Semi-quantitative assessment of salivary gland function in patients with differentiated thyroid carcinoma after radioiodine-131 treatment

Sialadenitis and xerostomia are well-known side effects of high-dose radioactive iodine ((131)Iota) treatment in patients with differentiated thyroid carcinoma (DTC). This study was undertaken to determine salivary gland function semi-quantitatively in patients with DTC given (131)I for the treatment of the thyroid remnant and/or metastases. Thirty-six patients, 11 males and 25 females, mean age 53.5 years, range 22-73 years, were studied. Scintigraphy of the salivary glands was performed with (99m)Tc-pertechnetate and the salivary excretion fraction (SEF) of the parotid and the submandibular glands was calculated as a measure of their function. Measurements were performed before (131)I treatment as a baseline study, and three weeks and three months later. The patients were clinically evaluated by a standardized subjective questionnaire. Results were as follows: Mean SEF at three weeks and three months after (131)I treatment was reduced as compared to baseline measurements. The total mean baseline measurements, those of three weeks and those of three months later were: 54.9%, 47.2% and 46% respectively; P<0.05 for both measurements (Table 1). The SEF decrease of the parotid glands was greater than that of the submandibular glands (P<0.05 as compared for both salivary glands before and three weeks and three months after (131)I treatment). This confirmed the higher radiosensitivity of the parotid glands as compared to the submandibular glands. In 12 patients (33%) there was no significant decrease of SEF in the salivary glands after (131)I treatment. The relation between the decrease of SEF after three weeks and after three months and the dose of (131)I administered, was for the right and left submandibular glands significant (P=0.016 and P=0.002), while for the parotid glands it was insignificant (P=0.22 and P=0.27 respectively) (Table 4). Reduction of SEF in the parotid glands three months after (131)I treatment was greater than after three weeks. This difference, as regards the submandibular glands, was not significant. Our results show that high dose (131)I treatment in DTC patients induces a significant effect on salivary gland function, which is dose-related in the submandibular glands, and more prominent in the parotid glands.     

Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma

In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post-therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung.     

Time course of thyroglobulin autoantibodies in patients with differentiated thyroid carcinoma after radioiodine therapy

The time course of thyroglobulin (Tg) was monitored in patients with differentiated thyroid carcinoma after ablative therapy (thyroidectomy + 131I-treatment) with particular respect to endogeneous antibodies (Tg-ABs). In 232 patients (196 without Tg-ABs, 36 with Tg-ABs at the time of treatment) a sensitivity of 88% (accuracy, 93%) was found at the first follow up examination. Twelve months later, 11 of the 36 patients did not present Tg-ABs, therefore, the sensitivity increased to 91% (accuracy, 94%) at that time. It is expected that the determination of Tg can also be employed in patients presenting ABs initially.     

Cytokinesis-block micronucleus test in patients undergoing radioiodine therapy for differentiated thyroid carcinoma

Cytokinesis-blocked micronucleus assay (MNT) was applied in the peripheral blood lymphocytes of patients undergoing radioiodine-131 ((131)I) therapy for differentiated thyroid carcinoma (DTC) after thyroidectomy to assess the genotoxic risk of this therapy. The amount of administered (131)I activity varied from 3,330 to 4,030 MBq. Blood samples were taken immediately before (131)I administration and one month later, along with routine blood tests. Twenty-six patients underwent radioiodine ablation (RIA) or radioiodine therapy (RIT) after radical thyroidectomy. The aim of this therapy was to ablate residual thyroid tissue, to treat lymph node metastases and/or distant lung metastases. The amount of orally administered activity of (131)I ranged between 3,330 and 4,030 MBq according to the kind of therapy (RIA or RIT). In five patients the cytogenetic analysis was performed immediately before and one month after the second therapy which was given to them 6 months to 1 year after the first. Three patients were male and 23 female. The age of the patients ranged between 23 and 76 years (mean age: 48.6 years). Results show that after radioiodine therapy there is a significant increase in the frequency of micronuclei. Comparing the average frequency of micronuclei in the patients studied before and after (131)I, a more than doubling increase was found. Mean values +/- SD of the patients before and after (131)I therapy were 10.72 per thousand +/- 5.84 per thousandand 25.28 per thousand +/- 12.6 per thousand respectively. These findings indicate a genotoxic activity of (131)I therapy estimated after a period of one month.     

Post-surgical ablation of thyroid remnants with high-dose (131)I in patients with differentiated thyroid carcinoma

