SAT519 Association of Free Thyroxine Level With Survival Outcome In Patients With Intermediate And High-Risk Differentiated Thyroid Cancer
Authors: Ghosh Raisa , Auh Sungyoung , Gubbi Sriram , Veeraraghavan Padmasree , Cochran Craig , Shobab Leila , Burman Kenneth D , Wartofsky Leonard , Klubo-Gwiezdzinska Joanna 
Published: October 2023

Abstract
Disclosure: R. Ghosh: None. S. Auh: None. S. Gubbi: None. P. Veeraraghavan: None. C. Cochran: None. L. Shobab: None. K.D. Burman: None. L. Wartofsky: None. J. Klubo-Gwiezdzinska: None.
Background Total thyroidectomy followed by radioiodine (RAI) is a standard treatment for patients with intermediate and high-risk differentiated thyroid cancer (DTC). Long-term management consists of therapy with supraphysiologic doses of levothyroxine to suppress thyrotropin (TSH), as in vitro models have shown that TSH can act as a differentiation signal at physiologic concentrations, but as cancer proliferating stimulus in higher concentrations. On the other hand, preclinical studies have shown that thyroid hormones (T4/T3) can act as a growth stimulus in thyroid cancer cell lines. Moreover, supraphysiologic doses of T4/T3 are associated with an increased risk of atrial fibrillation and osteoporotic fractures. There are limited data on the role of elevated free T4 (FT4) on survival outcomes in patients with DTC. The goal of this study was to assess the association between FT4 levels and progression-free survival (PFS) in patients with intermediate-to-high-risk DTC. Material and Methods This cohort study was approved by the multi-institutional review board. Patients with DTC treated uniformly with total thyroidectomy and RAI between January 1, 1979, and March 1, 2015, and subjected to TSH suppression therapy, with at least 3 TSH and FT4 values available over time were included. The association between average FT4 level above the upper reference range (&gt;1.8 ng/dl) at landmarks 6, 12, and 18 months was assessed by Kaplan-Meier survival curves. A Cox proportional hazards model was used to assess the contribution of competing risks such as age, sex, tumor size, lymph node, and distant metastases on PFS. Results The study included 382 patients, aged 46.6 ± 16.5 years, 245/382 (64.1%) women, treated with a median RAI dosage of 159 (110-410) mCi and followed for 8.5±6.2 years during which 132/382 (34.5%) experienced disease progression. During follow-up, 108/382 (28.3%) patients presented with an average FT4 of &gt;1.8 ng/dl, while the remaining patients had FT4 within the normal range. Overall, elevated FT4 level was not associated with decreased PFS (HR 0.9, CI 0.54 -1.5, p=0.69), while age at diagnosis (HR 1.02, CI 1.004-1.04, p=0.01), tumor size (HR 1.15, CI 1.04 -1.28, p=0.01), lateral neck lymph node metastases (HR 2.9, CI 1.78 - 4.74, p&lt;0.001), bone metastases (HR 4.87, CI 1.79 - 13.3, p=0.002) and brain metastases (HR 5.56, CI 2.54 - 12.2, p&lt;0.001) were associated with shorter PFS. The landmark analysis performed to reduce the bias due to time-varying covariates at 6, 12, and 18 months confirmed these results. Conclusions Although high FT4 may stimulate thyroid cancer growth in vitro, elevated FT4 levels do not appear to worsen PFS. However, in managing patients with persistent DTC, clinicians must balance the benefits of TSH suppression with the potential detrimental effects of high FT4 on cardiovascular and bone health.
Presentation Date: Saturday, June 17, 2023