Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone.

The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC. METHODS: Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B). RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration. CONCLUSION: Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.     

The importance of recombinant human thyroid stimulating hormone in the follow-up and treatment of disseminated thyroid cancer after thyroidectomy

In patients operated for differentiated thyroid cancer (DTC), before thyroid remnant ablation and treatment of metastatic disease, thyroid hormones are withdrawn four to six weeks in order to induce an increase in serum thyroid stimulating hormone (TSH) of more than 25-30 microU/mL and thus to stimulate thyroid gland uptake and retention of iodine-131 ((131)I), given therapeutically. Secretion of thyroglobulin (Taug) is also increased. However, thyroid hormone withdrawal frequently causes clinical hypothyroidism. Recombinant human TSH (rhTSH) can provide TSH stimulation without withdrawal of thyroid hormones. The primary clinical utility of rhTSH has been for the post-surgical monitoring in patients with DTC but is currently an aid in thyroid remnant ablation and treatment of thyroid tumors with encouraging results. In this review we have briefly described the findings reported during the period 1994-2006 concerning the diagnostic and therapeutic usefulness of rhTSH in patients with DTC after total or near total thyroidectomy.     

Which thyroid cancer patients need periodic stimulation tests?

PURPOSE: Recurrences are frequent in thyroid cancer patients and long-term follow-up is therefore necessary. We evaluated the yield of rhTSH stimulation in three groups of patients, classified according to the UICC/TNM risk stratification and the results of first follow-up testing. METHODS: The study population comprised 129 patients referred for rhTSH testing. All had undergone first follow-up testing after thyroid hormone withdrawal (off-T4) within 1 year of 131I ablation. Negative first follow-up testing was defined as Tg <2 ng/ml and no neck uptake on 131I diagnostic whole-body scan. Seventy-five patients had stage I thyroid cancer and negative first follow-up testing (group A), 19 had stage I disease and positive first follow-up testing (group B), and 35 had stage II-IV disease (group C). RhTSH stimulation was performed an average of 6 years after first follow-up testing. RESULTS: 131I diagnostic scanning after rhTSH was negative in all 75 group A patients. Only one group A patient had detectable Tg after rhTSH injection (1.5 ng/ml), but Tg had also been detected at baseline in this patient (1.45 ng/ml). Given the absence of a response to stimulation, suggesting an interference, Tg was reassessed with a different technique and proved to be undetectable (<0.1 ng/ml). Stimulation with rhTSH in group B showed residual Tg in seven patients and residual 131I uptake in the thyroid bed in two patients, but none of these patients had signs of disease progression. Five group C patients (14%) had a positive rhTSH test result, and this was suggestive of disease progression in at least two cases. CONCLUSION: The first follow-up testing is essential for prognostic classification after 131I ablation of thyroid cancer. In stage I patients, undetectable Tg and negative 131I scan 1 year after ablation define a large population of subjects who have a very low risk of recurrence and who do not require further stimulation tests. In contrast, periodic rhTSH stimulation tests appear useful in higher-risk patients.     

重组人促甲状腺激素在甲状腺疾病诊治中的应用

重组人TSH (rhTSH)于1998年在国外进入临床应用,其临床适应证由辅助DTC患者的随访检查和检测逐渐扩展到辅助131I清除手术后残留甲状腺组织.近期研究表明,rhTSH在辅助131I治疗DTC转移灶、辅助131I治疗非毒性结节性甲状腺肿、提高18F-FDG PET对甲状腺癌的诊断效能及对先天性甲状腺功能减退症的病因鉴别诊断等多方面亦有应用潜力.     

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.     

Possible explanations for patients with discordant findings of serum thyroglobulin and 131I whole-body scanning.

The long-term monitoring of patients with differentiated thyroid carcinoma (DTC) is essential throughout the patient's life after total or near-total thyroidectomy followed by (131)I remnant ablation and thyroid hormone suppression of thyroid-stimulating hormone (TSH). Sensitive surveillance for DTC recurrence and metastases includes radioiodine diagnostic whole-body scanning (DWBS) and measurement of serum thyroglobulin (Tg) after endogenous or exogenous TSH stimulation. Serum Tg levels during thyroid hormone withdrawal (Tg-off) are usually well correlated with the results of DWBS. In general, undetectable Tg levels with negative DWBS (DWBS(-)) suggest complete remission, whereas detectable or elevated Tg concentrations are suggestive of the presence of (131)I uptake in local or distant metastases. However, DTC patients with discordant results of Tg measurement and (131)I WBS have been observed in the follow-up study. Negative (131)I DWBS and a positive Tg test (DWBS(-) Tg(+)) are found in most of these cases. Positive (131)I DWBS and a negative Tg test (DWBS(+) Tg(-)), though of uncommon occurrence, has also been demonstrated in a small but significant number of cases. With this scenario, one should first attempt to uncover a cause for possibly false-negative or false-positive (131)I WBS or serum Tg. Explanations for the discordance are speculative but should be scrutinized when confronted with discrepant data in a given patient.     

