Negative DxWBS Research Articles

The efficacy and safety of sequential use of anlotinib and 131I for locally advanced or metastatic differentiated thyroid cancer: A single-arm phase II clinical trial.

e18102 Background: Locally advanced or metastatic differentiated thyroid cancer (DTC) commonly responds poorly to radioiodine (131I) treatment alone. Tyrosine kinase inhibitors, however, have exerted promising antitumor activity in multiple advanced solid tumors. This study aimed to investigate the efficacy and safety of sequential use of anlotinib and 131I for the treatment of locally advanced or metastatic DTC. Methods: This is a single-arm phase II open-label clinical trail. The key eligibility criteria included locally advanced or metastatic 131I-avid DTC, ECOG PS of 0-1, and at least one measurable lesion. Previous tyrosine kinase inhibitor was not allowed. Patients initially received anlotinib (12 mg QD, 2 weeks on/1 week off ) for 4 cycles. At the beginning of 13th week when levothyroxine had been discontinued for 4 weeks, diagnostic 131I whole body scan (Dx-WBS) was performed, and those with 131I-avid lesions were immediately identified to undergo 131I treatment. The primary endpoint was objective response rate (ORR) . The secondary endpoints included disease control rate (DCR), biochemical response rate (BRR), time-to-response (TTR), progression-free survival (PFS), and safety. Results: From June 2021 to December 2022, a total of 16 patients with locally advanced or metastatic DTC were included. At the data cut off, 8 patients (4 males and 4 females) were withdrawn from the trial due to negative Dx-WBS, and the remaining 8 patients were subsequently treated with 131I. Six patients who had completed at least one cycle of sequential treatment were eligible for data analysis. Partial response and stable disease were found in 2 (33.33%) and 3 (50%) patients, respectively. An ORR of 33.33% [95% CI, 4.33-77.72], a DCR of 83.33% [95% CI, 35.88-99.58], a BRR of 100% [95% CI, 54.07-100.00], and a TTR of 6.34 months [95% CI, 5.85-NE] were achieved. Median PFS was not reached. Grade 3 adverse events occurred in 2 (33.33%) of the 6 subjects, including pain owing to skeletal metastasis in one patient and drug-related hypertention in the other. Conclusions: This study firstly demonstrates the favorable efficacy and safety of sequential therapy with tyrosine kinase inhibitor and 131I, suggesting anlotinib as a adjuvant option for 131I treatment of locally advanced or metastatic DTC. Randomized controlled studies on sequential therapy versus 131I treatment are warranted. Clinical trial information: ChiCTR2100045178 .

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.

AntiThyroglobulin Antibody as a Prognostic Factor to Evaluate the Recurrence and Metastases of Differentiated Thyroid Carcinoma following Radioactive Iodine Ablation

Objectives: Patients with Differentiated Thyroid Carcinoma (DTC) are usually treated with thyroidectomy followed by radioactive iodine ablation (RAIA). After treatment, during their follow up period, serum thyroglobulin (Tg) estimation and diagnostic whole body 131I scan (DxWBS) are established modalities to observe recurrence. The aim of this study was to evaluate the clinical significance of TgAb levels for possible use as a prognostic factor of recurrence and metastases of disease. Patients &amp; Methods: An observational Cohort study was conducted in total 48 diagnosed DTC patients who underwent total thyroidectomy followed by RAIA during July, 2016 to June, 2017 at National Institute of Nuclear Medicine &amp; Allied Sciences (NINMAS). Among them, 24 patients with high TgAb level (&gt;40 IU/ml) were considered as group I and 24 DTC patients with low TgAb level (&lt;40 IU/ml) was considered as group-II. Detail history, clinical examination, Tg &amp; anti TgAb levels were assessed and DxWBS were done in all patients. Fine needle aspiration cytology (FNAC) of enlarged lymphnodes and 18Fluorine- fluorodeoxyglucose positron emission tomography-Computed Tomography (18F-FDG PET-CT) were done in patients with negative DxWBS but having high anti TgAb. Demographic and clinicopathological characteristics were compared between two groups and recurrence and metastases were observed. Statistical analysis was done. Results: Among 24 patients of Group-I, 6 patients showed either metastases or recurrences and no patient of group-II showed metastasis or recurrence. The difference was statically significant (p&lt;0.05) between two groups. Relative risk (RR) was found 2.33 in group-I in comparison to group-II, suggesting the patients at higher risk of metastases or recurrence in group-I than group-II who had high anti TgAb. Conclusion: Among DTC with high TgAb patients, papillary carcinoma was more common. Recurrence and metastases were evaluated in 6(25%) patients who had high antiTgAb level and 0% with low anti TgAb levels. This may be concluded that, high TgAb levels in patients with DTC could be considered as a marker to evaluate recurrence and metastases after RAIA. Patients of DTC with high TgAb are at risk of recurrence and metastases during follow up period as the RR was found 2.33. Bangladesh J. Nuclear Med. 23(1&amp;2): 9-14, 2020

