Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma

We evaluated the reliability of very low serum thyroglobulin (Tg) levels (less than 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of 131I therapy (99 patients), by performing whole body scans after a therapeutic course of 131I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 131I uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of 131I. In the majority of patients, especially those whose 131I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal.     

99mTc-sestamibi and 131I whole-body scintigraphy and initial serum thyroglobulin in the management of differentiated thyroid carcinoma.

99mTc-sestamibi whole-body scanning has been used in the postoperative assessment of differentiated thyroid carcinoma together with 131I whole-body scanning and serum thyroglobulin (Tg) estimation. This study compared 99mTc-sestamibi whole-body scanning with 131I whole-body scanning in the context of initial serum Tg levels of patients after total or near-total thyroidectomy who were taken off thyroxine suppression therapy and who had no 131I ablation before surgery. METHODS: A prospective study of 360 patients was undertaken. 99mTc-sestamibi whole-body scintigraphy was performed at least 5 wk after thyroidectomy and was followed by 131I whole-body scanning. The patients had no thyroxine suppression for 5 wk, and Tg was measured thereafter. Radiologic studies (chest radiography, CT, MRI, sonography, and bone scanning) and histopathologic examinations were performed to clarify the presence of metastases with positive uptake on either 99mTc-sestamibi scans or 131I whole-body scans. Positive scans were defined as those with the presence of thyroid remnants, lymph node disease, or metastases. RESULTS: Two hundred fifty-nine (71.9%) of the 360 patients had initial serum Tg levels < 30 ng/mL (group 1), whereas 101 (28.1%) had initial serum Tg levels > or = 30 ng/mL (group 2). Of the 259 group 1 patients, 82 had positive 99mTc-sestamibi scans and 113 had positive 131I scans; 71.7% of patients with positive 1311 scans also had positive 99mTc-sestamibi scans, and 98.8% of patients with positive 99mTc-sestamibi scans also had positive 131I scans. Of the 101 group 2 patients, 81 had positive 99mTc-sestamibi scans and 97 had positive 131I scans; 83.5% of patients with positive 131I scans also had positive 99mTc-sestamibi scans, and all patients with positive 99mTc-sestamibi scans also had positive 131I scans. Of those with initial serum Tg levels > or = 30 ng/mL (group 2), 27.2% had thyroid remnants and 68.8% had lymph node disease or metastases. 131I scanning detects more thyroid remnants and lung metastases than does 99mTc-sestamibi scanning. CONCLUSION: Our findings suggest that, compared with 131I scanning, 99mTc-sestamibi scanning is less sensitive in detecting thyroid remnants and lung metastases but appears to be more useful in the detection of lymph node disease before initial 131I treatment.     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4–16 years by means of regular Tg measurements, ¹³¹I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9±310.6 vs 15.9±19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of ¹³¹I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, ¹³¹I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up. Received 26 October 1998 and in revised form 12 June 1999     

The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer

A strict and careful strategy has to be adopted to cure thyroid cancer. Diagnostic iodine-131 whole-body scan (WBS) and serum thyroglobulin (Tg) are important tools to detect thyroid remnants after thyroidectomy and radioiodine therapy. The aim of this retrospective study was to compare the relative sensitivity of WBS and Tg in the detection of thyroid remnants or metastases and to evaluate the predictive value of Tg in the clinical and scintigraphic course of the disease. Ninety-three patients were followed up after total thyroidectomy and the administration 4–6 weeks later of an ablative dose of 100 or 150 mCi¹³¹I. Eighty-five percent of the patients were free of regional or distant metastases. The follow-up scheme included clinical examination of the patient followed by WBS, Tg, thyroid-stimulating hormone and free thyroxine measurements performed 4 weeks after thyroxine withdrawal and the observance of a low-iodine diet for at least 1 week. WBS (+) patients received a 100- or 150-mCi therapeutic dose of¹³¹I. All patients were further followed up in the same way every 6 months until both WBS and Tg became negative, and thereafter at 1-, 2- and 4-year intervals. Six months after the postoperative radioiodine treatment (first visit), the sensitivity of WBS and Tg was 87% and 26% respectively. Among patients who were WBS(+) at the first visit, 95% of those who were Tg(-) and 47% of those who were Tg(+) had become disease-free at a median of 4 years after surgery (²=13.6;P<0.05). Patients whose tests were both positive required more radioiodine to be cured (335±90 vs 250±95 mCi;P<0.05). Our data indicate that in early diagnosed thyroid cancer, serum Tg measured 6 months after the postoperative¹³¹I ablative dose is less sensitive than WBS for the demonstration of persistence of residual thyroid tissue but provides predictive information on the disease course. WBS(+) and Tg(-) patients are cured earlier and with less radioiodine than those who remain Tg(+).     