A clinical study of all-trans-retinoid-induced differentiation therapy of advanced thyroid cancer

OBJECTIVE: To evaluate the changes in differentiation markers and therapeutic effects in all-trans-retinoic acid (ATRA)-treated patients with dedifferentiated thyroid cancer. METHODS: Between September 2001 and July 2004 eleven patients were analysed retrospectively. They had dedifferentiated thyroid cancers (DTC) (four follicular, five papillary, two oxyphilic) and were selected for treatment with ATRA (1.00+/-0.09 mg x kg x d) for 30 or 60 days. All patients had advanced stage tumours with prior operative and radioiodine treatment. Extensive tumour invasion, distant metastatic spread, and insufficient or non-existent uptake of radioiodine precluded conventional therapeutic options. Changes in I uptake, response of target lesions, and serum thyroglobulin (Tg) levels were measured and compared in these patients before and after ATRA therapy. RESULTS: In 11 patients with DTC, iodine uptake was increased in four and there was a partial response (PR) of target lesions in five patients as well as two patients with stable disease. Tg was assessed in eight patients, in whom two responders showed increased radioiodine uptake or no change and decreased Tg level, as well as PR after ATRA-induced differentiation therapy. CONCLUSIONS: ATRA has an effect on the differentiation status of DTC and deserves further investigation.     

Examining recombinant human TSH primed 131I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol

Purpose

Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed ¹³¹I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients.

Methods

The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment.

Results

The mean effective half-life of ¹³¹I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p?=?0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but the difference was not found to be statistically significant (p?=?0.301). The mean tumor radiation absorbed dose per mCi was less during the rhTSH protocol (6.04 rad/mCi) than during the thyroid hormone withdrawal protocol (8.68 rad/mCi), and the difference was statistically significant (p?=?0.049), though visual analysis of the rhTSH posttherapy scans showed avid concentration of ¹³¹I in the metastatic sites and revealed more lesions in 30 % of the patients compared to the traditional large dose scan and equal number of lesions in 65 % of the patients. Visual analysis of the traditional large dose scan, rhTSH pretreatment scan, and rhTSH posttherapy scans showed that the traditional large dose scan is better compared to the rhTSH 1 mCi scan as it showed more lesions in 19 of 37 patients (51.35 %). rhTSH posttherapy scans were better compared to the traditional large dose scans and rhTSH pretreatment scans. More lesions were seen on rhTSH posttherapy scans in 11 of 37 patients (29.7 %) compared to the traditional large dose scans and in 24 of 37 (64.86 %) patients compared to the rhTSH 1 mCi scans. Our findings demonstrate that the rhTSH primed pretreatment scan undertaken at 24 h after diagnostic dose is suboptimal to evaluate whether a metastatic lesion concentrates ¹³¹I. The majority of these lesions demonstrated radioiodine accumulation in the posttreatment scan. Quality of life as assessed using EORTC QOL-3 forms clearly showed that rhTSH improved the quality of life of patients compared to the thyroid hormone withdrawal protocol. Functional scale and global health status were significantly better in the rhTSH protocol compared to the thyroid hormone withdrawal protocol (p?<?0.001). The mean symptom scale score was significantly higher in the thyroid hormone withdrawal protocol (45.25) compared to the rhTSH protocol (13.59) (p?<?0.001). Of the 20 patients, 4 (20 %) had more than 25 % increase in the TG value on follow-up. The median hospital stay of patients receiving ¹³¹I therapy with the rhTSH protocol was shorter (2 days, range 2–8 days) compared to the thyroid hormone withdrawal protocol (3 days, range 1–8 days) and the difference was found to be statistically significant (p?=?0.007). The mean serum creatinine level was significantly lower in the rhTSH protocol (0.826 mg/dl) than the thyroid hormone withdrawal protocol (0.95 mg/dl) (p?=?0.013), though the mean blood urea level of patients during the rhTSH therapy protocol was slightly higher (22.81 mg/dl) than during the thyroid hormone withdrawal protocol (21.91 mg/dl) without statistical significance (p?=?0.55). The mean serum TSH on day 2 of the rhTSH protocol was 140.99 μIU/ml (range 71–176 μIU/ml) compared to 72.62 μIU/ml (range 2.05–154 μIU/ml) in the traditional protocol after around 4–6 weeks of thyroid hormone withdrawal (p?<?0.05).

