This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pacini, F. Articles by Pinchera, A. Search for Related Content PubMed PubMed Citation Articles by Pacini, F. Articles by Pinchera, A.

Ablation of Thyroid Residues with 30 mCi ¹³¹I: A Comparison in Thyroid Cancer Patients Prepared with Recombinant Human TSH or Thyroid Hormone Withdrawal

Department of Endocrinology and Metabolism, University of Pisa, 56124 Pisa, Italy

Address all correspondence and requests for reprints to: F. Pacini, M.D., Department of Endocrinology, Via Paradisa, 2, 56124 Pisa, Italy.

Abstract

The aim of the study was to assess whether stimulation by recombinant human TSH (rhTSH) may be used in patients with differentiated thyroid carcinoma for postsurgical ablation of thyroid remnants using a 30-mCi standard dose of ¹³¹I during thyroid hormone therapy. The rate of ablation was prospectively compared in three groups of patients consecutively assigned to one of three treatment arms: in the first arm, patients (n = 50) were treated while hypothyroid (HYPO); in the second arm, patients (n = 42) were treated while HYPO and stimulated in addition with rhTSH (HYPO + rhTSH); in the third arm, patients (n = 70) were treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH (EU + rhTSH). The outcome of thyroid ablation was assessed by conventional HYPO ¹³¹I scan performed in HYPO state 6–10 months after ablation.

Basal serum TSH was elevated in the HYPO and HYPO + rhTSH groups. In the EU + rhTSH group, basal serum TSH was 1.3 ± 2.5 µU/ml (range, <0.005–11.9 µU/ml). After rhTSH, serum TSH significantly increased in the HYPO + rhTSH group and the EU + rhTSH group.

Basal 24-h radioiodine thyroid bed uptake was 5.8 ± 5.7% (range, 0.2–21%) and 5.4 ± 5.7% (range, 0.2–26%) in the HYPO and HYPO + rhTSH groups, respectively. In the HYPO + rhTSH group, mean 24-h thyroid bed uptake rose to 9.4 ± 9.5% (range, 0.2–46%) after rhTSH (P < 0.0001). The 24-h uptake after rhTSH in the EU + rhTSH group was 2.5 ± 4.3% (range, 0.1–32%), significantly lower (P < 0.0001) than that found in the HYPO and HYPO + rhTSH groups.

The rate of successful ablation was similar in the HYPO and HYPO + rhTSH groups (84% and 78.5%, respectively). A significantly lower rate of ablation (54%) was achieved in the EU + rhTSH group.

Mean initial dose rate (the radiation dose delivered during the first hour after treatment) was significantly lower in the EU + rhTSH group (10.7 ± 12.6 Gy/h) compared with the HYPO + rhTSH group (48.5 ± 43 Gy/h) and the HYPO group (27.1 ± 42.5 Gy/h).

In conclusion, our study indicates that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is not sufficient for a satisfactory thyroid ablation rate. Possible reasons for this failure may be the low 24-h radioiodine uptake, the low initial dose rate delivered to the residues, and the accelerated iodine clearance observed in EU patients. Possible alternatives for obtaining a satisfactory rate of thyroid ablation with rhTSH may consist of increasing the dose of radioiodine or using different protocols of rhTSH administration producing more prolonged thyroid cells stimulation.

RADIOIODINE-¹³¹ HAS BEEN USED for many years to ablate thyroid residues after thyroidectomy for differentiated thyroid carcinoma. Delivery of radioiodine to thyroid residues requires stimulation by high levels of endogenous TSH, achieved by inducing an adequate period of hypothyroidism after withdrawal of thyroid hormone medication.

The optimal dose of ¹³¹I necessary for successful ablation is not established. A few authors use a dosimetric approach to define the theoretical ablative dose (1, 2, 3), whereas most centers prefer to give a standard dose, which may range from as low as 30 mCi to as high as 100 mCi or more. When using low doses of radioiodine (30–50 mCi), several authors have reported ablation rates greater than 70–80%, similar to those achieved with higher doses (4, 5, 6, 7). For several years, we have been using 30 mCi of ¹³¹I for routine ablation of thyroid residues based on the possibility to use this dose on an outpatient basis. In our hands, the rate of successful ablation with such a protocol is nearly 80%.

