Desiccated Thyroid Extract Combined With Levothyroxine for TSH Suppression Therapy in DTC

Summary

The global incidence of Differentiated Thyroid Cancer (DTC) is rising. While surgery followed by TSH suppression is the standard of care, achieving target TSH levels with levothyroxine (L-T4) monotherapy remains challenging, with only 25-70% of intermediate/high-risk patients attaining it within 6-8 months. This therapeutic dilemma stems from three key issues: impaired T4-to-T3 conversion due to DIO2 polymorphisms, the non-physiological hormone ratio of T4 monotherapy, and L-T4's narrow therapeutic window. This often results in an "under- versus over-suppression" paradox, increasing risks of recurrence, atrial fibrillation, and osteoporosis. Combining L-T4 with desiccated thyroid extract (DTE; T4:T3 ≈ 4:1) may overcome these limitations by bypassing DIO2 defects and providing a more physiological hormone profile, thereby potentially improving TSH control while mitigating side effects. Supported by the 2023 Chinese guidelines and our promising pilot data (82% cumulative target attainment at a median of 1.4 months), we propose a two-stage national study: a multicenter cohort study followed by a randomized trial, to generate high-level evidence for this combination therapy in high-risk DTC.

Timeline

Start

2025-11-30

Primary completion

2027-11-30

Completion

2028-06-30

Publications

• Results Turner, H.L., van Etten, J., Firth, D. et al. Modelling rankings in R: the PlackettLuce package. Computational Statistics.2020; 35(3): 1027-1057.
• Results Fussey JM, Khan H, Ahsan F, Prashant R, Pettit L. Thyroid-stimulating hormone suppression therapy for differentiated thyroid cancer: The role for a combined T3/T4 approach. Head Neck. 2017 Dec;39(12):2567-2572. doi: 10.1002/hed.24926. Epub 2017 Sep 27.
• Results Hao D, Tian L, He H, Zhu C, Guo L, Zhang K, Zhang J. Efficacy and safety of postoperative levothyroxine sodium tablets for improving serum thyroid hormone levels and tumor marker levels in patients with thyroid tumors. Eur J Transl Myol. 2023 Sep 5;33(3):11582. doi: 10.4081/ejtm.2023.11582.
• Results Wang Z, Angell TE, Sun W, Qin Y, He L, Dong W, Zhang D, Zhang T, Shao L, Lv C, Zhang P, Guan H, Zhang H. Analysis of the strategy of LT4 prescribing and TSH monitoring for thyroid carcinoma after lobectomy. Ann Transl Med. 2020 Oct;8(19):1238. doi: 10.21037/atm-20-4890.
• Results Chen W, Li J, Peng S, Hong S, Xu H, Lin B, Liang X, Liu Y, Liang J, Zhang Z, Ye Y, Liu F, Lin C, Xiao H, Lv W. Association of Total Thyroidectomy or Thyroid Lobectomy With the Quality of Life in Patients With Differentiated Thyroid Cancer With Low to Intermediate Risk of Recurrence. JAMA Surg. 2022 Mar 1;157(3):200-209. doi: 10.1001/jamasurg.2021.6442.
• Results Ming J, Zhu JQ, Zhang H, Sun H, Wang J, Cheng RC, Xie L, Li XR, Tian W, Huang T. A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study). BMC Endocr Disord. 2021 Oct 21;21(1):208. doi: 10.1186/s12902-021-00871-x.
• Results Yavuz DG, Yazan CD, Hekimsoy Z, Aydin K, Gokkaya N, Ersoy C, Akalin A, Topaloglu O, Aydogan BI, Dilekci ENA, Alphan Uc Z, Cansu GB, Ozsari L, Iyidir OT, Olgun ME, Keskin L, Mert M, Can B, Gungor K, Galip T, Canturk Z, Elbuken G, Pekkolay Z, Kutbay NO, Yorulmaz G, Kalkan AT, Unsal YA, Yay A, Karagun B, Bozkur E. Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients. Clin Endocrinol (Oxf). 2022 Dec;97(6):833-840. doi: 10.1111/cen.14787. Epub 2022 Jun 12.
• Results Ku EJ, Yoo WS, Lee EK, Ahn HY, Woo SH, Hong JH, Chung HK, Park JW. Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2021 Nov 19;106(12):3655-3667. doi: 10.1210/clinem/dgab539.
• Results Ringel MD, Sosa JA, Baloch Z, Bischoff L, Bloom G, Brent GA, Brock PL, Chou R, Flavell RR, Goldner W, Grubbs EG, Haymart M, Larson SM, Leung AM, Osborne JR, Ridge JA, Robinson B, Steward DL, Tufano RP, Wirth LJ. 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid. 2025 Aug;35(8):841-985. doi: 10.1177/10507256251363120.
• Results Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S, Dal Maso L. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 2021 Apr;9(4):225-234. doi: 10.1016/S2213-8587(21)00027-9. Epub 2021 Mar 1.

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