Conclusion

Overall, the rhTSH primed ¹³¹I therapy protocol was found to be feasible and a good alternative to the thyroid hormone withdrawal protocol in patients with metastatic DTC. The lesional dosimetry findings need to be further examined in subsequent studies. The rhTSH primed pretreatment scan at 24 h after diagnostic dose is suboptimal to determine whether a metastatic lesion concentrates ¹³¹I and the posttreatment scan is important for the correct impression.     

Therapeutic impact of 18F-FDG PET/CT in recurrent differentiated thyroid carcinoma

Purpose

¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) has proved effective in detecting recurrent or metastatic differentiated thyroid carcinoma (DTC) in the follow-up of operated DTC patients with high thyroglobulin (Tg) levels and negative findings on radioiodine whole-body scan. The aim of this retrospective study was to assess the impact of PET/CT on the planning of appropriate treatment for known recurrent disease in operated DTC patients.

Materials and methods

The study concerned 44 consecutive DTC patients (36 papillary, 8 follicular), who underwent total thyroidectomy and thyroid remnant ablation with ¹³¹I and PET/CT. All patients had proven or strongly suspected recurrent disease judging from neck ultrasound (US) and fine-needle aspiration cytology, and detectable basal Tg levels.

Results

PET/CT findings were positive in 25/44 patients (56.81 %) and negative in 19. A positive PET/CT result predicted resectable tumour recurrences in 19/25 patients, but also detected additional tumour sites that prompted changes to the treatment plan in 6/25 patients (24 %). A negative PET/CT result led to clinical monitoring for 11/19 patients (57.89 %).

Conclusions

PET/CT can help select patients, who might benefit from a tailored therapy by improving the detection of local recurrences not apparent on neck US or metastases.     

Is empiric 131I therapy justified for patients with positive thyroglobulin and negative 131I whole-body scanning results?

The long-term monitoring of patients with differentiated thyroid carcinoma (DTC) is essential throughout the patient's life after total or nearly total thyroidectomy followed by 131I remnant ablation and thyroid hormone suppression of thyroid-stimulating hormone (TSH). Sensitive surveillance for DTC recurrences and metastases includes radioiodine diagnostic whole-body scanning (DWBS) and measurement of serum thyroglobulin (Tg) levels after endogenous or exogenous TSH stimulation. Serum Tg levels during thyroid hormone withdrawal usually are correlated well with the results of DWBS. In general, Tg levels undetectable by DWBS suggest complete remission, whereas detectable or elevated Tg concentrations are suggestive of the presence of 131I uptake in local or distant metastases. However, DTC patients with a positive Tg test and negative 131I DWBS results (Tg+ DWBS-) have been observed in follow-up studies. The management of these cases begets controversy. METHODS: We electronically searched Medline (1966-2004.3), Embase (1984-2003), the Cochrane Library (2004, 2nd edition), CNKI (1994-2004), and CBM-DISC (1978-2004). We also manually searched the Chinese Journal of Isotopes, Radiologia pratica, and the Chinese Journal of Endocrinology and Metabolism. RESULTS: Ten serial observations and 3 nonrandomized controlled trials were found. The available data showed that of 314 patients who were treated empirically with 131I, 194 (62%) of 314 displayed pathologic uptake in the thyroid bed, lung, bone, mediastinum, and lymph nodes. In studies with Tg-on and Tg-off data, 171 (63%) of 271 patients achieved a decrease in Tg. CONCLUSION: On the basis of data from recent studies, 131I therapy should be individualized according to clinical characteristics. More significantly, a decrease in Tg levels was achieved in 63% of DTC patients with Tg+ DWBS-, suggesting that 131I therapy does have a therapeutic effect when the Tg level is considered an index of tumor burden. The 62% positive posttherapy whole-body scanning results also indicated that a therapeutic dose of 131I could reveal approximately one half of previously undiagnosed lesions in some patients. Therefore, 131I therapy may be justified in patients with Tg levels of > 10 microg/L and DWBS- and who are at high risk of any recurrence.     