Recently, stimulation by exogenous recombinant human TSH (rhTSH; Thyrogen, Genzyme Corp., Cambridge, MA) has been introduced in the clinical practice as an effective alternative to thyroid hormone withdrawal in the diagnostic follow-up of patients treated for differentiated thyroid cancer (8, 9, 10, 11) and in the radioiodine treatment of metastatic patients at risk of morbidity if withdrawn from thyroid hormones (12, 13). The advantage of using rhTSH is the avoidance of the signs and symptoms of hypothyroidism, with the obvious consequence of a better quality of life for the patients (14).

The aim of the present study was to assess whether stimulation by rhTSH could be used for thyroid ablation of postsurgical thyroid remnants using a 30-mCi standard dose of ¹³¹I during thyroid hormone therapy. The study was prospective and included a control group of patients treated with a similar dose of radioiodine while hypothyroid (HYPO), a second group treated while HYPO with the addition of rhTSH stimulation, and a third group treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH. The final end point was to compare the rate of successful ablation in these three groups, as assessed by control HYPO ¹³¹I scan, performed 6–10 months later.

Patients and Methods

Study design

The study was designed to compare the rate of successful ablation of postsurgical thyroid residues with a 30-mCi standard dose of ¹³¹I. Patients were assigned to one of three arms: in the first arm, patients were treated while HYPO; in the second arm, patients were treated while HYPO and stimulated in addition with rhTSH (HYPO + rhTSH); in the third arm, patients were treated while EU on L-T₄ therapy and stimulated with rhTSH (EU + rhTSH). Patients willing to enter this clinical trial (after signed informed consent) were recruited from those scheduled for postsurgical thyroid ablation with ¹³¹I. Exclusion criteria were the presence of distant metastases at diagnosis and less than near-total thyroidectomy as initial treatment. The first 50 consecutive patients were entered in the HYPO group, the second 50 in the HYPO + rhTSH group, and the following 75 in the EU + rhTSH group.

A schematic flowchart of the study protocol is reported in Table 1. In the HYPO arm, patients were rendered HYPO by withdrawal of L-T₄ therapy 45 d before ablation and of L-T₃ 15 d before ablation. At d 1 of the study, blood samples for serum TSH, free T₄, free T₃, thyroglobulin (Tg) autoantibodies, and Tg were obtained in all patients. Thereafter, a tracer dose of 50 µCi ¹³¹I was administered, and the 24-h uptake in the thyroid bed was measured using a thyroid uptake system (New Atomlab 950, Biodex Medical Systems, Urbino, Italy). Immediately afterward, the 30-mCi therapeutic dose of ¹³¹I was administered; a post-therapy whole body scan (WBS) was obtained 3–7 d later, depending on the uptake. In the HYPO + rhTSH arm, the protocol for induction of hypothyroidism and thyroid uptake was the same as in the HYPO group. In addition, after the basal 24-h uptake, patients received an injection of 0.9 mg rhTSH (Thyrogen) for 2 consecutive days, and a second 24-h thyroid bed uptake with 50 µCi ¹³¹I tracer dose was obtained. Serum Tg and TSH were also measured after exogenous TSH stimulation. The therapeutic ¹³¹I dose was delivered 48 h after the last injection of rhTSH, and a post-therapy scan was obtained as in the previous arm. In the EU + rhTSH arm, patients were maintained on L-T₄ therapy. At d 1 and 2, after blood drawing, patients were injected with 0.9 mg rhTSH, followed by 24-h thyroid bed uptake with 50 µCi ¹³¹I tracer dose. Also in this group, the therapeutic dose of radioiodine was administered 48 h after the last injection of rhTSH, followed by a post-therapy WBS.

To rule out contamination by stable iodine, urinary iodine excretion was measured in all patients before ¹³¹I administration for ablation and before performing the follow-up scan. No patient had urinary iodine excretion greater than the upper limit of normal range in our laboratory (200 µg/liter).

