Context No consensus exists about the optimal duration of the low iodine diet (LID) in preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. Objective This work aimed to investigate if a LID of four days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. Methods In this prospective study, 65 DTC patients treated in two University Medical Centers were included between 2018 and 2021. The patients collected 24-h urine on day four and seven of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-h urinary iodine excretion (UIE) on both days. Results The median 24-h UIE on day four and day seven of the LID were not significantly different (36.1[IQR 25.4 – 51.2]mcg and 36.5[IQR 23.9 – 47.7]mcg, respectively, P=0.43). On day four of the LID, 72.1% of the DTC patients were adequately prepared (24-h UIE<50 mcg), and 82.0% of the DTC patients on day seven(P=0.18). Compared to the self-reported regular diet, DTC patients showed a significantly(P<0.01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. Conclusions The 24-h UIE on day four of the LID did not differ from day seven, and therefore shortening the LID from seven to four days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

Background: During treatment for differentiated thyroid carcinoma (DTC), patients go from euthyroidism to severe hypothyroidism to subclinical hyperthyroidism induced by thyroid hormone suppression therapy (THST). Severe hypothyroidism may induce a tendency toward bleeding, whereas hyperthyroidism is thrombogenic. Therefore, treatment for DTC may increase the risk of bleeding during thyroid hormone withdrawal, and thrombosis during THST. This study aims to provide prospective analysis of changes in the hemostatic system from euthyroidism to hypothyroidism, and during THST, in patients treated for DTC. Methods: This is a secondary study in a larger Dutch prospective cohort. Consecutive samples were obtained from 20 patients (18 female [90%]; median age 48 [interquartile range 35.8-56.5] years) throughout their treatment for DTC during euthyroidism (n = 5), severe hypothyroidism (n = 20), and THST (n = 20). We measured selected hemostatic proteins and C-reactive protein (CRP), performed functional tests of hemostasis (a thrombin generation test and a plasma-based clot lysis test), and assessed markers of in vivo activation of hemostasis (thrombin-antithrombin complexes, plasmin-antiplasmin [PAP] complexes, and D-dimer levels). Results: During hypothyroidism, the majority of measured parameters did not change. During THST, plasma levels of nearly all measured hemostatic proteins were higher than during hypothyroidism. Additionally, CRP significantly increased from 1.3 (0.5-3.3) to 3.2 (1.3-5.1) mg/L during THST ( p < 0.01). Ex vivo thrombin generation increased from 626.0 (477.0-836.3) to 876.0 (699.0-1052.0) nM • min ( p = 0.02), and ex vivo clot lysis time increased from 60.6 (55.6-67.4) to 76.0 (69.7-95.0) minutes during THST ( p < 0.01). PAP levels reduced from 266.5 (211.8-312.0) to 192.0 (161.0-230.0) lg/L during THST ( p < 0.01); other markers of in vivo activation of coagulation remained unaffected. Conclusions: During THST-induced hyperthyroidism, a shift toward a more hypercoagulable and hypofibrinolytic state occurred. However, in vivo activation of hemostasis did not increase. The rise in CRP levels suggests the presence of a low-grade inflammation in patients during THST. Both a hypercoagulable and hypofibrinolytic state and a low-grade inflammation are associated with an increased risk of cardiovascular diseases (CVD). Therefore, the subtle changes found during THST could potentially play a role in the pathogenesis of CVD as observed in DTC patients. Clinical Trial Registration: This study is part of a larger clinical trial registered at the Netherlands Trial Register (NTR ID 7228).