Recombinant human TSH for the treatment of differentiated thyroid cancer metastatic to the spine

The diagnostic use of recombinant human TSH (rhTSH) in follow- up of differentiated thyroid cancer (DTC) is already approved, however its application in (131)I therapy is still to be evaluated. We report results obtained in four patients with DTC metastatic to central skeleton, in whom 5 courses of rtTSH aided 131I therapy were administered.     

131I治疗分化型甲状腺癌术后患者疗效影响因素研究

目的 探讨影响分化型甲状腺癌（DTC）患者术后首次131I清除残留甲状腺组织（简称清甲）疗效和多次131I治疗转移灶（清灶）疗效的因素。方法回顾性分析首次接受大剂量清甲治疗的患者46例（分为成功组与未成功组）资料、多次清灶治疗的患者40例（分为临床缓解组和未缓解组）资料,对数据进行t检验、t’检验、X^2检验或Fisher确切概率法筛选影响因素,并做Logistic回归分析。结果用单因素分析筛选出手术方式、残余甲状腺质量、促甲状腺激素（TSH）水平、手术至清甲治疗时间和存在转移灶是影响清甲效果的因素（X2=5．804、t’=-5．258、t=7．376、X^2=8．867、X2=8．615,P均〈0．05）。Logistic回归分析得到的清甲成功的拟合方程为Y=3．766—0．947x,（残余甲状腺质量）-3．149x：（淋巴结转移）-3．373x,（远处转移）。对临床缓解率行单因素分析显示：甲状腺乳头状癌显著高于甲状腺滤泡状癌,仅有淋巴转移灶显著高于有远处转移灶,甲状腺全切显著高于其他手术方式（Fisher确切概率法,X。=7．278,P〈0．05）;首次131I治疗前,临床缓解组的TSH水平明显高于未缓解组,甲状腺球蛋白（Tg）水平明显低于未缓解组（t=4．489、t=-4．906,P均〈0．01）。Logistic回归分析得到清灶成功拟合方程为：Y=-0．363＋0．065x4（TSH水平）-0．250x5（Tg水平）。结论DTC患者首次清甲疗效的影响因素有手术方式、残余甲状腺质量、TSH、手术至清甲治疗时间和有无转移灶;其中残留甲状腺组织少、无淋巴结转移和无远处转移是提高成功率的关键因素。DTC患者清灶疗效的影响因素包括病理类型、手术方式、转移灶的部位、TSH和Tg;其中首次131I治疗前有较高水平的TSH和较低水平的强是提搞缓解率的关键因素。     

分化型甲状腺癌的治疗进展

分化型甲状腺癌作为一种常见的低恶性肿瘤,通过“外科手术+131I治疗+甲状腺激素抑制治疗”三部曲的规范化治疗方案取得了良好的治疗效果。但部分治疗效果差的分化型甲状腺癌逐渐转化为低分化或失分化的难治性甲状腺癌,只能通过增敏和（或）再分化治疗来增加甲状腺癌细胞摄取131I的能力,以期提高131I治疗甲状腺癌的效果。对上述治疗手段无效的难治性甲状腺癌,靶向药物治疗技术的出现为其提供了广阔的治疗前景。笔者对使用增敏剂、再分化诱导剂和靶向药物治疗技术来提高分化型甲状腺癌治疗效果的研究进展进行了综述。     

