Ambrogini, Elena

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>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

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.