Patients

The study was completed by 50 of 50 patients in the HYPO group, 42 of 50 patients in the HYPO + rhTSH group, and 70 of 75 patients in the EU + rhTSH group. Reasons for withdrawal from the study were presence of unsuspected distant metastases in the post-therapy WBS in five patients and impossibility to perform the control diagnostic WBS in due time in eight patients. The clinical-epidemiological features of the patients are reported in Table 2. No significant difference was observed among the three arms in regard to age, sex, histotype, and tumor-node-metastases classification.

The dimension of thyroid residues was evaluated by neck ultrasound, using a color Doppler apparatus (AU 590 Asynchronous, Esaote Biomedica, Firenze, Italy) with a 7.5-MHz linear transducer. The three diameters of thyroid residues on both sides were measured, and the total amount was calculated according to the formula of the ellipsoid model (width x length x thickness x 0.52 for each lobe) as previously reported (15). This formula has been specifically validated for the measurement of postsurgical thyroid remnants (16). The total volume (in milliliters) obtained was converted into grams, assuming 1 ml equal to 1 g.

Assessment of initial dose rate (IDR)

The IDR was calculated as reported by Samuel and Rajashekharrao (17). Briefly, IDR was obtained according to the following formula: IDR (Gy/h) = 0.11 x MBq of ¹³¹I/g of tissue, where MBq/g were obtained by dividing the total MBq of ¹³¹I taken up (as assessed by the 24-h percentage uptake) by the mass of the thyroid residue expressed in grams. This measurement gives an idea of the amount of radiation delivered in the first hour and has been validated as an important parameter of ablation response (17). At variance with the study by Samuel and Rajashekharrao (17), who used the rectilinear images to assess the volume of the thyroid residue, we used the thyroid volume derived from neck ultrasound. Although no study has addressed the correspondence between thyroid residues measured by scan and by ultrasound, it is likely that both procedures give similar results, as shown in a comparison by Wesche et al. (18) in patients undergoing ¹³¹I therapy for hyperthyroidism. The cumulative radiation dose, another important parameter of radiation dose calculated by also taking into account the effective half-life of ¹³¹I, could not be assessed in the present study, due to the lack of measurements of the effective half-life.

Statistical analysis

The Mann-Whitney U test and Kruskal-Wallis test were used for the statistical analysis of differences among different groups, and the Wilcoxon signed rank test was used for paired analysis within the same group. The t test was used for the statistical analysis of differences between TSH levels after log-transformation of TSH values. The ² test was used for the analysis of epidemiological and clinical features of different groups. A P value less than 0.05 was considered significant.

Results

Basal and rhTSH-stimulated serum TSH and 24-h uptake

As shown in Fig. 1, serum TSH was elevated in the HYPO (63.2 ± 19.6 µU/ml; range, 19–100 µU/ml) and HYPO + rhTSH (71.0 ± 35.9 µU/ml; range, 14.7–144 µU/ml) groups with no significant difference. In the EU + rhTSH group, basal serum TSH was 1.3 ± 2.5 µU/ml (range, <0.005–11.9 µU/ml), significantly lower with respect to the TSH of the two HYPO groups (P < 0.0001 by Mann-Whitney U test and Kruskal-Wallis test), with 24 of 70 patients having levels below 0.1 µU/ml. After rhTSH, serum TSH peaked to 281 ± 97 µU/ml (range, 124–582 µU/ml) in the HYPO + rhTSH group and to 126 ± 44.8 µU/ml (range, 42–219 µU/ml) in the EU + rhTSH group. In both groups, the increase of serum TSH was statistically significant with respect to basal levels (P < 0.0001 by Wilcoxon test for paired data and by t test for paired data after log-transformation of TSH values).

View larger version (16K): [in this window] [in a new window]   Figure 1. Serum TSH in the three groups of patients: HYPO, HYPO + rhTSH, and EU + rhTSH. Rectangular boxes represent the TSH range, and symbols inside boxes represent the mean ± SD.