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

Outcome of radioiodine therapy in patients with papillary thyroid carcinoma concurrent with Hashimoto′s thyroiditis

Objective To evaluate the impact of low-dose 131I therapy and high-dose 131I therapy on the clinical outcome in PTC patients coexisting with Hashimoto′s thyroiditis (HT). Methods A total of 140 non-distant metastatic PTC patients (16 males, 124 females, age range: 16-66 years) from July 2010 to December 2014 were enrolled in this retrospective study. Patients concurrent with HT (n=84, group A) were divided into low-dose group (1 110 MBq, n=56, group A1) and high-dose group (5 550 MBq, n=28, group A2) according to 131I ablation dose. Patients without HT (n=56) were enrolled as control group (group B), and received 1 110 MBq of 131I. The thyroid remnant ablation outcome was evaluated according to 131I diagnostic whole-body scan (Dx-WBS), neck ultrasonography (US), serum Tg and TgAb level 6-8 months after 131I ablation therapy. The successful ablation rates were compared by χ2 test. Kruskal-Wallis rank sum test was also used. Results There were no significant differences among the 3 groups in terms of both clinicopathological features and postoperative remnant thyroid (H: 0.203-2.944, χ2: 0.271-0.970, all P>0.05). When negative Dx-WBS and US were deemed as successful ablation criterion, complete ablation rate was found significantly more in group B (94.6%, 53/56) than that in group A1 (82.1%, 46/56; χ2=4.264, P 0.05). When combining negative sTg (sTg 0.05), and no difference was observed between group A2 (12/15) and group A1 (χ2=1.320, P>0.05). Conclusion Non-distant metastatic PTC patients coexisting with HT has undesirable 131I ablation outcome compared with those without HT, increasing 131I dose is unhelpful to enhance efficiency of remnant ablation for PTC patients with HT. Key words: Thyroid neoplasms; Hashimoto disease; Radiotherapy; Iodine radioisotopes; Treatment outcome

Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in Korean Patients With Differentiated Thyroid Carcinoma: The First Report in Nonwestern Countries.

The aim of this study was to confirm the equivalent efficacy of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) as used in the preparation for low-dose and high-dose radioactive iodine (RAI) ablation in Korean patients with differentiated thyroid carcinoma. This retrospective study was designed to compare the efficacy of rhTSH and THW when used before ablation with low-dose (30 mCi) and high-dose (100 mCi) RAI, respectively. The study group included 570 patients with DTC with tumors staged T1 to T3, N0 to N1, and M0. Before RAI ablation, 190 patients used rhTSH and 380 patients matched by age, sex, T-stage, and N-stage used THW. The success of ablation was evaluated in each group based on 4 criteria: (1) stimulated thyroglobulin (sTg) <2 ng/mL, (2) sTg<2 ng/mL and negative diagnostic whole-body scan (DxWBS), (3) sTg<1 ng/mL, and (4) sTg<1 ng/mL and negative DxWBS. When both sTg<2 ng/mL and negative DxWBS were selected as criteria for success in patients treated with low-dose RAI, the success rates were 80.5% and 77.0% with rhTSH and THW, respectively (95% confidence interval, 5.9-12.8). Using both sTg<1 ng/mL and negative DxWBS as criteria, success rates were 78.2% and 71.8% with rhTSH and THW, respectively (95% confidence interval, 3.6-16.2). Using any criteria for success, low-dose RAI ablation with rhTSH was as effective as THW. Similar results were found for high-dose RAI ablation in patients using either rhTSH or THW. Low-dose and high-dose RAI ablation were equally effective using either rhTSH or THW before ablation in Korean patients with DTC, respectively.