基层医院分化型甲状腺癌131I规范化诊疗的临床体会

目的 分析安庆地区分化型甲状腺癌（DTC）的131I规范化治疗过程及现状,评价DTC在基层医院的治疗效果。 方法 收集2015年7月至2018年7月中国人民解放军海军安庆医院收治的219例DTC患者[男性48例、女性171例,年龄22~68（44.6±5.4）岁],观察131I治疗（所有患者行131I治疗前均停服左旋甲状腺素3~4周,无碘饮食,经过检查排除131I治疗禁忌后给予DTC个体化剂量口服131I治疗）后不同病理类型和是否出现转移的患者临床治疗效果,以及在治疗过程中存在的一些不规范现象;同时根据“皖西南地区核医学规范化治疗与诊断”学习班发放问卷调查表调查基层医院核医学科建设和规范化治疗开展现状,以及基层医师对DTC规范化治疗知识的掌握程度;结合门诊随访患者甲状腺球蛋白（Tg）的水平,以及甲状腺功能、甲状腺摄碘率、影像学检查的结果进行总结分析。 结果 219例DTC患者131I治疗后的平均有效率为98.6%（216/219）。在治疗过程中出现了57例患者不规范治疗现象,其中38例患者经二次手术再行131I治疗,7例转移患者经放疗或放疗后再行手术+131I治疗,8例患者“清甲”后颈部发现淋巴结转移,2例患者因促甲状腺激素（TSH）抑制不到位出现转移,2例患者（外院）未行Tg及 甲状腺球蛋白抗体的定期监测而发生转移。DTC规范化诊疗知识调查结果显示,安庆地区成立核医学的医院有2家,可以开展核素治疗的只有1家。在基层医院的医务人员中能掌握 DTC的规范化治疗知识者仅有30%（62/128） 。 随访患者Tg水平阴性187例、阳性32例,患者TSH水平控制均较理想。门诊患者甲状腺摄碘率检查结果均<1%,影像学检查结果多数为阴性。 结论 131I规范化治疗效果明显,虽然在治疗过程中还存在着一些不规范现象,但通过严格执行治疗制度,加强规范化诊疗意识,可以避免或减少不规范治疗现象的出现。     

Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer.

Recombinant human thyroid-stimulating hormone (rhTSH) recently was introduced as a radioiodine administration adjunct that avoids levothyroxine (LT-4) withdrawal and resultant hypothyroidism. The pharmacokinetics of 131I after rhTSH administration are known to differ from those after LT-4 withdrawal but are largely nondelineated in the radioiodine therapy setting. We therefore sought to calculate the red marrow absorbed dose of high therapeutic activities of 131I given after rhTSH administration to patients with metastatic or inoperable locally recurrent differentiated thyroid cancer. We also sought to evaluate the clinical and laboratory effects of this therapy on the bone marrow. METHODS: Fourteen consecutive patients received in total 17 131I treatments (7.4 GBq). Blood and urine samples were obtained at fixed intervals, and their activities were measured in a well counter. Based on blood activity, renal clearance of the activity, and residence times in red marrow and the remainder of the body, the red marrow absorbed dose was calculated using the MIRD schema. Additionally, we monitored for potential hematologic toxicity and compared platelet counts before and 3 mo after treatment. RESULTS: The mean +/- SD absorbed dose per unit of administered (131)I in the red marrow was 0.16 +/- 0.07 mGy/MBq. The corresponding total red marrow absorbed dose was 1.15 +/- 0.52 Gy (range, 0.28-1.91 Gy). In none of the patients was hematologic toxicity observed. The mean +/- SD platelet count (n = 13 treatments) was 243 +/- 62 x 10(9)/L before treatment and 233 +/- 87 x 10(9)/L 3 mo later, a slight and statistically insignificant decrease. After rhTSH-aided administration of high activities of 131I, the bone marrow absorbed dose remained under 2 Gy, the level long considered the safety threshold for all radioiodine therapy. CONCLUSION: Our specific findings imply that when clinically warranted, rhTSH should allow an increase in the therapeutic radioiodine activity. Such an increase might improve efficacy while preserving safety and tolerability; this possibility should be assessed in further studies.     

Thyroglobulin increment after thyroid hormone withdrawal is a reliable indicator for the detection of significant remnants or metastases in patients with differentiated thyroid carcinoma

Serum thyroglobulin (Tg) measurement has a pivotal role in the management of differentiated thyroid carcinoma (DTC). Serum Tg increment after thyroid hormone discontinuation seems to be a better predictor of tumor recurrence, however, minimal Tg increment may not be a specific marker. This study tries to evaluate the importance of different levels of Tg increment after thyroid hormone discontinuation. Fifty-five patients (46 females and 9 males with mean age of 41.40 yrs) with DTC, treated with total or subtotal thyroidectomy and radioiodine-131 ((131)I) were studied. Ninety-one per cent of the patients had papillary carcinoma. Serum Tg and thyroid stimulating hormone (TSH) were measured using high sensitive IRMA assays during thyroxine (T4) suppression and after discontinuation of T4 treatment. The mean time interval between Tg on T4 and off T4 was 110.29+/-53.43 days and less than 180 days in all patients. Serum Tg level was increased >or= 1 ng/ml in 25 patients after discontinuation of T4. Of these patients, 17 had metastatic disease or a detectable thyroid remnant. Of 16 patients with unchanged Tg (-1or= 7 ng/ml had residual disease or metastases. If DeltaTg was unchanged or decreased, the negative predictive value was 83.3%. The sensitivity of WB(131)IS was 63.6% for the detection of thyroid remnant or metastases. Our study indicates that DeltaTg is a more reliable indicator of remnant disease than on T4-Tg or off T4-Tg levels.     