Differentiated thyroid cancer: comparison of therapeutic iodine 131 biological elimination after discontinuation of levothyroxine versus administration of recombinant human thyrotropin

The biological elimination of therapeutic 131I in patients with differentiated thyroid cancer (DTC), post total or near-total thyroidectomy, was compared after withholding levothyroxine suppression against administration of recombinant human thyrotropin without stopping levothyroxine. In 163 patients (group G1) levothyroxine was withheld before 131I therapy: in 138 patients the tumor was limited to the thyroid bed (group G1.1) and in 25 patients metastases were present (group G1.2). A second group of patients (G2; n = 28) received 131I therapy after administration of recombinant human thyrotropin without stopping levothyroxine. Mean retained 131I activity (as a percentage of the administered dose) was 5%-29% (group G1.1), 20%-43% (group G1.2) and 1%-17% (group G2). The effective half-life of 131I was 0.59-0.69 days (group G1.1), 0.87-1.22 days (group G1.2) and 0.38-0.44 days (group G2). In conclusion, the use of recombinant human thyrotropin to prepare patients with thyroid cancer for therapy with 131I shortens its effective half-life and reduces its retained activity compared to preparation with discontinuation of levothyroxine suppression.     

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.     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma.

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4-16 years by means of regular Tg measurements, (131)I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9+/-310.6 vs 15.9+/-19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of (131)I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, (131)I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up.     

Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma

Radioactive iodine (¹³¹I) has been found to be more sensitive and more specific than thallium-201 for the detection of distant metastases and thyroid remnants in the neck in cases of well-differentiated thyroid carcinoma. ²⁰¹Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative ¹³¹I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of ²⁰¹Tl imaging in localizing metastases or recurrence in patients with well-differentiated thyroid carcinoma, and (2) evaluate the false-positive and false-negative results of ¹³¹I and ²⁰¹Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative ²⁰¹Tl and ¹³¹I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. ²⁰¹Tl imaging was performed before the ¹³¹I studies. Of the 62 patients who underwent ²⁰¹Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the ²⁰¹Tl imaging studies tended to be older, were mor often male, had higher Tg levels and had a higher recurrence rate. Of these 24 patients, ten had negative diagnostic or therapeutic ¹³¹I scans. Concurrently, serum Tg levels were less than 5 ng/ml in five of these ten patients. Three patients were deemed false positive by ²⁰¹Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative ²⁰¹Tl scans, 11 had positive findings on ¹³¹I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on ¹³¹I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative ²⁰¹Tl and ¹³¹I scans, 15 had elevated serum Tg levels. Among these, local recurrence followed by lung metastases was manifested in a 49-year-old male with papillary thyroid carcinoma. In conclusion, both ¹³¹I and ²⁰¹Tl scans are useful in the detection of recurrence or distant metastasis of well differentiated thyroid cancers. ²⁰¹Tl scan could in particular be used in patients with a negative ¹³¹I scan in conjunction with an elevated Tg level. Received 16 January and in revised form 8 April 1998     

