Radioiodine dose for remnant ablation in differentiated thyroid carcinoma: a randomized clinical trial in 509 patients

Remnant ablation can be achieved by either administering an empiric fixed dose or using dosimetry-guided techniques. Because of the technical and logistic difficulties, most centers have adapted the fixed-dose or standard-dose technique for remnant ablation using (131)I. In the late 1970s, low-dose (131)I remnant ablation was introduced, and subsequently many centers confirmed the effectiveness of such therapy. However, the optimal dose (administered activity) of (131)I for remnant ablation is not yet settled. In a randomized clinical trial to find out the smallest possible effective dose for remnant ablation in cases of differentiated thyroid carcinoma, between July 1995 and January 2002, 565 patients were randomized into eight groups according to (131)I administered activity, starting at 15 mCi and increasing activity in increments of 5 mCi until 50 mCi. In the postrandomization phase, 56 patients were excluded from the study for various reasons, and final analysis was done with 509 patients. The mean age of the patients was 37.5 +/- 12.7 yr with a female to male ratio of 2.6. The surgical procedure was total/near-total thyroidectomy in 72% and subtotal or hemithyroidectomy in the rest. Histology was papillary thyroid carcinoma in 80.6% of patients and follicular thyroid carcinoma in the rest. With one dose of (131)I, remnant ablation was achieved in 59.6, 63.6, 81.4, 83.6, 79.4, 78.3, 84.4, and 81.8% of patients in the 15- to 50-mCi groups, respectively (overall ablation rate, 77.6%). The successful ablation rate was statistically different in patients receiving less than 25 mCi of (131)I compared with those receiving at least 25 mCi [63 of 102 (61.8%) vs. 332 of 407 (81.6%); P = 0.006]. However, there was no significant intergroup difference in outcome among patients receiving 25-50 mCi of (131)I. Patients with small tumor size (相似文献   

Radioiodine ablation and therapy in differentiated thyroid cancer under stimulation with recombinant human thyroid-stimulating hormone

We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.     

Successful use of recombinant human thyrotropin in the therapy of pediatric well-differentiated thyroid cancer

Recombinant human TSH (rhTSH) is increasingly employed in stimulating radioiodine (131I) uptake in adults with well-differentiated thyroid cancer (WDTC) for diagnostic scanning, and preliminary evidence suggests that it may have a role in radioactive iodine therapy as well. However, the safety and efficacy of rhTSH in children have not been determined. We report a case of a 13-yr-old boy presenting with metastatic papillary thyroid cancer. After total thyroidectomy, his serum thyroglobulin (Tg) was 302 ng/ml (3.7-49.3) with negative antibodies. A diagnostic whole body scan (WBS) demonstrated multiple foci of uptake in the neck, thyroid bed and chest. His serum TSH only increased to 14.2 microU/ml (0.3-4.7) upon thyroid hormone withdrawal. Therefore, the patient was given 0.9 mg rhTSH every 24 h for two consecutive days and treated with 102 mCi 131I 24 h after the last rhTSH injection. Six months later, the patient was again conditioned with rhTSH and treated with an additional 150 mCi 131I. This treatment effectively reduced his tumor load with his most recent (10 months after the second ablation) serum Tg measuring 19.3 ng/ml. This case highlights the safety and effectiveness of rhTSH stimulated radioablation in pediatric WDTC, and proposes to invite controlled studies to further investigate pediatric rhTSH use, particularly in patients in whom thyroid hormone withdrawal is not a viable option.     

Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation

The main steps in the management of differentiated thyroid cancer are thyroidectomy, treatment with iodine-131 ((131)I), and follow-up with whole-body scanning (WBS) and serum thyroglobulin (Tg) determination. Both (131)I treatment and follow-up require maximum stimulation of normal or pathological thyroid remnants by TSH. The use of recombinant human TSH (rhTSH) has been shown to be useful for follow-up, whereas previous reports are not univocal regarding the use of (131)I postsurgical ablation of thyroid remnants, at least when low doses (30 mCi) of (131)I are administered. A possible explanation for the diminished effectiveness of (131)I treatment after rhTSH may be the interference of iodine content of L-thyroxine (L-T4) therapy during the protocol of administration of rhTSH. We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. The study included two groups of patients: group 1 included 16 patients with differentiated thyroid cancer (15 papillary cancers and 1 follicular cancer, stages I and II), who were treated with 30 mCi (131)I with the aid of rhTSH, using the standard protocol but stopping L-T4 as stated previously; and group 2 included 24 patients with the same features (histology and stage) of disease treated with 30 mCi in the hypothyroid state after L-T4 withdrawal. In both groups, serum TSH reached a very good stimulation level [76-210 U/liter (mean, 112 +/- 11 SE) and 38-82 U/liter (mean, 51 +/- 3 SE), respectively]. At the first WBS (after (131)I treatment), all patients showed thyroid remnants. Furthermore, two patients of the first group and three patients of the second group showed lymph node metastases. After 1 yr, all patients were studied again and underwent WBS with a tracer dose of (131)I and serum Tg measurement using rhTSH with the same protocol in both groups. The percentage of ablation (undetectable Tg and a negative WBS) was higher, although not reaching statistical significance, in patients treated with rhTSH: 81.2% in patients treated by rhTSH withdrawal and 75.0% in patients treated by L-T4 withdrawal, respectively. No patient experienced symptoms of hypothyroidism during the 4 d of L-T4 interruption, and serum T4 remained in the normal range. Urinary iodine was analyzed in both groups and compared with a control group of patients who received, for diagnostic purposes, rhTSH without stopping L-T4. In the first group, urinary iodine was 47.2 +/- 4.0 microg/liter (mean +/- SE; P = 0.21 vs. the second group, P = 0.019 vs. control group). In the second group, urinary iodine was 38.6 +/- 4.0 microg/liter (mean +/- SE; P < 0.001 vs. control group); urinary iodine in the control group was 76.4 +/- 9.3 microg/liter (mean +/- SE). Our data show that rhTSH, as administered in the protocol stated previously, allows at least the same rate of ablation of thyroid remnants when low doses (30 mCi) of (131)I are used. The possible role of interference of iodine content in L-T4 is not surprising if we consider that the amount of iodine in 30 mCi is negligible (5 microg) compared with the amount of iodine content in a daily dose of T(4) ( approximately 50 microg). The cost of rhTSH seems modest compared with the high cost of complex therapeutic regimens in other areas of oncology and in consideration of the well-being of patients and of the high level of effectiveness of the treatment.     

Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer?

A diagnostic iodine-131 (131I) total body scan (TBS) is usually recommended 6 to 12 months after thyroid ablation for differentiated thyroid carcinoma. Its usefulness was evaluated in 256 consecutive patients treated and followed up at the Institut Gustave Roussy for papillary (n = 200), well differentiated (n = 27), or poorly differentiated (n = 29) follicular thyroid carcinomas. All patients underwent a near-total or total thyroidectomy and 131I ablation with 3.7 GBq (100 mCi). No TBS was performed before 131I ablation. The TBS performed after the administration of 131I to destroy the thyroid remnants showed uptake (<2%) limited to the thyroid bed. A diagnostic 131I-TBS was obtained after withdrawal of T4 treatment, with either 74 MBq (2 mCi; n = 82) or 185 MBq (5 mCi; n = 174), 6 to 12 months after initial treatment, with serum thyroglobulin (Tg) determination. No interference in the Tg assay was found in these 256 patients. Uptake in the thyroid bed was not detected (total ablation) in 236 patients, was visible but too low to be measured in 19 patients, and attained 1% in only 1 patient. No uptake was found outside the thyroid bed. The serum Tg level, once thyroid hormone treatment had been withdrawn, was below 1 ng/mL in 210 patients, ranged from 1-10 ng/mL in 31 patients, and was above 10 ng/mL in 15 patients. A 131I-TBS performed with 3.7 GBq in nine patients with a Tg level above 10 ng/mL, showed foci of uptake outside the thyroid bed in three patients; lung metastases were demonstrated by a CT scan in another patient, and palpable lymph node metastases were found in one patient. In conclusion, a diagnostic 131I-TBS with 74-185 MBq performed 1 yr after thyroid ablation demonstrated no abnormal uptake; it did not correlate with results of Tg determination and only confirmed the completeness of thyroid ablation. The serum Tg level obtained after withdrawal of T4 treatment permits the selection of patients with a Tg level exceeding 10 ng/mL, for scanning with 3.7 GBq (100 mCi).     

Incidentally Visualization of the Thymus on Whole-Body Iodine Scintigraphy: Report of 2 Cases and Review of the Latest Insights

Radioiodine uptake is not commonly seen by the thymus gland. On the contrary, the gland is slowly replaced by fat after puberty. Herein, we present 2 patients with papillary thyroid carcinoma, follicular variant, and cervical lymph node involvement. After total/near-total thyroidectomy, the patients received ¹³¹I for ablation therapy. On posttreatment radioiodine scintigraphy, mediastinal ¹³¹I uptake was noted that finally was histologically/anatomically diagnosed as thymus gland uptake. It should be borne in mind as a potential cause of false-positive whole-body ¹³¹I scintigraphy.     

