Thyroid Hormone Withdrawal Yields Higher ¹³¹ I Absorbed Dose to Metastases Than rhTSH Stimulation in Differentiated Thyroid Cancer: Evidence from a Large ¹²⁴ I PET/CT Dosimetry Cohort

Achieving an optimal ¹³¹I absorbed dose in differentiated thyroid carcinoma lesions is crucial for the success of radioiodine therapy. Sufficient thyroid-stimulating hormone (TSH) stimulation before radioiodine therapy can be achieved with either thyroid hormone withdrawal (THW) or by injection of recombinant human TSH (rhTSH). We compared the predicted ¹³¹I lesion absorbed dose between THW and rhTSH stimulation in patients assessed by pretherapeutic ¹²⁴I PET/CT dosimetry. <b>Methods:</b> This retrospective study included patients with differentiated thyroid carcinoma who had undergone total thyroidectomy with or without cervical lymph node dissection and had received ¹²⁴I PET/CT lesion dosimetry. All patients underwent TSH stimulation with either rhTSH injection or THW. For lesion dosimetry, 2 ¹²⁴I PET/CT examinations were performed after ¹²⁴I administration. Using ¹²⁴I PET data, the lesion absorbed dose per unit of administered activity (LDpA) of ¹³¹I was calculated for each lesion. Patients and lesions were categorized by the TSH stimulation method used and the clinical indication for dosimetry (adjuvant, residual/recurrent, or metastatic disease). Lesions were further categorized by location (thyroid remnants, cervical lymph node metastases, or distant metastases). <b>Results:</b> In total, 453 dosimetry cycles and 949 lesions were analyzed in 367 patients. TSH levels were significantly higher after rhTSH stimulation in the overall patient group (<i>P</i> < 0.001) and across all subgroups (<i>P</i> = 0.038 for adjuvant; <i>P</i> = 0.002 for residual/recurrent; <i>P</i> < 0.001 for metastatic). Thyroglobulin levels were significantly elevated after rhTSH stimulation in both the overall patient group (<i>P</i> < 0.001) and the metastatic subgroup (<i>P</i> = 0.030). LDpA values were significantly higher after THW in the overall patient group (<i>P</i> < 0.001) and in the adjuvant subgroup (<i>P</i> = 0.049). LDpA values of thyroid remnants did not significantly differ between both stimulation methods. Conversely, LDpA values were significantly higher after THW in cervical lymph node (<i>P</i> = 0.005) and distant (<i>P</i> = 0.001) metastases. <b>Conclusion:</b> As assessed by pretherapeutic ¹²⁴I PET/CT dosimetry, absorbed doses to metastatic lesions were higher after THW compared with rhTSH, whereas absorbed doses of thyroid remnants were comparable between both stimulation methods. In this interpatient comparison, data support the use of THW in patients with an elevated risk of metastatic disease; however, a large intrapatient study is warranted for further validation.