Rosália P. Padovani

One Month Is Sufficient for Urinary Iodine to Return to Its Baseline Value After the Use of Water-Soluble Iodinated Contrast Agents in Post-Thyroidectomy Patients Requiring Radioiodine Therapy

BACKGROUND There is a concern regarding the use of iodinated contrast agents (ICA) for chest and neck computed tomography (CT) to localize metastatases in patients with differentiated thyroid cancer (DTC). This is because the iodine in ICA can compete with (131)I and interfere with subsequent whole scans or radioactive iodine treatment. The required period for patients to eliminate the excess iodine is not clear. Therefore, knowing the period for iodine levels to return to baseline after the injection of ICA would permit a more reliable indication of CT for DTC patients. The most widely used marker to assess the plasmatic iodine pool is the urinary iodine (UI) concentration, which can be collected over a period of 24 hours (24U) or as a single-spot urinary sample (sU). As 24U collections are more difficult to perform, sU samples are preferable. It has not been established, however, if the measurement of iodine in sU is accurate for situations of excess iodine. METHODS We evaluated 25 patients with DTC who received ICA to perform chest or neck CT. They collected 24U and sU urinary samples before the CT scan and 1 week and 1, 2, and 3 months after the test. UI was quantified by a semiautomated colorimetric method. RESULTS Baseline median UI levels were 21.8 μg/dL for 24U and 26 μg/dL for sU. One week after ICA, UI median levels were very high for all patients, 800 μg/dL. One month after ICA, however, UI median levels returned to baseline in all patients, 19.0 μg/dL for 24U and 20 μg/dL for sU. Although the values of median UI obtained from sU and 24U samples were signicantly different, we observed a significant correlation between samples collected in 24U and sU in all evaluated periods. CONCLUSION One month is required for UI to return to its baseline value after the use of ICA and for patients (after total thyroidectomy and radioiodine therapy) to eliminate the excess of iodine. In addition, sU samples, although not statistically similar to 24U values, can be used as a good marker to evaluate patients suspected of contamination with iodine.

Even Without Additional Therapy, Serum Thyroglobulin Concentrations Often Decline for Years After Total Thyroidectomy and Radioactive Remnant Ablation in Patients with Differentiated Thyroid Cancer

BACKGROUND Current management guidelines suggest that 6-12 months after total thyroidectomy and radioactive iodine remnant ablation (RAI-RA), patients with differentiated thyroid cancer should be re-evaluated with serum thyroglobulin (Tg) and neck ultrasonography to assess the efficacy of initial treatment and to guide subsequent management. However, if serum Tg levels can continue to decline for many years after RAI-RA, then an early assessment of response to therapy could lead to excessive evaluations and treatments in patients with low-level Tg values that are likely to resolve over time without additional therapies. METHODS Serum Tg concentrations in patients with differentiated thyroid cancer, who had been thyroidectomized (Tx), received RAI-RA, and who were receiving levothyroxine to suppress serum thyrotropin (suppressed serum Tg), were retrospectively analyzed. The study included 299 patients, 69% of whom were women with an overall median age of 46 years and who had a median follow-up of 7 years. The study was limited to patients who received no additional treatments beyond total Tx, RAI-RA, and levothyroxine therapy to suppress thyrotropin. The primary endpoints were the time required to achieve the lowest Tg (nadir Tg) and the time required to achieve a suppressed serum Tg<1 ng/mL. RESULTS The nadir -suppressed serum Tg was achieved by 6 months in 58% of the patients and by 12 months in 75% of the patients. The remaining 25% of patients required 18 months or longer to reach the nadir Tg. However, in the subgroup of patients that eventually reached a nadir suppressed serum Tg<1 ng/mL (n=223 patients), this goal was achieved by 6 months in 81%, by no more than 12 months in 91%, and by no more than 18 months in 94%. In patients with a 6-month suppressed serum Tg of 1-5 ng/mL, 54% eventually developed a suppressed serum Tg of <1 ng/mL without additional therapy. CONCLUSIONS In patients selected for continued observation, serum Tg levels often continue to decline for several years after total Tx and RAI-RA. While a 6-12-month assessment of the response to initial therapy is useful in patient management, strong consideration should be given to continued observation without additional therapy in patients with well-differentiated thyroid cancer who have 6-month suppressed serum Tg values of 1-5 ng/mL without a structurally identifiable disease.

Lithium as an adjuvant in the postoperative ablation of remnant tissue in low-risk thyroid carcinoma.