View larger version (12K): [in this window] [in a new window]   Figure 2. Twenty-four hour thyroid bed 131-I uptake in the three groups of patients: HYPO, HYPO + rhTSH, and EU + rhTSH. The horizontal bars represent the mean.

Results of post-therapy WBS

The post-therapy WBS after 30 mCi of ¹³¹I showed the presence of significant thyroid bed uptake in all patients. Additional areas of iodine uptake in regional lymph node metastases were present in three patients, one in each arm. Distant metastases were never observed.

Outcome of thyroid ablation as assessed by diagnostic ¹³¹I WBS

Six to 10 months after ablation, all patients underwent a diagnostic ¹³¹I WBS with a tracer dose of 4 mCi in hypothyroid status. The rate of successful ablation in the three arms is shown in Fig. 3. In the HYPO and HYPO + rhTSH groups, the rate of successful ablation was similar, 84% and 78.5%, respectively. A significantly lower rate of ablation (54%) was achieved in the EU + rhTSH group (P < 0.0001 and P < 0.01, respectively). Pathological areas of uptake outside the thyroid bed (regional lymph nodes) were observed in three patients (all not ablated) of the EU + rhTSH group.

View larger version (12K): [in this window] [in a new window]   Figure 3. Percentage of successful ablation in HYPO, HYPO + rhTSH, and EU + rhTSH patients, as assessed by conventional HYPO 131I scan performed in HYPO state, 6–10 months after ablation.

Assessment of IDR delivered to thyroid residues and correlation with ablation rate

As shown in Table 3, the estimated mass of thyroid residue was not different in the three groups of patients. The mean IDR delivered with 30 mCi of ¹³¹I therapy was 48.5 ± 43 Gy/h in the HYPO + rhTSH group, significantly higher than that delivered to the HYPO group (27.1 ± 42.5 Gy/h; P = 0.007) and the EU + rhTSH group (10.7 ± 12.6 Gy/h; P < 0.0001 by Mann-Whitney U test and Kruskal-Wallis test). A significant difference of IDR (P = 0.01) was also found between the HYPO and the EU + rhTSH groups.

View larger version (16K): [in this window] [in a new window]   Figure 4. IDR expressed as Gy/h in ablated and not ablated patients. The horizontal bars indicate mean + SD.

Although the optimal dose of ¹³¹I necessary to achieve thyroid remnant ablation is controversial, several studies have shown that a standard dose of 30 mCi may be effective when given in the HYPO state (4, 5, 6, 7). In the past, we have used 30 mCi of radioiodine as the standard ablative dose, obtaining a rate of ablation of about 80% (our unpublished observation). On the basis of this evidence, a radioiodine dose of 30 mCi was also chosen in the present randomized study, aimed to assess the efficacy of rhTSH-stimulated thyroid ablation.

We chose to randomize by three consecutive blocks of patients. This strategy is probably not conventional. The reason for this choice was merely practical: to have many patients performing three different protocols in the same period might be fraught with mistakes and difficult to manage. Likely, we did not introduced any bias, because patients were all consecutive and because no patients refused inclusion in the study. Furthermore, the readers of the follow-up scans were not biased by knowledge of the provenience of the patients, because they were all hypothyroid and did not come in the same order in which they performed the ablation study, but were diluted in a 6- to 10-month period, thus overlapping.

The rate of successful ablation in the HYPO group was very much in keeping with that expected (higher than 80%). The addition of rhTSH to hypothyroidism did not increase the rate of successful ablation, despite a significant increase of serum TSH and of 24-h radioiodine uptake, resulting also in a significantly higher initial radiation dose to the thyroid remnant. The reason for this finding is not apparent. Previous experience with the combination of endogenous and exogenous TSH stimulation is available in a single study by Siddiqui et al. (19), who found a very low rate of thyroid ablation when treating HYPO patients with 30 mCi after bovine TSH stimulation.