An overview of the management of papillary and follicular thyroid carcinoma.

Long-term survival rate for papillary and follicular carcinoma is more than 90%, but this varies considerably among subsets of patients. About 30% of patients, however, develop tumor recurrence, depending on the initial therapy. Two-thirds of the recurrences occur within the first decade after therapy, but the others may appear years later. We found that among patients with recurrent cancer, 30% could not be fully eradicated and another 15% died of disease. Tumor recurred outside the neck in 21% of our patients, most commonly in the lungs (63%), which resulted in death in about half the patients. Mortality rates are lower when recurrences are detected early by radioiodine scans rather than by clinical signs. We believe that the best treatment for most patients with differentiated thyroid carcinoma is near-total thyroidectomy followed by 131I ablation of the thyroid remnant, which in our experience reduces the recurrence rate, improves survival and facilitates follow-up. A long delay in initiating this therapy has an adverse and independent effect on prognosis, more than doubling the 30-year cancer mortality rate. If only partial lobectomy has been performed, it is best to consider completion thyroidectomy for lesions 1 cm or larger because of the high rate of residual carcinoma in the contralateral lobe. Completion thyroidectomy and 131I whole-body scanning allows for the diagnosis and treatment of unrecognized carcinoma and when performed early, results in significantly fewer lymph node and hematogenous recurrences and enhances survival. A large and growing number of studies demonstrates decreased recurrence of papillary carcinoma and decreased disease-specific mortality attributable to 131I therapy. On the basis of our observations and other studies, we believe that an aggressive approach to initial management and follow-up may render nearly 90% of the patients permanently free of disease. Periodic follow-up should be done with whole-body scanning and serum thyroglobulin (Tg) measurements, performed either during thyroid hormone withdrawal or by recombinant human thyrotropin (TSH)-stimulated scanning and Tg measurement. A scheme for follow-up management is presented.     

Follow-up of differentiated thyroid carcinoma

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.     

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin.

Radioiodine ablation (RA) of normal thyroid remnants after thyroidectomy for differentiated thyroid carcinoma improves the sensitivity of subsequent radioiodine scans and serum thyroglobulin measurements for detection of residual thyroid carcinoma. Local cancer recurrences are also lower after RA. One standard preparation for RA involves rendering the patient hypothyroid in order to stimulate endogenous thyrotropin (TSH) secretion and sodium iodide symporter (NIS) activity. An alternative approach is to prescribe thyroxine after thyroidectomy and to stimulate NIS with exogenous recombinant human thyrotropin (rhTSH). This latter approach was used in 10 patients at our medical center. Complete resolution of all visible 131I thyroid bed uptake was achieved in all when follow-up scans were performed 5 to 13 months later. This approach has the potential to successfully ablate thyroid remnants without the need to induce hypothyroidism.     

Low dose radioiodide thyroid ablation in postsurgical patients with thyroid cancer

Sixty-four patients with well-differentiated carcinoma of the thyroid were treated with initial high (80 to 100 mCi) or low (less than 30 mCi) doses of I¹³¹ after bilateral subtotal thyroidectomy. A total of 36 patients in the various histologic categories were initially treated with the low dose of I¹³¹ (group 1), and a total of 28 patients were treated with the higher dose (group 2). Disease-free criteria were no visible tissue in the neck or body, a protein-bound radioactive iodine (PBI¹³¹) of less than 0.005 per cent per liter at seven days and/or whole body retention of less than 3 per cent at seven days. Of the patients receiving less than 30 mCi (group 1), 56 per cent with papillary carcinoma, 67 per cent with follicular carcinoma and 56 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Of the patients receiving the higher dose of I¹³¹ (group 2), 67 per cent with papillary carcinoma, 50 per cent with follicular carcinoma and 67 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Disease-free mean follow-up time was 5.17 years (group 1) and 5.82 years (group 2). There was no statistical difference in these mean follow-up times, nor was there a statistical difference in the net (total minus initial) dose of I¹³¹ needed to render the patient disease-free. These data demonstrate that low dose I¹³¹ therapy is as effective as the larger more routine doses of I¹³¹ given in this disease.     

Post-surgical ablation of thyroid residues with radioiodine in Ukrainian children and adolescents affected by post-Chernobyl differentiated thyroid cancer.