The early detection of metastatic differentiated thyroid cancer using 131I total body scan and treatment with 131I

With the purpose of achieving early detection and performing 131I therapy for metastatic lesions of differentiated thyroid cancer, we studied the clinical findings in 132 patients who underwent 131I total body scanning (131I TBS) between 1981 and 1990. Metastatic lesions were detected only by 131I TBS in 24 (18%) of the 132 patients. Of the 49 patients treated with 131I for metastases, 27 (55%) underwent total thyroidectomy and then had their metastatic lesions treated by 131I less than one year later. In the remaining 22 patients (45%), the metastatic lesions were treated with 131I from 1 to 31 years (mean: 8.4 years) after the initial thyroidectomy. We determined the optimal timing of 131I TBS following radical thyroidectomy to be 3-4 weeks by sequential measurement of the serum thyroid hormones, TSH, and Tg, and determination of the 123I uptake in residual or metastatic cancer of the neck after thyroidectomy. 131I TBS with simultaneous serum Tg determination were performed in 52 patients with metastases. Scans were positive in 43 of the 52 (83%) and the serum Tg level was greater than 10 ng/ml in 46 of the 52 (88%). Serum Tg was elevated in 9 patients with negative scans, while low Tg levels were found in 6 patients with positive scans. 131I therapy was effective in 49 of the 65 treated patients (75%), including 5 cures. Two patients worsened and 6 died. These 8 patients were all older than 56 years of age. Post-therapeutic 131I TBS demonstrated unsuspected metastatic lesions in 7 patients and had a higher detection rate for metastatic lesions than diagnostic 131I TBS. We conclude that 131I TBS with simultaneous Tg determination should be performed to detect metastatic lesions in all patients following positively total thyroidectomy for differentiated thyroid cancer, and that 131I treatment should be given when positive 131I uptake is detected in metastatic or residual cancer.     

Fluorine-18 fluorodeoxyglucose dual-head positron emission tomography in the detection of recurrent differentiated thyroid cancer: preliminary results

In the follow-up of patients with thyroid cancer, it may be very difficult to identify the site of recurrence in the presence of persistently elevated or rising thyroglobulin (Tg) levels and negative iodine-131 whole-body scintigraphy (WBS). The aim of this study was to assess the feasibility of employing fluorine-18 fluorodeoxyglucose and a dual-head positron emission tomography (PET) camera to detect recurrent thyroid cancer in patients with elevated Tg levels and negative 131I WBS. Eleven patients suspect of having recurrent thyroid cancer (five males, six females; mean age 47 years; range 26-73 years) were studied with both 131I WBS and FDG using a dual-head PET camera. The suspicion that these patients had recurrent thyroid cancer was based on elevated Tg levels. Thyroid stimulating hormone (TSH) and Tg levels as well as antibodies to Tg were measured 3 weeks after the withdrawal of tri-iodothyronine. In patients in whom pathological uptake was seen on the PET images but who had no signs of recurrent thyroid cancer on WBS, ultrasonography and/or computed tomography or magnetic resonance imaging was performed followed by fine-needle aspiration cytology. The mean Tg and TSH levels after discontinuation of L-thyroxine were 156 ng/ml (range 4-815 ng/ml) and 84 mU/l (range 43-159 mU/l), respectively. None of the patients had antibodies to thyroglobulin. In seven out of ten patients with negative 131I WBS, FDG PET showed focally increased uptake in the head and neck region. In one patient, the site of increased uptake on the PET images corresponded with the site of increased 131I uptake. Malignancies with a diameter less than 1 cm (n = 3) were not depicted by either CT or US. It is concluded that detection of recurrent thyroid cancer by means of FDG dual-head PET is feasible in patients with elevated Tg concentrations and negative 131I WBS. The results justify a prolongation of the study.     