In the group of patients treated with radioiodine under rhTSH stimulation while continuing their thyroid hormone therapy, the 24-h radioiodine uptake was significantly lower than that of HYPO patients. Thyroid ablation was obtained in 54% of them. This result, although comparable to the rate of ablation found in some series of HYPO patients treated with low ¹³¹I doses (20, 21, 22, 23), is disappointing when compared with the ablation rate obtained in the HYPO patients of our study.

As pointed out by Maxon et al. (1, 2), quantitative radiation dosimetry is of paramount importance in assessing the effective ablative dose to be delivered to thyroid cancer patients. According to these authors, ablation of thyroid residues is usually achieved when delivering at least 300 Gy. Two measures of radiation dose may be applied to patients treated with radioiodine: the cumulative absorbed dose and the initial radiation dose. We could not assess the cumulative radiation dose, which probably better reflects the true effect of radioactive therapy, but we calculated the IDR. Unfortunately, this measurement has been reported as a good predictor of radioiodine effect only in one study (17), and thus it is not fully validated. According to this parameter, rhTSH-treated EU patients had the lowest IDR, as a consequence of their lower uptake. Similarly, low 24-h radioiodine uptakes were found by Robbins et al. (24) in 10 patients submitted to thyroid ablation with rhTSH. At variance with our results, these authors achieved total ablation in all patients; however, they used much higher doses of ¹³¹I (110 mCi as a mean), and the diagnostic ¹³¹I WBS to control for thyroid ablation was performed with rhTSH. Increasing the dose of radioiodine would probably increase the IDR above a threshold that in our study was always associated with successful ablation (i.e. 50 Gy/h).

In the present study, the ablative dose was administered 48 h after the last injection of rhTSH, 24 h later with respect to previous studies using rhTSH for diagnostic or therapeutic purposes (9, 12). This change was motivated by the need to have the 24-h uptake study with 50 µCi in the rhTSH groups with the same modality of the HYPO group. When planning the study, we realized that this modification might affect the outcome of thyroid ablation. Serum TSH in the EU group was lower at 48 h with respect to 24 h after the last injection of rhTSH. However, even at 48 h, serum TSH was still elevated and only slightly lower with respect to that of the HYPO group, and thus theoretically sufficient to promote adequate radioiodine uptake for ablation. Furthermore, it is possible that the most important factor in determining the uptake of follicular thyroid cells is not just the high level of TSH on the day of the radioiodine administration, but rather the total period of time in which TSH was sufficiently elevated to stimulate the machinery of the cells. Of course, we have no proof for that, but to support our hypothesis we would like to mention a report by Kogai et al. (25) showing that in vitro, the mRNA of the NIS gene started increasing 3–6 h after administration of rhTSH, but the NIS protein started to increase only after 36 h and peaked at 72 h after the administration. If this data may be applied in vivo, it is possible that the concentration of the NIS protein was higher in our patients treated 48 h after the last injection of rhTSH compared with patients treated after 24 h, as prescribed in the standard protocol of Thyrogen administration.

Another important issue to be considered is the metabolic state of the patients, EU vs. HYPO. As usually assumed and recently reported by Park et al. (26), the clearance rate of ¹³¹I is decreased, and its bioavailability increased in HYPO patients, resulting in an increase of the cumulative absorbed dose in the thyroid residues. On the contrary, EU patients have a normal iodine clearance, resulting in lower cumulative absorbed doses. On this assumption, patients treated with radioiodine therapy for metastatic disease using rhTSH have been given higher doses of radioiodine compared with the conventional doses used in the HYPO state (12, 13). Furthermore, the exogenous stimulation provided by rhTSH is acute and short-lasting (high levels of serum TSH are observed during 4–5 d after injection). Also, this fact may contribute to a low level of reuptake of circulating radioiodine in the days following the administration of the therapeutic dose.

According to other authors (1, 24), successful thyroid ablation was defined as the absence of visual uptake in the scan. Another way of defining successful ablation might be the finding of negative scan or undetectable serum Tg off L-T₄, regardless of visible thyroid bed uptake at scan. Applying this definition to our study, we would end up with a rate of ablation in the EU + rhTSH group of 74.1%, much higher than that defined by visual uptake (54%) and fully satisfactory considering that the therapeutic dose was only 30 mCi. We add this notice just as a perspective and provocative item, although our conclusion is based on the results of visual thyroid bed uptake.