BACKGROUND Thyroid remnant ablation (RA) with 30 mCi of radioactive iodine (131I) in patients thyroidectomized for treatment of low-risk differentiated thyroid carcinoma (DTC) has a success rate of 64% to 84%. Lithium increases the residence time of 131I in the thyroid tissue. The aim of this study was to determine if lithium treatment added to 30 mCi 131I would enhance the success rate of this treatment compared with 30 mCi 131I alone in patients who were thyroidectomized for treatment of low-risk DTC. METHODS This was a randomized study with endpoint at one year. Sixty one consecutive patients were enrolled and randomized into two groups: group A (n=32) treated with 30 mCi 131I; group B (n=29) treated with 30 mCi 131I plus an oral dose of lithium 900 mg/day, for 7 days. All patients were evaluated by whole body scan (WBS) with 123I and had serum TSH, thyroglobulin (Tg), and anti-Tg antibodies (TgAb) determined when they were hypothyroid on no thyroid hormone. Patients were reevaluated after one year with serum TSH, Tg, and TgAb determinations and WBS with 123I. The criteria for defining a successful outcome was a negative WBS and a serum Tg of <1. RESULTS Group A was composed of 28 women and four men (ages 25-71 years) with 2 having follicular thyroid carcinoma (FTC), 22 having papillary thyroid carcinoma (PTC) of 1-4.5 cm, and 8 having micro PTCs (mPTC) of 0.3-0.8 cm. Group B was composed of 26 women and 3 men (ages 20-63 years) with 3 having FTC, 15 having PTC of 1.2-3.5 cm, and 11 having mPTC of 0.2-0.8 cm. All patients had a history of a WBS after their post-therapeutic 131I dose that showed uptake in the cervical region. After one year, 22 patients from group A had a negative WBS (68.75%) and in group B, 27 patients had a negative WBS (93.1%). The successful rates for the follow-up WBS were significantly different (p=0.017). There were 19 patients in group A in whom the initial Tg was positive. Of these, 14 had a negative follow-up Tg (73.7%). Group B had 9 patients with a positive initial Tg and all of them had a negative follow-up Tg (100%). CONCLUSION The addition of lithium to treatment with 30 mCi 131I in thyroidectomized patients with low-risk DTC improved the efficacy of thyroid RA and therefore might be a better alternative than using higher doses of 131I for remnant ablation in these patients.

Basal serum thyroglobulin measured by a second-generation assay is equivalent to stimulated thyroglobulin in identifying metastases in patients with differentiated thyroid cancer with low or intermediate risk of recurrence.

Background: Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of TSH-stimulated thyroglobulin (s-Tg) instead of basal Tg on T4 therapy (b-Tg). However, these guidelines were established using first-generation Tg assays with a functional sensitivity (FS) of 0.5-1.0 ng/ml. Current more sensitive second-generation Tg assays (Tg2G; FS 0.05-0.10 ng/ml) have shown that low-risk DTC patients with undetectable b-Tg rarely have recurrences. Objectives: This study was undertaken to compare b-Tg using a chemiluminescent Tg2G assay (Tg2GICMA; FS 0.1 ng/ml) with s-Tg in DTC patients with an intermediate risk of recurrence. Methods: We evaluated 168 DTC patients with a low (n = 101) and intermediate (n = 67) risk of recurrence treated by total thyroidectomy (147 also treated with radioiodine), with a mean follow-up of 5 years. Results: b-Tg was undetectable with the Tg2GICMA in 142 of 168 patients. s-Tg was <2 ng/ml in 138 of these 142 patients, and only 3 of these 138 (2%) presented metastases on cervical ultrasound (US). Of the 4 of 142 patients with s-Tg >2 ng/ml, 1 had cervical metastases seen after radioiodine. Furthermore, 26 of 168 patients presented detectable b-Tg with the Tg2GICMA; 17 of these 26 patients also presented s-Tg >2 ng/ml. In 10 of these 17 patients, metastases were detected. Cervical US or b-Tg were positive in 14 of 15 patients with recurrent disease. Globally, the sensitivity and negative predictive value of the Tg2GICMA plus US were 93 and 99%, respectively. Conclusion: b-Tg measured with a Tg2GICMA and cervical US, used together, are equivalent to s-Tg in identifying metastases in patients with DTC with a low or intermediate risk of recurrence.

A Prospective Study Showing an Excellent Response of Patients with Low-Risk Differentiated Thyroid Cancer Who Did Not Undergo Radioiodine Remnant Ablation after Total Thyroidectomy.