131I全身显像及血清甲状腺球蛋白测定在分化型甲状腺癌治疗随访中的作用

目的 评价131I全身显像联合血清甲状腺球蛋白(Tg)测定在分化型甲状腺癌(DTC)131I治疗随访中的临床应用价值。 方法 153例经手术病理确诊为DTC的患者,均在术后接受了1次以上的131I治疗,每次剂量为1.85~9.25 GBq,131I治疗前测定血清Tg,治疗5 d后进行131I全身显像。 结果 153例行131I治疗的DTC患者共行血清Tg和131I全身显像检查各为262次,其中55.6%(85/153)的患者的血清Tg水平与131I全身显像均异常,13.7%(21/153)的患者两者均为正常,30.7%(47/153)的患者两者结果不一致,不一致的47例患者经其他影像学检查证实19例131I全身显像异常的患者中有13例异常,28例血清Tg异常的患者中有25例异常。血清Tg诊断DTC转移的灵敏度和特异度分别为89%(110/123)和90%(27/30),而131I全身显像的灵敏度和特异度分别为79.6%(98/123)和80%(24/30)。 结论 DTC手术及131I治疗后,常规进行血清Tg测定和131I全身显像检查,对术后判定复发转移灶及制定最佳131I诊疗计划、评价131I疗效具有重要的临床应用价值。     

Critical evaluation of serum thyroglobulin (Tg) levels during thyroid hormone suppression therapy versus Tg levels after hormone withdrawal and total body scan: Results in 291 patients with thyroid cancer

Serum thyroglobulin (Tg) levels were measured during thyroid-hormone suppressive therapy in 291 patients who had been treated for well-differentiated thyroid carcinoma. The findings were compared with those of a subsequent total body scan (TBS) and with Tg levels measured after thyroid-hormone withdrawal. Of the patients with low Tg levels during suppressive therapy, 91.6% were subsequently shown to be free of disease or to have only remnants in the thyroid bed, whereas 8.4% had metastases (flase-negative). Of the patients with false-negative findings, 89.3% had nodal metastases; 60.8% of the patients with nodal metastases exhibiting radioiodine uptake and only 23% of those with nonfunctioning nodal metastases had low Tg levels during suppression therapy. After thyroidhormone withdrawal, all but 1 of the patients with nodal metastases had high Tg levels. All but 2 of the patients with distant metastases had high Tg levels during suppression therapy; 1 of these 2 patients exhibited high Tg levels after T₃ withdrawal. No differences between Tg levels in patients with functioning and non-functioning metastases were found. Our study indicates that Tg assays performed during suppressive therapy have a fairly good predictive value and can be used as a general guide in the follow-up of thyroid cancer. However, since most differentiated metastases produce Tg only when stimulated by thyroid-stimulating hormone, measurements of Tg levels after the discontinuation of suppressive therapy would also seem to be necessary.     

131I治疗分化型甲状腺癌转移灶中甲状腺球蛋白测定和131I-全身显像的意义

目的探讨分化型甲状腺癌转移灶治疗中131I-全身显像(131I-WBS)和甲状腺球蛋白(Tg)测定的意义。方法39例分化型甲状腺癌患者术后4～6周用131I行首次清除残余甲状腺治疗,3～6个月后重复治疗,治疗中131I-WBS和Tg测定同期完成。结果在首次清除残余甲状腺治疗时显像发现淋巴、肺及骨转移灶有11例,其余转移灶于重复治疗时发现。131I治疗分化型甲状腺癌转移灶,以淋巴转移效果最好,肺转移次之,骨转移最差。有8例患者(20.5%)Tg测定与131I-WBS不符。结论131I治疗分化型甲状腺癌转移灶效果好,患者存活率高;131I-WBS和Tg测定在分化型甲状腺癌随访中应联合应用,互相补充。     

Critical evaluation of serum thyroglobulin (Tg) levels during thyroid hormone suppression therapy versus Tg levels after hormone withdrawal and total body scan: results in 291 patients with thyroid cancer

Serum thyroglobulin (Tg) levels were measured during thyroid-hormone suppressive therapy in 291 patients who had been treated for well-differentiated thyroid carcinoma. The findings were compared with those of a subsequent total body scan (TBS) and with Tg levels measured after thyroid-hormone withdrawal. Of the patients with low Tg levels during suppressive therapy, 91.6% were subsequently shown to be free of disease or to have only remnants in the thyroid bed, whereas 8.4% had metastases (false-negative). Of the patients with false-negative findings, 89.3% had nodal metastases; 60.8% of the patients with nodal metastases exhibiting radioiodine uptake and only 23% of those with nonfunctioning nodal metastases had low Tg levels during suppression therapy. After thyroid-hormone withdrawal, all but 1 of the patients with nodal metastases had high Tg levels. All but 2 of the patients with distant metastases had high Tg levels during suppression therapy; 1 of these 2 patients exhibited high Tg levels after T3 withdrawal. No differences between Tg levels in patients with functioning and non-functioning metastases were found. Our study indicates that Tg assays performed during suppressive therapy have a fairly good predictive value and can be used as a general guide in the follow-up of thyroid cancer. However, since most differentiated metastases produce Tg only when stimulated by thyroid-stimulating hormone, measurements of Tg levels after the discontinuation of suppressive therapy would also seem to be necessary.     