The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer.

Surgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. DTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6-9 months after RAI. There were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11±12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. Postoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients.

Low-dose radioiodine ablation in differentiated thyroid cancer with macroscopic extrathyroidal extension and low level of preablative-stimulated thyroglobulin.

High-dose radioactive iodine (RAI) is recommended for patients with nonmetastatic differentiated thyroid cancer with macroscopic extrathyroidal extension (MAEE). It is unclear whether these patients can be treated with low-dose RAI when preablative-stimulated thyroglobulin (ps-Tg) is low. This randomized study aims to evaluate the clinical outcome and ablative efficacy of low-dose radioiodine in patients with MAEE but with low ps-Tg level. Differentiated thyroid cancer patients with complete thyroidal resection, MAEE, any N stage, ps-Tg less than or equal to 5 ng/ml when thyroglobulin antibodies are less than or equal to 46 IU/ml, and no evidence of distant metastasis were included in the study. Patients were randomly allocated to receive low-dose (1110 MBq) or high-dose RAI (3700 MBq). Follow-up was generally performed 6 months after ablation. Successful ablation was identified as (i) stimulated thyroglobulin 1.0 ng/ml or less when thyroglobulin antibodies 46 IU/ml or less; (ii) negative Dx-WBS; and (iii) negative neck ultrasonography. Clinical recurrence was defined as the reappearance of disease confirmed by cytology or pathology. A total of 102 patients were analyzed: 51 in the low-dose group and 51 in the high-dose group. There was no significant difference in clinicopathological characters between the two groups. No patient had clinical recurrences during the mean 6.8 months of follow-up. Ablation was successful in 43 of 51 (84.3%) patients in the low-dose group and in 44 of 51 (86.27%) patients in the high-dose group, and thus no significant difference was noted (P=0.7798). Ablation with low-dose RAI has been proven to be noninferior to high-dose RAI in nonmetastatic patients with MAEE when ps-Tg level is less than 5 ng/ml.

The Value of Diagnostic Whole-Body Scanning and Serum Thyroglobulin in the Presence of Elevated Serum Thyrotropin During Follow-Up of Anti-Thyroglobulin Antibody–Positive Patients with Differentiated Thyroid Carcinoma Who Appeared to Be Free of Disease After Total Thyroidectomy and Radioactive Iodine Ablation

In the presence of anti-thyroglobulin antibodies (TgAb), serum thyroglobulin (Tg) might be underestimated. Therefore, the American Thyroid Association does not recommend serum Tg after thyroid hormone withdrawal or recombinant human thyrotropin administration (stimulated Tg) and diagnostic whole-body scanning (DxWBS) in TgAb-positive patients who have serum Tg values while on thyroxine (Tg-on-T4) of <1 ng/mL. The objective of this study was to determine, in patients with differentiated thyroid cancer (DTC) who appeared to be free of disease after surgery and ablative treatment, but who had positive serum TgAb, the value of performing DxWBS and obtaining serum Tg under stimulated Tg conditions. There were 121 women and 15 men in the study. By selection criteria, all of them had total thyroidectomy with apparent complete tumor resection, remnant ablation with (131)I (1.1-5.5 GBq), and a post-(131)I therapy WBS that were negative for ectopic (131)I uptake. On assessment 8-12 months after (131)I ablation, their clinical exam needed to be normal, their Tg-on-T4 needed to be <1 ng/mL, and the test for TgAb needed to be positive. Stimulated Tg, neck ultrasound (US), and DxWBS were obtained from all patients. Patients with stimulated Tg >1 ng/mL without disease on US and DxWBS were evaluated by other imaging methods. In 10 (7.3%) patients, stimulated Tg was >1 ng/mL. The DxWBS revealed metastases in two of these patients, and other imaging methods showed disease in three others. Stimulated Tg was <1 ng/mL in 126 patients. DxWBS revealed metastases in three of these patients, and US detected lymph node metastases in four with a negative DxWBS. Tg stimulation combined with DxWBS revealed evidence for disease in 13 (9.5%) patients. When excluding patients with a positive US, DxWBS revealed metastases in four patients, and stimulated Tg of >1 ng/mL led to detection of persistent disease by other imaging methods in two more patients. Performing stimulated Tg and DxWBS at the same time seems to be useful after initial therapy in DTC patients with TgAb who do not otherwise appear to have persistent disease, even when US is negative.

