Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.

Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts.

PURPOSE: Selenium, incorporated into specific seleno-enzymes, is essential to proper thyroid function and protect cells from oxidative damage induced by H2O2 during thyroid hormone synthesis. Several studies indicated that low selenium levels are associated with thyroid autoimmunity and related disorders, but real effectiveness of selenium supplementation in such diseases is still controversial. We evaluated the effect of selenium on oxidative damage in human thyrocytes and thyroid fibroblasts in vitro. METHODS: To induce oxidative stress, primary cultures were exposed to H2O2, in the presence or the absence of selenium, as either selenomethionine or selenite. We performed the following assays: cell viability, caspase-3 activity, BCL-2/BAX gene expression, DNA fragmentation, malondialdehyde levels, and glutathione peroxidase (GPx) activity measurements. RESULTS: Thyrocytes and thyroid fibroblasts exposed to H2O2 and preincubated with both selenocompounds displayed a significant dose-dependent increase in cell viability compared to cells incubated with H2O2 alone. Pretreatment with selenomethionine and selenite significantly reduced caspase-3 activity and BAX mRNA levels and increased BCL-2 mRNA levels in a dose-dependent manner. Accordingly, H2O2 induced a diffuse pattern of DNA degradation and an increase in malondialdehyde levels, which was prevented by the pretreatment with both selenomethionine and selenite. Both selenocompounds induced an increase in GPx activity, suggesting that these protective effects may be, almost in part, mediated by these selenoproteins. CONCLUSION: In human thyrocytes and fibroblasts in vitro, selenium exerts protective effects against H2O2 in a dose-dependent manner, being selenite effective at lower doses than selenomethionine.

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

PURPOSE: In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. METHODS: We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. RESULTS: The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. CONCLUSIONS: DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.