Iodine-123 as a diagnostic imaging agent in differentiated thyroid carcinoma: a comparison with iodine-131 post-treatment scanning and serum thyroglobulin measurement

Purpose Using ¹²³I for diagnostic purposes avoids the risk of stunning for subsequent radioiodine treatment and affords an excellent image quality. In this study we assessed the role of ¹²³I in comparison with ¹³¹I post-treatment imaging in patients with thyroid cancer. Methods We compared a total of 292 ¹²³I scans with their corresponding post-treatment ¹³¹I images. Patients received a therapeutic dose of ¹³¹I following diagnostic scanning with 50–111 MBq of ¹²³I. All patients were in a hypothyroid state (>30 μIU/l) before radioiodine administration for either diagnostic or therapeutic purposes. Results In 228 out of 263 patients with a positive diagnostic scan, ¹²³I whole-body scan findings were concordant with those of corresponding post-treatment ¹³¹I images (concordance rate 87%). However, there were 44 additional foci of abnormal uptake on post-treatment ¹³¹I scans in 22 discordant cases with no impact on therapeutic management of the patients. In 13 patients, there was at least one new site on post-treatment images that had been missed on pretreatment ¹²³I images. Twenty-nine patients with a negative diagnostic scan were treated with ¹³¹I owing to a high serum thyroglobulin level (range 11.3–480 ng/ml). Radioiodine uptake sites were seen in eight post-treatment scans. In 21 pairs of whole-body scans, both the pre- and the post-treatment scan were negative (concordance rate 72.4%). Conclusion ¹²³I scanning is comparable to high-dose ¹³¹I post-treatment imaging in thyroid carcinoma patients, and ¹²³I offers excellent image quality as a diagnostic agent. It avoids disadvantages such as stunning before treatment and delivery of a high radiation dose to patients.     

Sensitivity of 123I whole-body scan and thyroglobulin in the detection of metastases or recurrent differentiated thyroid cancer

Primary treatment of differentiated thyroid carcinoma consists of total thyroidectomy followed by ablation of thyroid tissue remnants and possible metastases by means of radioactive iodine. After complete destruction of remnants, metastases or recurrence can be detected by measurement of the serum thyroglobulin level as well as by radionuclide methods. Here we report on the sensitivity of diagnostic 123I scintigraphy and serum thyroglobulin measurement for tumour detection in patients with proven recurrence or metastases. Fifty-five patients who received their first high activity (1,850-5,550 MBq) of 123I therapy after total thyroidectomy and 131I ablation were included in the study. The thyroglobulin level was measured both during TSH-suppressive L-thyroxine therapy (Tg-on) and 4-6 weeks after L-thyroxine withdrawal (Tg-off, TSH>20 mU/l). Prior to treatment, whole-body scanning (WBS) was performed 24 h after the administration of 111-370 MBq 123I. The therapeutic activity of 1,850-5,550 MBq 131I was administered within 24 h after diagnostic scanning. The mean interval between 131I therapy and post-therapeutic WBS was 8.6 days (range 3-15 days). The sensitivity of WBS, Tg-on and Tg-off was 75%, 82% and 98%, respectively. The overall sensitivity of the combination of Tg-on with WBS and of Tg-off with WBS was 95% and 100%, respectively. In 12 out of 51 cases either Tg-off or Tg-on or both Tg-on and Tg-off levels were elevated while 123I-WBS was negative. More lesions were visible on the post-therapeutic 131I scan than on the corresponding diagnostic 123I scan (n=13). Tg values increased significantly (P<0.0001) after thyroid hormone withdrawal. Early treatment of distant metastases or tumour remnants of differentiated thyroid carcinoma is favoured and 131I treatment should also be considered in patients with a negative WBS but positive serum Tg level. The finding of a positive Tg-off level, which is clearly above the corresponding Tg-on value, is sufficient to make this decision. Additional diagnostic 123I WBS will not improve sensitivity.     