In conclusion, our study indicates that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is not sufficient for a satisfactory thyroid ablation rate. All together, the possible reasons for this failure may be the low 24-h radioiodine uptake, the low IDR, and the accelerated iodine clearance observed in EU patients. Possible alternatives for obtaining a satisfactory rate of thyroid ablation with rhTSH may consist of increasing the dose of radioiodine or using different protocols of rhTSH administration producing more prolonged thyroid cell stimulation.

Acknowledgments

Footnotes

This work was supported in part by grants from Associazione Italiana Ricerca sul Cancro; European Communities INCO-Copernicus projects IC-15-CT-980314; and Ministero dell’Università e della Ricerca Scientifica e Tecnologica 2000. M.C.G. is a fellow from the Clinical and Experimental Department of Medicine and Pharmacology, University of Messina, Italy. L.A. is the recipient of a fellowship from Federazione Italiana Ricerca sul Cancro.

Abbreviations: EU, Euthyroid; EU + rhTSH, euthyroid and stimulated with rhTSH; HYPO, hypothyroid; HYPO + rhTSH, hypothyroid and stimulated with rhTSH; IDR, initial dose rate; ns, not significant; rhTSH, recombinant human TSH; Tg, thyroglobulin; WBS, whole body scan.

Received December 4, 2001.

Accepted May 21, 2002.

