7445 The Effect of Combination Thyroid Hormone Therapies on Symptoms in Patients with a Suboptimal Response to Levothyroxine: A Post-Hoc Analysis

Abstract Disclosure: A.A. Patel: None. M.K. Shakir: None. F. Tuamokumo: None. A.C. Bianco: None. T.D. Hoang: None. The standard treatment of hypothyroidism is levothyroxine (LT4). Combination therapies such as desiccated thyroid extract (DTE) or LT4 + liothyronine (LT3) are used much less. There is now evidence that combination therapies are effective and safe if serum thyroid stimulating hormone (TSH) is kept within a normal range. We studied whether there is a role for combination therapies specifically in hypothyroid patients who remain symptomatic despite biochemical evidence of adequate treatment with LT4, an issue that remains a challenging clinical conundrum for clinicians and patients alike. We conducted a post-hoc analysis of a prospective, randomized, double-blind, cross-over study of 75 patients with hypothyroidism performed at our institution. Patients were originally allocated to 1 of 3 treatment arms (LT4: Group A, DTE: Group B, or LT4+LT3: Group C) for 22 weeks and then crossed-over to the other two treatment arms sequentially for 22 weeks at a time until they had completed all treatment regimens. The Thyroid Symptom Questionnaire (TSQ) was completed by all patients during the initial study (a set of 12 questions with a total point range of 0-36; a higher score indicates more symptoms). We stratified patients by their TSQ score while on LT4 into three quantiles: Category 1 (TSQ 0-12; n=23), Category 2 (TSQ 13-24; n=42), Category 3 (TSQ 25-36; n=10). Differences were detected with a one-way ANOVA test and the Tukey multiple comparison post-test. No significant difference was found among treatment groups in Category 1 (p=0.063). In Category 2, the DTE group had significantly lower TSQ scores than the LT4 group (mean LTE score 18.9, SD 3.7; mean DTE score 14.3, SD 6.9; p=0.026). In Category 3, the LT4+LT3 group had significantly lower scores than LT4 and DTE groups (mean LTE score 27.7, SD 2.4; mean DTE score 23.1, SD 8.7; mean LT4+LT3 score 15.8, SD 4.7; p<0.001 LT4+LT3 vs LT4; p=0.026 LT4+LT3 vs DTE). This study demonstrates that patients with hypothyroidism who remain symptomatic while on LT4 may benefit from use of combination therapies such as DTE or LT4+LT3. Patients who generally have minimal residual symptoms with LT4 are unlikely to have significant symptomatic improvement on combination therapies. In addition, patients with moderate severity symptoms (TSQ 13-24) on LT4 had significant symptomatic improvement with DTE and patients with the most severe symptoms (TSQ 25-36) on LT4 had significant symptomatic improvement with LT4+LT3. No single TSQ question was more sensitive or prevalent in groups 2 and 3 (the most symptomatic groups). The results suggest a potential clinical role for combination therapies such as DTE and LT4+LT3 in patients who do not have improvement in hypothyroid symptoms on LT4 (TSQ score >13). Presentation: 6/3/2024