Post-surgical ablation of thyroid residues with 131-iodine (131-I) is usually recommended after near-total thyroidectomy in high-risk patients, including children, with differentiated thyroid cancer (DTC). We report here the results of post-surgical radioiodine thyroid ablation in 249 children and adolescents of Ukraine with post-Chernobyl DTC initially treated with near-total thyroidectomy at the Institute of Endocrinology and Metabolism in Kiev, during a 2-year period. The patients' age at the time of the Chernobyl accident (1986), ranged from <1 to 14 yr in 223 subjects (children) and from 15 to 18 yr in 26 subjects (adolescents). Six weeks after surgery a diagnostic 131-I whole body scan revealed the presence of residual thyroid tissue in all cases. All patients received one or more courses of radioiodine therapy, for a total of 468 courses. One hundred and twenty-nine out of 249 patients (51.8%) were successfully ablated. The total number of treatment courses needed in these patients was 219. Most patients required multiple doses of radioiodine, only 63 required a single dose. One hundred and twenty patients (48.2%) treated with radioiodine were not ablated and are still under treatment program. The clinical features and the amount of thyroid residue were not different in ablated or not-ablated patients. Our results indicate that in this particular population of post-Chernobyl thyroid carcinomas, thyroid ablation is a rather difficult task. Only 51.8% were successfully ablated. Possible explanation for this finding may be the young age of the patients, other particular features of post-Chernobyl thyroid carcinoma or technical aspects, such as less radical surgical procedures.     

Radioiodine in the treatment of medullary carcinoma of the thyroid.

Medullary carcinoma (MC) of the thyroid, in contrast to papillary-follicular carcinoma, fails to concentrate iodine and thus has not been treated with radioactive iodine. We have successfully treated a 16-yr-old Mexican-American girl with residual MC after maximal thyroidectomy (Tx), utilizing radioiodine (131I) to deliver radiation to residual follicular cells in the tumor bed. Immediately after Tx, plasma thyrocalcitonin levels before and during calcium infusion were all elevated (640--1200 pg/ml). 131I (150 mCi) was administered 12 days after Tx after four daily im injections of bovine TSH. Three months after 131I therapy, thyrocalcitonin levels before and during calcium infusion were all normal (less than 50 pg/ml). Ten months after 131I therapy, thyrocalcitonin levels before and after iv pentagastrin were all normal (less than 60 pg/ml). These results suggest that parafollicular cells are radiosensitive, and that therapeutic levels of radiation can be delivered to these cells after Tx if iodine trapping by the remaining follicular cells is enhanced by high levels of circulating TSH. 131I may be the therapy of choice for MC after Tx, if disease has not spread beyond the area proximate to the thyroid gland.     

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

OBJECTIVE: 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. DESIGN: 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. PATIENTS: Sixty papillary thyroid carcinoma patients with elevated thyroglobulinaemia but negative DxWBS were included. Twenty-eight patients were treated, and 32 were untreated. MEASUREMENTS: 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. RESULTS: 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%). CONCLUSIONS: 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.     

Local reactions to radioiodine in the treatment of thyroid cancer

PURPOSE: To compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration. PATIENTS AND METHODS: We retrospectively studied 59 patients who had received 131I between 1979 and 1989. The patients were divided into two groups, depending on the extent of their previous surgical thyroid excision. Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive thyroid excision (near-total or subtotal thyroidectomy) before the radioiodine treatment. RESULTS: Sixty percent of the 10 patients in Group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid. In one case, the local reaction was very severe and accompanied by the development of transient hyperthyroidism. There was only a 6% local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy (p less than 0.001), and none had a severe reaction. CONCLUSIONS: Patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation. If radioiodine is to be employed in such patients, they should be informed of this possible complication. Since evidence supports a dose effect in the pathogenesis of the complications, we recommend using a dose of less than 30 mCi for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation.     

Radioiodine dosimetry in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis therapy

In patients with end-stage renal disease (ESRD), Na131I dosages for thyroid cancer may have to be reduced to avoid excess radiation doses to red marrow, because radioiodine is primarily excreted by kidneys. In ESRD patients receiving continuous ambulatory peritoneal dialysis (CAPD) therapy (three to five 2-L exchanges daily) creatinine clearance rates are very low (mean, 7 mL/min), and radioiodine clearance rates may be proportionately reduced. Thus, radioiodine kinetic studies were performed in two hypothyroid CAPD patients with thyroid cancer, in eight euthyroid CAPD patients, and in eight thyroid cancer patients with normal renal function. All received Na131I or Na123I orally, with serial blood, urine, and/or dialysate sampling for 24-70 h. Dosimetry calculations were performed using the MIRDOSE3 computer program. In CAPD patients, serum radioiodine half-times were 5 times longer, and radioiodine clearance rates by urine plus dialysate were 20% of those in patients with normal renal function. Na131I dosages for the two CAPD patients with thyroid cancer were reduced from 150 mCi [5.6 gigabecquerels (GBq)] to 26.6 mCi (0.98 GBq) and 29.9 mCi (1.11 GBq), respectively, resulting in radiation doses to red marrow and total body comparable to those in patients with normal renal function who received a mean of 148 mCi (5.5 GBq) Na131I. Thus, in patients receiving continuous ambulatory peritoneal dialysis therapy, 5-fold reductions in radioiodine clearance rates require 5-fold decreases in Na131I dosages to avoid excessive radiation doses to total body and red marrow.     