The Role of Routine Diagnostic Radioiodine Whole-Body Scintigraphy in Patients with High-Risk Differentiated Thyroid Cancer

Follow-up diagnostic radioiodine whole-body scintigraphy (DxWBS) is still advised for high-risk patients with differentiated thyroid cancer. The aim of this study was to evaluate the additional value of DxWBS to stimulated thyroglobulin measurement in high-risk patients. The results of DxWBS and thyroglobulin measurements performed 6-12 mo after surgery and radioiodine thyroid remnant ablation in patients with differentiated thyroid cancer were retrospectively evaluated for 112 patients with high-risk features for recurrence (R3/T4 and N1). One patient had an undetectable thyroglobulin level, with DxWBS results suggestive of cervical recurrence. DxWBS was found to be false-positive. Of the patients with detectable thyroglobulin levels, the DxWBS results were negative in 65 and positive in only 8. The 6 patients positive for thyroglobulin antibody had negative DxWBS results. The remaining patients had an undetectable thyroglobulin level and negative DxWBS results. Because undetectable stimulated thyroglobulin levels have a negative predictive value of 100%, DxWBS offers no information additional to recombinant human thyroid-stimulating hormone-stimulated thyroglobulin measurements in patients with high-risk differentiated thyroid cancer.

Seguimento de pacientes de alto risco com carcinoma diferenciado de tireóide sem doença persistente após a terapia inicial

This study evaluated the follow-up of high-risk patients with thyroid cancer after initial therapy. A total of 125 high-risk patients (tumor >4 cm and/or extrathyroid invasion and/or lymph node metastases, and age >45 years), with complete resection of the tumor, were selected. All patients underwent total thyroidectomy and ablation with (131)I[3.7-5.5 GBq (100-150 mCi)]. Eighteen patients (14.8%) presenting metastases on post-dose whole-body scan (RxWBS) were excluded. The negative predictive value of stimulated Tg < or =1 ng/ml in combination with neck US during first assessment (612 mo. after ablative therapy) was 96.2% for the absence of recurrence up to 5 years. This value increased to 98.7% when adding WBS performed with 185 MBq (5 mCi) (131)I (DxWBS). The positive predictive value (PPV) of stimulated Tg >1 ng/ml was 52% for the detection of the presence of metastases up to 5 years; however, considering only patients with initially negative DxWBS and US, the PPV was 19% (9% if Tg of 110 ng/ml vs. 40% if Tg >10 ng/ml). Tg levels decreased spontaneously in patients with stimulated Tg >1 ng/ml during first assessment, negative US and DxWBS, and no recurrence during follow-up, with Tg being undetectable in half these patients at the end of 5 years. Twenty patients presented uptake in the thyroid bed upon DxWBS during the first year after ablative therapy, with stimulated Tg and US being negative, and were not treated with 131I; these patients did not relapse and no uptake on DxWBS was observed in 60% after 5 years. Recurrence after 5 years was only 1.3% in patients without apparent disease (negative US and DxWBS) and stimulated Tg <1 ng/ml. An algorithm for the follow-up of high-risk patients after initial therapy is presented in this study.

Use of the Recombinant Human TSH Stimulated Thyroglobulin Level and Diagnostic Whole Body Scan in Children with Differentiated Thyroid Carcinoma

The recombinant human thyrotropin (TSH) (rhTSH) stimulated thyroglobulin (Tg) level is a useful tumor marker for disease surveillance in adults with differentiated thyroid carcinoma (DTC). We report our institution's experience using rhTSH in children. Seven children with DTC on thyroid hormone suppressive therapy after total thyroidectomy and radioablation received rhTSH (0.9 mg i.m.) on day 1 and 2. TSH rose to 224 +/- 93 mIU/l on day 2 and 13 +/- 5 mIU/l on day 5. Serum Tg level and diagnostic whole body radioiodine scan (DxWBS) were assessed on day 5. Five children were disease free: all had negative DxWBS; two had Tg < or = 2.1 ng/ml; two had anti-Tg antibodies; and one had no Tg measured. Two children had recurrent disease: one had a negative DxWBS and Tg of 15 ng/ml; and one had a positive DxWBS and no Tg measured. There were no adverse effects from rhTSH. These results suggest that rhTSH can be safely used for disease surveillance in children with DTC.