References

1. Maxon 3rd HR, Englaro EE, Thomas S, Hertzberg VS, Hinnefeld JD, Chen LS, Smith H, Cummings D, Aden MD 1992 Radioiodine-131 therapy for well-differentiated thyroid cancer—a quantitative radiation dosimetric approach: outcome and validation in 85 patients. J Nucl Med 33:1132–1136[Abstract/Free Full Text]
2. Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL 1983 Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med 309:937–941[Abstract]
3. Hadjieva T 1986 Quantitative approach to radioiodine ablation of thyroid remnants following surgery for thyroid cancer. Radiobiol Radiother 26:819–824
4. McCowen KD, Adler RA, Ghaed N, Verdon T, Hofeldt FD 1976 Low dose radioiodine thyroid ablation in postsurgical patients with thyroid cancer. Am J Med 61:52–58[CrossRef][Medline]
5. Mazzaferri E 1997 Thyroid remnant 131-I ablation for papillary and follicular thyroid carcinoma. Thyroid 7:265–271[Medline]
6. Johansen K, Woodhouse NJY, Odugbesan O 1991 Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer. J Nucl Med 32:252–254[Abstract/Free Full Text]
7. DeGroot L, Reilly M 1982 Comparison of 30 and 50 mCi doses of iodine-131 for thyroid ablation. Ann Intern Med 96:51–53
8. Ladenson PW, Braverman LE, Mazzaferri EL, Brucker-Davis F, Cooper DS, Garber JR, Wondisford FE, Davies TF, DeGroot LJ, Daniels GH, Ross DS, Weintraub BD 1997 Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med 337:888–896[Abstract/Free Full Text]
9. Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon 3rd HR, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC 1999 A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 84:3877–3885[Abstract/Free Full Text]
10. Robbins RJ, Tuttle RM, Sharaf RN, Larson SM, Robbins HK, Ghossein RA, Smith A, Drucker WD 2001 Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma. J Clin Endocrinol Metab 86:619–625[Abstract/Free Full Text]
11. David A, Blotta A, Bondanelli M, Rossi R, Roti E, Braverman LE, Busutti L, degli Uberti EC 2001 Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone. J Nucl Med 42:1470–1475[Abstract/Free Full Text]
12. Lippi F, Capezzone M, Angelini F, Taddei D, Molinaro E, Pinchera A, Pacini F 2001 Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH. Eur J Endocrinol 144:5–11[Abstract]
13. Luster M, Lassmann M, Haenscheid H, Michalowski U, Incerti C, Reiners C 2000 Use of recombinant human thyrotropin before radioiodine therapy in patients with advanced differentiated thyroid carcinoma. J Clin Endocrinol Metab 85:3640–3645[Abstract/Free Full Text]
14. Dow K, Ferrel B, Anello C 1997 Quality-of-life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy. Thyroid 7:613–619[Medline]
15. Vitti P, Martino E, Aghini-Lombardi F, Rago T, Antonangeli L, Maccherini D, Nanni P, Loviselli A, Balestrieri A, Araneo G 1994 Thyroid volume measurement by ultrasound in children as a tool for the assessment of mild iodine deficiency. J Clin Endocrinol Metab 79:600–603[Abstract]
16. Arslan N, Ilgan S, Serdengecti M, Ozguven MA, Bayhan H, Okuyucu K, Gulec SA 2001 Post-surgical ablation of thyroid remnants with high-dose ¹³¹I in patients with differentiated thyroid carcinoma. Nucl Med Commun 22:1021–1027[CrossRef][Medline]
17. Samuel AM, Rajashekharrao B 1994 Radioiodine therapy for well-differentiated thyroid cancer: a quantitative dosimetric evaluation for remnant thyroid ablation after surgery. J Nucl Med 35:1944–1950[Abstract/Free Full Text]
18. Wesche M, Tiel-van Buul MM, Smits NJ, Wiersinga WM 1998 Ultrasonographic versus scintigraphic measurement of thyroid volume in patients referred for ¹³¹I therapy. Nucl Med Commun 19:341–346[Medline]
19. Siddiqui A, Edmondson J, Wellman HN, Hamaker RC, Lingeman RE, Park HM, Johnston CC 1981 Feasibility of low doses of I-131 for thyroid ablation in postsurgical patients with thyroid carcinoma. Clin Nucl Med 6:158–161[CrossRef][Medline]
20. Ramanna L, Waxman AD, Brachman MB, Tanasescu DE, Sensel N, Braunstein GD 1985 Evaluation of low-dose radioiodine ablation therapy in postsurgical thyroid cancer patients. Clin Nucl Med 10:791–795[CrossRef][Medline]
21. Ramacciotti C, Pretorius HT, Line BR, Goldman JM, Robbins J 1982 Ablation of nonmalignant thyroid remnant with low dose of radioactive iodine: concise communication. J Nucl Med 23:483–489[Abstract/Free Full Text]
22. Snyder J, Gorman C, Scanlon P 1983 Thyroid remnant ablation: questionable pursuit of an III-defined goal. J Nucl Med 24:659–665[Abstract/Free Full Text]
23. Comtois R, Thériault C, Del Vecchio P 1993 Assessment of the efficacy of iodine-131 for thyroid ablation. J Nucl Med 34:1927–1930[Abstract/Free Full Text]
24. Robbins RJ, Tuttle RM, Sonenberg M, Shaha A, Sharaf R, Robbins H, Fleisher M, Larson SM 2001 Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin. Thyroid 11:865–569[CrossRef][Medline]
25. Kogai T, Endo T, Saito T, Miyazaki A, Kawaguchi A, Onaya T 1997 Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells. Endocrinology 138:2227–2232[Abstract/Free Full Text]
26. Park SG, Reynolds JC, Brucker-Davis F, Whatley M, McEllin K, Maxted D, Robbins J, Weintraub BD 1996 Iodine kinetics during 131-I scanning in patients with thyroid cancer: comparison of studies with recombinant human TSH (rhTSH) vs hypothyroidism. J Nucl Med 37:15p–15p

This article has been cited by other articles:

				R. M. Tuttle, M. Brokhin, G. Omry, A. J. Martorella, S. M. Larson, R. K. Grewal, M. Fleisher, and R. J. Robbins Recombinant Human TSH-Assisted Radioactive Iodine Remnant Ablation Achieves Short-Term Clinical Recurrence Rates Similar to Those of Traditional Thyroid Hormone Withdrawal J. Nucl. Med., May 1, 2008; 49(5): 764 - 770. [Abstract] [Full Text] [PDF]