Are there disadvantages in administering 131I ablation therapy in patients with differentiated thyroid carcinoma without a preablative diagnostic 131I whole‐body scan?

OBJECTIVE: To evaluate the risk of performing inappropriate (131)I ablative therapies for thyroid carcinoma in patients lacking thyroid remnants or metastases, using a strategy of treatment without a preliminary iodine-131 diagnostic whole-body scan (DxWBS). DESIGN: Retrospective evaluation of post-therapy whole-body scans to assess the prevalence of thyroid remnants or metastases after total thyroidectomy. Comparison of (131)I uptake test and thyroglobulin (Tg) off levothyroxine (L-T4) performed before therapy with post-therapy scans, in order to evaluate the ability to predict inappropriate treatments. PATIENTS: A group of 875 consecutive patients with previous total or near-total thyroidectomy for differentiated thyroid carcinoma underwent (131)I ablative therapy without a preliminary (131)I-DxWBS. All patients were clinically free of distant metastases and macroscopic residual tumour. MEASUREMENTS: Whole-body scans were performed 2-5 days after the treatment as gold standard for thyroid remnants and metastases; 24-h (131)I quantitative neck uptake test and Tg off L-T4 were performed before (131)I therapy. RESULTS: The majority of patients (94%) were found to have thyroid remnants or metastases at post-therapy scans, in most cases (91.2%) with detectable Tg off L-T4 and positive 24-h neck uptake. 14 patients (1.6%) with tiny lymph-node metastases positive at post-therapy scans showed undetectable Tg off L-T4. In 30 patients (3.6%) faint positive post-therapy images for thyroid remnants have been classified as false-positive results on the basis of both negative 24-h neck uptake and undetectable Tg off L-T4. CONCLUSIONS: This study confirms that most patients have residual thyroid tissue after total thyroidectomy and that it seems reasonable to omit routine diagnostic whole-body scans before (131)I treatment with clinical, managerial and economic advantages.     

Poorly differentiated thyroid carcinomas: new therapeutic considerations

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.     

Thyroglobulin measurement before rhTSH-aided 131I ablation in detecting metastases from differentiated thyroid carcinoma

Aim Thyroidectomy followed by administration of large activities of 131‐iodine (¹³¹I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4‐Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for pre‐ablative offT4‐Tg when recombinant human TSH (rhTSH) is used as stimulus before treatment. The present study was undertaken to evaluate if post‐thyroidectomy Tg values, measured before rhTSH‐stimulated radioiodine ablation is of prognostic value in patients affected by DTC. Methods We enrolled 126 patients with DTC submitted to total thyroidectomy. T4 treatment was started just after surgery to suppress TSH levels and Tg levels (onT4‐Tg) were measured just before rhTSH‐aided thyroid ablation by ¹³¹I (3700 MBq). Neck radioiodine uptake (RAIU) was measured just before ablation and a post‐treatment whole body scan (PT‐WBS) was performed. Results A significant relationship was found between thyroid remnants’ RAIU and onT4‐Tg levels (P < 0·001). The 1·10 ng/ml onT4‐Tg threshold selected by ROC curve analysis identifies patients with positive PT‐WBS with 83·3% sensitivity, 65·7% specificity, 44·5% positive predictive value (PPV) and 93·6% negative predictive value (NPV). The 0·65 ng/ml cut‐off level recognizes metastatic patients with 82·9% sensitivity, 55·2% specificity, 43·3% PPV and 97·8% NPV when compared with 12 months restaging results. Among 63 patients with initially undetectable onT4‐Tg (i.e. ≤ 0·2 ng/ml) none had positive PT‐WBS nor DTC relapse at 12‐month restaging (NPV 100%). Conclusions Based on our data we conclude that pre‐ablative onT4‐Tg is a prognostic marker and should be used instead of pre‐ablative TSH‐stimulated Tg measurement when rhTSH‐aided radioiodine ablation is done.     

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma

OBJECTIVES: In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. PATIENTS: We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. RESULTS: The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. CONCLUSIONS: With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.