Long-term course and predictive factors of elevated serum thyroglobulin and negative diagnostic radioiodine whole body scan in differentiated thyroid cancer

Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and negative diagnostic radioactive iodine (RAI) whole body scan (DxWBS). The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to determine the predictive factors for the development of high Tg and negative DxWBS (Tg+/scan-) and to study the long-term course of the disease in patients with this condition. We, retrospectively, reviewed the medical records of a cohort of 105 non-selected DTC patients (26 males and 79 females; median age 37.7 yr, range 7-72). None of these patients had positive Tg antibodies or distant metastases. All Tg levels were obtained off thyroid hormone therapy. At the first follow-up visit after RAI ablation (13 +/- 7.6 months), patients were classified into those with low Tg (<2 ng/ml off L-T4) and negative DxWBS (control group) and those with high Tg ( > or = 22 ng/ ml off L-T4) and negative DxWBS (Tg+/scan- group). Using univariate and multivariate logistic regression analyses, we evaluated a number of parameters (see results) for their association with the development of Tg+/scan-. In addition, the long-term course of the disease in Tg+/scan- group was analyzed. In univariate analysis, the following factors were found to be significantly associated with Tg+/scan-: perithyroidal tumor extension (p=0.025), soft tissue invasion (p=0.001), cervical lymph node metastases (p=0.014) and Tg level before RAI ablation (p=0.015). In multivariate analysis, only soft tissue invasion remained significantly associated with Tg+/scan- [p 0.001, odds ratio, 15.6 (95% Cl, 2.96-82.06)]. Age, sex, duration of goiter before surgery, pressure symptoms, tumor size, tumor multifocality, lymph nodedissection at initial surgery, tumor-node-metastasis (TNM) stage, and RAI ablative dose were not associated with Tg+/ scan-. In 53 patients with Tg+/scan-, 42 cases were followed without any therapeutic intervention; over a median follow-up of 71.6 months (range, 13-144.7), 31 cases had a spontaneous remission and 11 cases continued to have a persistent disease (Tg > or = 2 ng/ml, negative DxWBS, and no palpable disease or distant metastases); Tg declined from 9.32 +/- 9.91 ng/ml at first visit after RAI ablation to 1.59 +/- 5.39 ng/ml at last visit (p<0.0001). In the other 11 cases of Tg+/scan- group, one or more therapeutic interventions (RAI, surgery, or external radiotherapy) were undertaken. Over a median follow-up of 98.4 months (range, 6-147), Tg decreased from 110.2 +/- 147.5 to 23.5 +/- 41.2 ng/ml (p 0.026); 4 cases achieved remission, 5 cases continued to have persistent disease, and 2 cases had progression of their disease, which led to their death. Soft tissue invasion on original surgery strongly predicts the development of Tg+/scan- in DTC patients. The long-term course of the disease is mostly favorable especially when the Tg level is only modestly elevated.

Effects of therapeutic doses of 131I in thyroid papillary carcinoma patients with elevated thyroglobulin level and negative 131I whole-body scan: comparative study.