Objectives: To prospectively evaluate the outcome of patients with low-risk papillary thyroid carcinoma treated with total thyroidectomy (TT) who did not undergo radioiodine remnant ablation (RRA). Study Design: We prospectively followed up 57 patients; 3 months after TT, thyroglobulin (Tg) assessment and neck ultrasonography (US) were performed while patients were taking L-T4, presenting suppressed TSH. Six months after TT, patients underwent stimulated Tg testing and whole-body scan (WBS) after recombinant TSH (rhTSH). Then, 18 months after TT, the patients were evaluated by neck US and Tg under TSH between 0.5 and 2.0 mIU/ml. Two years after TT, we performed another rhTSH assessment, measuring Tg and making a WBS. The patients were then annually monitored with neck US and Tg measurement under TSH between 0.5 and 2.0 mIU/l for 36-84 months. Results: Neck US of all patients, 3 months after TT, presented no evidence of abnormal residual tissues or metastatic lymph nodes (negative neck US); at this time, the mean Tg level was 0.42 ng/ml. Six months after surgery, after rhTSH, the mean thyroid bed uptake was 1.82%, and Tg levels ranged from 0.10 to 22.30 ng/ml (mean, 2.89 ng/ml). The patients were followed up without any sign of recurrence (negative neck US and stable or decreasing Tg levels). During the ongoing follow-up, the Tg trend was stable or decreasing, independently of the initial suppressed or stimulated Tg level, or WBS uptake. Conclusions: In patients with low-risk differentiated thyroid cancer, who were operated by TT and who did not undergo RRA, an excellent response to treatment may be confirmed by annual neck US and Tg trend.

Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer

OBJECTIVES We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. SUBJECTS AND METHODS Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. RESULTS Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. CONCLUSION Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.

Clinical utility of 18F-FDG PET/CT in the follow-up of a large cohort of patients with high-risk differentiated thyroid carcinoma

OBJECTIVE To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. SUBJECTS AND METHODS Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). RESULTS 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. CONCLUSION 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.

Assessment of the Effect of Two Distinct Restricted Iodine Diet Durations on Urinary Iodine Levels (Collected over 24 h or as a Single-Spot Urinary Sample) and Na+/I- Symporter Expression

Introduction: A restricted iodine diet (RID) may be recommended for depletion of the whole-body iodine pool in patients with differentiated thyroid cancer referred for radioiodine treatment or a whole-body scan. Evaluation of the iodine pool is possible through urinary iodide (UI) measurements, which can be collected in 24-hour (24U) or spot urinary (sU) samples. However, the minimum period required for an RID to lower the iodine pool, the measurement of iodine in sU samples as a iodine pool marker, and the influence of the iodine pool on Na+/I- symporter (NIS) expression are debatable in the literature. Objectives: To compare the effects of 15- and 30-day RID on UI measurements in 24U and sU samples and the impact of RID on NIS expression. Methods: Thyroidectomized patients went on a 15- or 30-day RID and collected 24U and sU samples before and after the RID. Twenty healthy individuals were evaluated for mRNA NIS expression before and after the RID. Results: Of 306 patients, only 125 properly complied with both the RID and 24U collection. We observed a correlation between sU and 24U UI before the RID (n = 306, ρ = 0.47, p < 0.001), after a 15-day RID (n = 79, ρ = 0.49, p < 0.001), and after a 30-day RID (n = 46, ρ = 0.73, p < 0.001). There was a significant decrease in UI after the RID. The median UI measurement was 275 μg/l at baseline and 99 and 80 μg/l after a 15- and 30-day RID, respectively. There was a significant increase in NIS expression after a 15-day RID. Conclusions: A 15-day RID is sufficient to deplete the iodine pool. sU can replace 24U UI as a marker for assessing the iodine pool. NIS expression was increased after a 15-day RID.

Bethesda Classification and Cytohistological Correlation of Thyroid Nodules in a Brazilian Thyroid Disease Center

Background: The Bethesda System has been used to classify thyroid cytology in 6 categories besides presenting malignancy rates and respective approaches. Reference centers have validated its use by comparing its proposed malignancy rates with those in in their populations. However, to the best of our knowledge, there has been no corresponding study in Brazil. Objectives: To evaluate the performance of the Bethesda classification in a Brazilian thyroid reference center and correlate the results with cytohistological reports in patients referred to surgery. Methods: Data records from 980 fine-needle aspiration (FNA) results were retrospectively analyzed, and, in patients who underwent surgery, the results were correlated with the cytohistological findings. Results: 980 FNAs and 585 patients were evaluated. The incidence of each cytological category was: 11% nondiagnostic (ND), 59.6% benign, 7.1% (atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 8.5% follicular neoplasm or suspicious for follicular neoplasm (FN/SFN), 5.1% suspicious for malignancy (SM), and 8.3% malignant. The surgery rate was 41.8% (245/585). The malignancy rate in each category was: 6% benign, 12% AUS/FLUS, 20.8% FN/SFN, 72.5% SM, and 97.3% malignant. For ND nodules, the malignancy rate was 25.7% (66.6% multifocal and papillary microcarcinomas), a higher rate than in the literature. In this category, surgery was performed in multinodular goiters presenting with another nodule > 3.0 cm and/or with an FN/SFN, SM, or malignant cytological result. Conclusion: The Bethesda System can be applied to the Brazilian population, since the frequency and malignancy rates of each category were similar to those described by its classification. It is noteworthy that a higher risk of malignancy was observed in the ND cytological category.