The aims of this study were to evaluate the efficacy of an empirically determined "fixed" high ablative dose of radioiodine ((131)I) therapy and to determine the utility of ultrasonography (US) in dose determination. A retrospective analysis was performed of 242 thyroid cancer cases treated with "fixed" high-dose (131)I for ablation of thyroid remnants without a pre-ablative (131)I diagnostic scintigraphy or radioiodine uptake study. Treatment doses ranged from 1850 MBq (50 mCi) to 7.4 GBq (200 mCi). The selection of the treatment dose was based on the surgical and pathological findings as well as the remnant thyroid volume calculated by US. A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies. Successful ablation was obtained in 218 of the 242 patients (90%). In 162 of the 218 patients (74.3%), successful ablation was achieved after a single (131)I treatment. The remnant thyroid volume calculated by US was significantly different (P=0.04) between those who were successfully ablated and those who were not. The total (131)I dose needed for successful ablation was significantly higher in males (P=0.003). Patients with higher post-operative thyroglobulin (Tgb) levels and patients with a higher stage of disease required higher doses (P=0.036 and P=0.021 respectively). Serum Tgb levels were under 10 ng.ml(-1) in 220 of the 242 patients (90%) following radioiodine ablation while not receiving L-thyroxine suppression. Nineteen patients (7.8%) showed metastases on post-therapy scan and successful treatment was achieved in 11 of 19 (57.8%). Four of the 19 patients with distant metastases (revealed on post-treatment scan) were found to have been given a treatment dose of less than 200 mCi based on the proposed empirical approach. These results indicate that "fixed" high-dose (131)I treatment is clinically feasible with an acceptable dose underestimation rate, and the utilization of US in the determination of the thyroid remnant volume provides more accurate and reproducible results.     

Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy

OBJECTIVES: This was a retrospective study to assess the efficacy and morbidity of high activity I therapy in patients with advanced differentiated thyroid carcinoma. METHODS: From 1975 to 2003, 38 patients with locally advanced or metastatic differentiated thyroid cancer (16 follicular, 20 papillary, one Hurthle cell, one insular) were treated with high activity radioiodine therapy (9 GBq) as the cancers had previously not responded to standard activities (5.5 GBq). RESULTS: Cumulative total activities received ranged from 11.8 to 84.5 GBq (mean 29.4 GBq per patient). Staging at presentation showed pT4 and/or M1 disease in 27/38 of patients (71.1%). Moderate (grade 2) and poorly differentiated (grade 3) tumours were present in a total of 9/38 patients (23.7%). Outcomes were evaluated according to the results of I whole-body scans, serum thyroglobulin, radiological assessments and physical examination. Neither [18F]flurodeoxyglucose positron emission tomography (F-FDG PET) nor 99mTc sestamibi were available during this study. The mean duration of follow-up was 83 months. A complete response was observed in 7/38 patients (18.4%), progressive disease in 27/38 (71.1%) and stable disease in 4/38 (10.5%). The mean survival from initiation of high activity treatment was 36.6 months. For patients with lung disease the mean survival was 45 months, neck disease 38.9 months, bone disease 35 months and multiple sites was 30.9 months. Twelve patients died during follow-up (10 due to thyroid carcinoma). After high activity treatment, 9.7% of patients suffered grade 3 and 3.2% suffered grade 4 WHO haematological toxicity. Significant salivary gland morbidity was observed (30% dry mouth, 27% salivary swelling). CONCLUSIONS: Repeated treatment with high activity (9 GBq) I in patients with advanced differentiated thyroid carcinoma appears to be of no apparent benefit and may lead to late morbidity.     

131I治疗分化型甲状腺癌对甲状旁腺功能的短期影响

目的 探讨131I清除术后残留甲状腺组织(简称清甲)治疗对DTC患者在治疗后短期内甲状旁腺功能的影响.方法 DTC患者共73例,其中男15例,女58例,年龄20～70( 44.59±12.89)岁.分别于131I清甲治疗前1天及治疗后第5天检测患者血Ca2+及PTH水平,比较131I清甲前后患者的血清PTH变化.以性别、年龄及术后超声示甲状腺残留组织(简称残甲)情况分组,分析影响治疗后血清PTH下降的因素.使用SAS 8.0软件对治疗前后计量数据等行配对t检验及方差分析,对年龄组与残甲组间数据行x2检验.结果 131I清甲治疗前后所有患者血钙均在正常范围,均值分别为(2.24±0.93)和(2.23±0.84) mmol/L,差异无统计学意义(t=1.81,P＞0.05);治疗后DTC患者血清PTH为(27.19±11.58) ng/L,明显低于治疗前的(37.33±17.71)ng/L(t=6.76,P＜0.01),其中79.45％ (58/73)的患者PTH较治疗前下降,10.95％ (8/73) PTH值低于正常;但均未出现低钙血症.治疗前后不同性别组间血清PTH差异无统计学意义(t=1.06和1.83,P均＞0.05),但发生PTH降低例数比较有统计学意义(x2=4.37,P=0.036).不同年龄组及不同残甲组治疗前后血清PTH的变化差异均无统计学意义(F=0.58、0.61,0.46、0.76,P均＞0.05).结论 131I治疗可导致DTC患者短期内PTH水平降低,女性更为敏感,但一般不会引发低钙血症.这种变化与年龄及残甲组织多少无关.     