Previous studies have shown a high rate of visualization of uptake and a decrease in serum thyroglobulin (Tg) after therapeutic doses of 131I in well-differentiated thyroid cancer patients with elevated thyroglobulinaemia but negative diagnostic 131I whole-body scan (DxWBS), but its therapeutic effect remains controversial. We evaluate the effect of therapeutic doses of 131I in patients with elevated thyroglobulin level but negative DxWBS. Among papillary thyroid carcinoma patients who underwent total or near-total thyroidectomy and remnant ablation with radioiodine during 1996 to 2000 in our hospital, the patients who showed elevated serum Tg levels and no abnormal uptake in DxWBS were selected. The selection for treatment or no treatment was decided according to the preference of the patients, considering side-effects of therapeutic doses of 131I, and the patients were thereafter studied retrospectively. Sixty papillary thyroid carcinoma patients with elevated thyroglobulinaemia but negative DxWBS were included. Twenty-eight patients were treated, and 32 were untreated. We compared serum Tg levels measured at less than 3 months before the administration of therapeutic doses of 131I or DxWBS with the levels at 6-12 months after administration between two groups. Comparable data on changes in serum Tg levels during TSH suppression (Tg-on) and those in hypothyroid phase (Tg-off) were available in 25 and 49 patients, respectively. Percentage decreases in both Tg-on and Tg-off levels of the treated group [41.2 (10.1-94.1)% and 37.0 (-176.6-88.4)%, respectively] were significantly higher than those of the untreated group [-43.6 (-180.1-7.3)% and -66.6 (-10644.2-39.1)%, respectively] (P < 0.001). The treated patients were followed-up for 23.8 +/- 19.6 months after the administration of therapeutic doses of 131I. In four cases, serum Tg levels converted to negative (< 1.0 ng/ml) both on and off T4 15-22 months after the administration of therapeutic doses of 131I, and negative serum Tg levels persisted for 24-70 months. However, negative conversion of elevated serum Tg levels was not observed in any of the untreated group. Post-treatment WBS revealed pathologic uptake in 12 of 28 cases (42.9%). This study revealed that the administration of therapeutic doses of 131I has a therapeutic effect, at least for palliation in short-term observation, considering the serum Tg level as an index of tumour burden, and that it can disclose previously undiagnosed lesion in some patients with differentiated thyroid cancer who show elevated thyroglobulin level but negative diagnostic 131I whole-body scan.

Is the serum thyroglobulin response to recombinant human thyrotropin sufficient, by itself, to monitor for residual thyroid carcinoma?

The serum thyroglobulin (Tg) response to elevated TSH is one of the most sensitive indexes of residual thyroid carcinoma. We have explored the possibility that this test alone would be sufficient to detect residual thyroid carcinoma in thyroid cancer patients after total thyroidectomy and radioiodine remnant ablation. We used recombinant human TSH (rhTSH) to elevate serum TSH, rather than withdraw the patients from thyroid hormone. Routine evaluations, including diagnostic radioiodine whole body scans (DxWBS) and serum Tg, were performed on 366 patients after preparation by rhTSH, over a 2-yr interval. A retrospective analysis of the data from these patients revealed that 76% of those whose stimulated Tg rose to more than 2 microg/liter had evidence for residual thyroid carcinoma, whereas the same was true for only 13% of those whose stimulated Tg was 2 microg/liter or less. Using risk group stratification, we analyzed outcomes in a low risk subset (which excluded patients with elevated Tg levels on suppression, known metastatic disease, and clinical or histological evidence of aggressive disease). In this low risk group, we found that a stimulated Tg of 2 microg/liter or less had a 91.7% negative predictive value. No low risk patient who had had a prior negative DxWBS and a stimulated Tg of 2 microg/liter or less had any evidence of residual thyroid carcinoma. We conclude that the stimulated Tg alone is not sufficient by itself to screen unselected patients, but that it may be sufficient in low risk patients, especially those who have had a prior negative DxWBS.

Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma.

Clinical recurrences of differentiated thyroid carcinoma occur in 20% of patients after thyroid surgery. We performed a retrospective analysis of a cohort of patients undergoing routine follow-up testing to detect recurrent thyroid carcinoma over a 2-yr period. One group was prepared for testing by thyroid hormone withdrawal (THW), and the other group remained on thyroid hormone and received injections of recombinant human TSH (rhTSH) before diagnostic whole-body radioiodine scanning (DxWBS). We hypothesized that no differences in the ability to detect residual disease would exist between these 2 groups. Two hundred and eighty-nine patients were examined by both DxWBS and by measurement of the serum thyroglobulin (Tg) response to elevated TSH levels. THW was used for 161 patients, and rhTSH preparation was used for 128 patients. Based on all available testing results, we categorized patients as having metastatic disease, thyroid bed uptake only, or no evidence of disease. We examined the sensitivity, specificity, positive and negative predictive values of the DxWBS, and the stimulated Tg after preparation by THW or rhTSH. Patients with thyroid bed were not considered in accuracy testing. The sensitivity and specificity of the 2 tests were comparable between groups. No significant differences were present in the positive or negative predictive values between groups. The highest negative predictive value (97%) was in patients who had both a negative DxWBS and low stimulated Tg levels after rhTSH. In summary, we were unable to demonstrate a difference in the diagnostic accuracy of DxWBS and/or Tg between patients prepared by either THW or rhTSH. We conclude that preparing patients by rhTSH is diagnostically equivalent to preparing them by THW.