Decreased uptake after fractionated ablative doses of iodine-131

Purpose In an attempt to obviate the necessity for hospitalisation, the ablative dose of ¹³¹I in the treatment of thyroid cancer is divided into two or three fractions at weekly intervals in some hospitals with no special bed for ¹³¹I treatment. Thyroid stunning has been observed in patients receiving a ¹³¹I dose between 74 and 370 MBq (2–10 mCi). However, the influence of ¹³¹I uptake after administration of a higher dose, such as 1,110–1,850 MBq of ¹³¹I, has never been reported. In this study, we evaluated the degree of reduction in ¹³¹I uptake after patients received 1,480 MBq of ¹³¹I and evaluated the clinical value of fractionated ablative doses of ¹³¹I.Methods Thirty-five patients with functional thyroid cancer received a total of 4,440 MBq (120 mCi) of ¹³¹I which was divided into three fractions administered at weekly intervals. In all patients two ¹³¹I whole-body scans were performed. The first scan was performed directly prior to the second dose of ¹³¹I (7 days after the first administration of ¹³¹I), and the second scan was performed 7 days after the second administration of ¹³¹I and directly prior to the third administration. Regions of interest including the neck and lungs were drawn to calculate the uptake of ¹³¹I in the thyroid remnant and possible cervical lymph node and lung metastases.Results The mean uptake of ¹³¹I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. The decrease in ¹³¹I uptake was significant in all patients except the two with lung metastases. In the two patients with lung metastases, no definite evidence of decreased uptake was noted; the uptake of ¹³¹I in the lung metastases even increased on the second ¹³¹I image in one of these patients. After administration of 1,480 MBq of ¹³¹I, the decreased uptake was significant in all neck lesions but not in lung metastases.Conclusion The use of fractionated ablative doses of ¹³¹I is not to be recommended in patients without lung metastases. However, the influence of fractionated ablative doses of ¹³¹I in patients with lung metastases is worthy of further study.     

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.     

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery

The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and ¹³¹I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and ¹³¹I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to ¹³¹I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, ^99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the ¹³¹I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with ¹³¹I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with ¹³¹I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose ¹³¹I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to ¹³¹I scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of ¹³¹I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT. Received 21 October and in revised form 20 December 1999     

Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy

In our hospital, a 24-h radioiodine-131 (¹³¹I) uptake-related ablation strategy is used in patients with differentiated thyroid cancer to destroy thyroid remnants after primary surgery. In this strategy, low doses of ¹³¹I are used, but data in the literature on its efficacy are conflicting. Therefore, we performed the present study to evaluate the clinical outcome of this ablation strategy. In this study, patients (n=235) were selected who underwent thyroidectomy for differentiated thyroid cancer, followed by an ablative dose of ¹³¹I. Approximately 6 months after ablation, treatment efficacy was evaluated using radioiodine scintigraphy and thyroglobulin (Tg) measurements. Successful ablation was defined as the absence of radioiodine uptake in the neck region (criterion 1). Tg values were determined 3–12 months after ablation (criterion 2). Based on criterion 1, unsuccessful ablation was found in 43.0% of cases. Pre-treatment uptake values were statistically significantly lower (P=0.003) in successfully ablated patients (mean 5.4%) than in unsuccessfully ablated patients (mean 8.2%). Based on criterion 2, unsuccessful ablation was found in 52.4% of patients. The uptake-related ablation strategy, using low doses of ¹³¹I, shows a relatively high treatment failure rate. Based on these results it is suggested that a lower ablation failure rate could be achieved by applying higher ¹³¹I doses in the ablation of thyroid remnants in differentiated thyroid carcinoma patients. In the case of lymph node metastases a further dose adjustment may be advisable.     

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.     

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.