enrolled (33% recruitment rate); 24 were randomized to the LT4 and 26 to the discontinuation group. Five patients were excluded post-randomization due to lack of ascertainment of SCH diagnosis (final N=45; 21 LT4, 24 discontinuation). There was no statistically significant difference at baseline between the discontinuation and LT4 groups in age [65.7 (10.6) vs. 71.0 (7.9) yrs], gender (male 75 vs. 86%), LT4 dose (25 mcg; 29.2 vs. 33.3%, 50 mcg; 54.2 vs. 47.6%, 75 mcg; 16.7 vs. 19.0%), TSH [3.1 (1.0) vs. 3.2 (1.4) mIU/L], TPOAb positivity (17 vs. 19%), ThyPRO-Hypothyroid Symptoms [27.1 (20.4) vs. 21.1 (18.4)] and Tiredness score [33.2 (23.7) vs. 31.1 (23.9)], and EQ-5D [0.746 (0.229) vs. 0.758 (0.193)]. A patient in the discontinuation group withdrew for personal reasons (98% completion rate). Two patients in the discontinuation group met study criteria to restart LT4 (TSH&gt;10 mIU/L; n=1, fatigue; n=1). At final visit, 34.8% of patients in the discontinuation group had mild SCH compared to 9.5% of patients on LT4 (p=0.07). There was no statistically significant difference between the discontinuation and LT4 groups in ThyPRO-Hypothyroid Symptoms [28.3 (22.8) vs. 22.9 (19.5)], Tiredness [27.6 (22.8) vs. 32.8 (22.1)], and EQ-5D score [0.750 (0.232) vs. 0.741 (0.180)]. A patient suffered rib fracture (placebo); no other adverse event of interest was reported. Conclusion: This pilot clinical trial showed the feasibility and safety of discontinuing LT4 in patients with SCH. These findings support proceeding with a larger multi-site clinical trial to fully assess the effects of LT4 discontinuation. Presentation: Thursday, June 15, 2023

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.