非高危分化型甲状腺癌低剂量和高剂量131I清甲疗效的分析

目的 研究应用低剂量（1.11 GBq）和高剂量（3.70 GBq）放射性131I清除非高危分化型甲状腺癌（DTC）术后残留甲状腺组织的疗效。 方法 回顾性分析行131I清甲治疗的63例非高危DTC患者的临床资料,采用Binary Logistic回归分析年龄、首次手术距清甲的时间间隔、甲状腺24 h摄碘率、血清TSH水平和清甲剂量对清甲疗效的影响;27例患者给予低剂量、36例患者给予高剂量的131I清甲治疗,采用Pearsonχ2检验分析低剂量和高剂量131I清甲疗效的差异,P < 0.05表示差异有统计学意义。 结果 63例非高危DTC患者中,清甲成功者46例（73.02%,46/63）、未成功者17例（26.98%,17/63）;Binary Logistic回归分析显示,131I清甲剂量是清甲成功与否的主要影响因素（Wald=6.42,P=0.011）;27例给予低剂量131I清甲患者中有15例清甲成功,36例给予高剂量131I清甲者中31例清甲成功,Pearsonχ2检验结果表明,高剂量131I清甲成功率（86.11%,31/36）明显高于低剂量（55.56%,15/27）（χ2=7.311,P=0.007）。 结论 在临床实践中,当残余甲状腺组织较少时,对于非高危DTC患者可考虑采用高剂量131I清甲治疗,提高一次清甲成功率。     

Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single-centre study of 54 patients

We sought to evaluate the efficacy, biochemical effects, safety and outcome of recombinant human thyroid-stimulating hormone (rhTSH) as an adjunct to radioiodine treatment of advanced differentiated thyroid carcinoma (DTC). We also sought to determine whether rhTSH is useful as an adjunct to radioiodine treatment following isotretinoin re-differentiation therapy of DTC metastases that have lost function. Therefore, in 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of (131)I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T(4)) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients with non-functional metastases at baseline. Although within-patient comparison of early outcome after both modalities is limited by a significantly greater median number of courses and a greater median cumulative activity of radioiodine given under withdrawal, response to rhTSH-aided and withdrawal-aided treatment was similar in 23 (52%) of 44 evaluable patients, superior with rhTSH in 12 (27%) and superior with withdrawal in seven (16%). In two patients, a superior response was obtained after isotretinoin pretreatment and rhTSH and attributed to re-differentiation therapy. In conclusion, our study provides preliminary evidence that rhTSH safely and effectively aids radioiodine treatment of advanced DTC, and does so to an at least equivalent degree as does T(4) withdrawal.     

Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment

PURPOSE: Sialadenitis is a well-recognized adverse effect of high-dose radioactive iodine treatment. This study was undertaken to determine whether Tc-99m pertechnetate salivary gland scintigraphy may be used for objective assessment of salivary gland function in patients with thyroid cancer treated with I-131. PATIENTS AND METHODS: The study group consisted of 71 patients (16 men, 55 women) with a mean age of 44 years (range, 16 to 73 years). Twenty-six (37%) patients were not given any radioiodine, and 18, 16, and 11 patients received doses of 100, 150, or 200 mCi (or higher), respectively. Parotid and submandibular glands were evaluated based on a four-grade scoring system. Correlation between the type of surgery, administered dose, time since therapy, subjective symptoms, and findings of salivary gland scintigraphy were evaluated. RESULTS: Subjective symptoms were questioned in 39 of the 45 patients who received radioactive iodine treatment. Fifty-four percent (21 of 39) of the patients reported xerostomia, of whom 86% (18 of 21) showed salivary gland dysfunction. Objective salivary gland dysfunction was observed in 69% (31 of 45) of patients. In 81% of the patients, the parotid glands were affected; in 13% of the patients, the submandibular glands were affected; and in 6%, both were affected ( < 0.000001). The frequency of salivary gland dysfunction showed a dose dependence to cumulative activity ( = 0.007). A greater complication rate was observed in patients with total thyroidectomy compared with subtotal surgery, although the correlation was not significant ( = 0.625). CONCLUSIONS: Parenchymal damage to the salivary glands induced by radioactive iodine treatment can be evaluated by salivary gland scintigraphy. The impairment is worse in the parotid glands and increases with the total dose.     

分化型甲状腺癌术后131I清甲效果的影响因素

利用131I清除甲状腺癌术后残留甲状腺组织(清甲)是分化型甲状腺癌(DTC)术后治疗中的重要步骤.清甲效果受诸多因素影响,包括口服131I的剂量、DTC的手术方式、术后甲状腺组织残留量、血清促甲状腺激素(TSH)与甲状腺球蛋白(Tg)水平、有无淋巴结及远处转移、手术距13I治疗时间的长短等.使用较大剂量131I进行清甲、采取甲状腺全切或近全切除术方式、131I治疗前较高水平的TSH,以及术后及时开始131I治疗等有助于提高清甲成功率.131I治疗前患者血清Tg水平偏高或存在转移灶,应适当加大131I治疗剂量.患者性别、年龄、病理类型等对清甲成功与否无明显影响.     

Respiratory distress caused by radioiodine therapy in patients with differentiated thyroid cancer

Respiratory distress accompanied by stridor is an uncommon complication of 131I radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours of treatment. This report presents three cases with papillary thyroid carcinoma in which 131I therapy caused this acute complication. One of them had no apparent risk for this complication such as the existence of remnant thyroid tissue or laryngeal problems before the treatment. These cases remind physicians that 131I therapy is not a simple, riskless procedure.