重组人促甲状腺激素用于低中危分化型甲状腺癌患者的术后评估:Ⅰ期临床研究报告

目的:评价我国自主研发的重组人促甲状腺激素(rhTSH)在辅助分化型甲状腺癌(DTC)患者¹³¹I治疗前后动态评估中的作用。方法:该Ⅰ期研究采用剂量递增设计,纳入2019年5月至2020年11月就诊于北京协和医院及郑州大学附属肿瘤医院的24例DTC患者(男5例、女19例,中位年龄41岁),根据国产rhTSH(简称rhTSH)使用方法分为4个剂量组[0.9 mg×1 d(A组),0.9 mg×2 d(B组),1.8 mg×1 d(C组),1.8 mg×2 d(D组)],每组6例。每例患者接受2个阶段自身对照研究,依次为rhTSH阶段及停用甲状腺激素(THW)阶段。评估rhTSH的安全性、耐受性、患者生活质量[甲状腺功能减退症(简称甲减)症状体征积分、简式心境状态量表(POMS)]、药效学[促甲状腺激素(TSH)及甲状腺球蛋白(Tg)水平、诊断性全身显像(Dx-WBS)]及药代动力学(达峰时间、峰浓度)特征。采用配对t检验或Wilcoxon符号秩检验进行统计分析。结果:4个剂量组均未观察到剂量限制性毒性事件、严重不良事件或≥3级的不良事件。rhTSH阶段的生活质量相关评分明显优于THW阶段:甲减症状体征积分[-53.00(-53.00,-53.00)与-39.50(-47.00,-23.00)分;S=119.50,P<0.001];简式POMS评分[(91.92±12.06)与(99.67±19.13)分;t=0.95,P=0.025]。rhTSH末次给药后24 h血清TSH水平从基线的0.04(0.02,0.11)mU/L升至150.00(105.20,173.31)mU/L;随着rhTSH剂量增加,各组TSH呈增高趋势。在THW阶段,患者需经中位时间23 d的THW方达TSH≥30 mU/L水平,THW阶段TSH水平为73.51(57.22,106.22)mU/L;Tg在rhTSH给药后从基线[0.10(0.10,0.41)μg/L]逐渐升高,48 h达峰值[0.85(0.12,3.01)μg/L],THW阶段Tg水平为0.88(0.15,8.04)μg/L;2个阶段诊断性全身显像结果一致率为95.8%(23/24)。结论:在辅助DTC术后评估中,国产rhTSH对患者显示出较好的安全性,患者生活质量较好;其可有效升高患者TSH水平,并快速刺激Tg分泌及残余甲状腺摄碘。     

Indium-111 octreotide scintigraphy for the detection of non-functioning metastases from differentiated thyroid cancer: diagnostic and prognostic value

In this prospective study, we evaluated the diagnostic and prognostic value of ¹¹¹In-octreotide scintigraphy (SRS) in papillary and follicular thyroid carcinoma (DTC) with increasing thyroglobulin (Tg) levels but no response to treatment with ¹³¹I. Twenty-three consecutive patients (13 female, 10 male; mean age 55 years, range 13–81 years) with progressive DTC were selected for the study. All patients had non-functioning metastases, defined by no or slight uptake of ¹³¹I in metastases. Diagnosis of tumour progression was based on rising Tg levels during follow-up and was confirmed by radiological examination. Uptake on SRS was scored from 0 to 4. Data on initial tumour stage, histology, age, gender, Tg values, TSH levels, ¹³¹I treatment doses, intervals and survival were gathered. Seven patients died during follow-up. The overall sensitivity for the detection of metastases was 74%. The sensitivity was better in patients in whom ¹³¹I whole-body scintigraphy did not show any abnormal uptake (82%; 14/17) than in patients with faint ¹³¹I uptake (50%; 3/6). The 10-year survival rate was significantly different between patients with an uptake score of 0 or 1 (100%) and those with an uptake score of 2, 3 or 4 (33%) (P=0.001). Gender, log Tg and uptake on SRS significantly correlated with survival, but in stepwise analysis, ¹¹¹In-octreotide uptake was selected as the most prognostic independent variable (hazard rate 6.25, P=0.006). We conclude that ¹¹¹In-octreotide scintigraphy is a valuable clinical tool for the detection of non-functioning DTC metastases. The uptake seems to correlate with prognosis and survival.