				T. Pilli, E. Brianzoni, F. Capoccetti, M. G. Castagna, S. Fattori, A. Poggiu, G. Rossi, F. Ferretti, E. Guarino, L. Burroni, et al. A Comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-Iodine Administered Doses for Recombinant Thyrotropin-Stimulated Postoperative Thyroid Remnant Ablation in Differentiated Thyroid Cancer J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3542 - 3546. [Abstract] [Full Text] [PDF]

				A. Hackshaw, C. Harmer, U. Mallick, M. Haq, and J. A. Franklyn 131I Activity for Remnant Ablation in Patients with Differentiated Thyroid Cancer: A Systematic Review J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 28 - 38. [Abstract] [Full Text] [PDF]

				H. Hanscheid, M. Lassmann, M. Luster, S. R. Thomas, F. Pacini, C. Ceccarelli, P. W. Ladenson, R. L. Wahl, M. Schlumberger, M. Ricard, et al. Iodine Biokinetics and Dosimetry in Radioiodine Therapy of Thyroid Cancer: Procedures and Results of a Prospective International Controlled Study of Ablation After rhTSH or Hormone Withdrawal J. Nucl. Med., April 1, 2006; 47(4): 648 - 654. [Abstract] [Full Text] [PDF]

				F. Pacini, P. W. Ladenson, M. Schlumberger, A. Driedger, M. Luster, R. T. Kloos, S. Sherman, B. Haugen, C. Corone, E. Molinaro, et al. Radioiodine Ablation of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma: Results of an International, Randomized, Controlled Study J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 926 - 932. [Abstract] [Full Text] [PDF]

				S. Pena, S. Arum, M. Cross, B. Magnani, E. N. Pearce, M. E. Oates, and L. E. Braverman 123I Thyroid Uptake and Thyroid Size at 24, 48, and 72 Hours after the Administration of Recombinant Human Thyroid-Stimulating Hormone to Normal Volunteers J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 506 - 510. [Abstract] [Full Text] [PDF]

				B Jarzab, D Handkiewicz-Junak, and J Wloch Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review Endocr. Relat. Cancer, December 1, 2005; 12(4): 773 - 803. [Abstract] [Full Text] [PDF]

				F. Pacini, M. Schlumberger, C. Harmer, G. G Berg, O. Cohen, L. Duntas, F. Jamar, B. Jarzab, E. Limbert, P. Lind, et al. Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report Eur. J. Endocrinol., November 1, 2005; 153(5): 651 - 659. [Abstract] [Full Text] [PDF]

				M. G. Castagna, A. Pinchera, A. Marsili, M. Giannetti, E. Molinaro, P. Fierabracci, L. Grasso, F. Pacini, F. Santini, and R. Elisei Influence of Human Body Composition on Serum Peak Thyrotropin (TSH) after Recombinant Human TSH Administration in Patients with Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4047 - 4050. [Abstract] [Full Text] [PDF]

				M. Luster, F. Lippi, B. Jarzab, P. Perros, M. Lassmann, C. Reiners, and F. Pacini rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review Endocr. Relat. Cancer, March 1, 2005; 12(1): 49 - 64. [Abstract] [Full Text] [PDF]

				C. S. Bal, A. Kumar, and G. S. Pant Radioiodine Dose for Remnant Ablation in Differentiated Thyroid Carcinoma: A Randomized Clinical Trial in 509 Patients J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1666 - 1673. [Abstract] [Full Text] [PDF]

				C. Menzel, F. Grunwald, and H. J. Biersack Monitoring of Low-Risk Patients with Papillary Thyroid Carcinoma J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4507 - 4507. [Full Text] [PDF]

				S. I. Sherman Optimizing the Outcomes of Adjuvant Radioiodine Therapy in Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4059 - 4062. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pacini, F. Articles by Pinchera, A. Search for Related Content PubMed PubMed Citation Articles by Pacini, F. Articles by Pinchera, A.