Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH

OBJECTIVE: This study tested the hypothesis that administration of human recombinant thyroid-stimulating hormone (rhTSH: Thyrogen, thyrotropin alpha) could promote iodine-131 ((131)I) uptake in the therapy for metastatic or locally invasive differentiated thyroid cancer (DTC), obviating L-thyroxine suppressive therapy (L-T4) withdrawal and hypothyroidism in patients with advanced disease. METHODS: Twelve totally (or almost completely) thyroidectomized adults, nine of whom had received earlier therapy after L-T4 withdrawal, underwent (131)I treatment while euthyroid on L-T4, after rhTSH administration. Nine underwent diagnostic whole-body scanning (WBS) after two consecutive daily i.m. injections (0.9 mg) of rhTSH. They then received an identical second course of rhTSH to promote therapeutic (131)I uptake. Post-therapy WBS was performed one week later. Three patients received only rhTSH (131)I therapy. RESULTS: Administration of rhTSH promoted (131)I uptake in all patients, as demonstrated by post-therapy WBS. Administration of rhTSH also promoted a significant increase in serum thyroglobulin (Tg) concentrations. According to the most recent measurements, 3-12 months after therapy, serum Tg levels fell in four, and stabilized in two out of eleven patients. Upon additional rhTSH-WBS 8 months post-study, a reduction in one metastatic site was noted in one patient. The rhTSH was well tolerated, with mild, transient fever and/or nausea occurring in only a minority of patients. Individuals with bone metastases experienced degrees of peritumoral pain and swelling that were similar (though more short-lived) to those seen in the same or other patients after L-T4 withdrawal. CONCLUSIONS: Administration of rhTSH is a safe, successful tool for inducing (131)I uptake in local and metastatic DTC lesions, and avoids L-T4 withdrawal, preserving metabolic homeostasis and preventing the debilitating effects of hypothyroidism.     

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.     

Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment

The follow-up of differentiated thyroid cancer after total thyroidectomy and thyroid ablation is commonly based on serum Tg determination and 131-iodine ((131)I) diagnostic whole-body scan (WBS) performed in the hypothyroid state, 6-12 months after thyroid ablation. Based on the greater sensitivity of Tg measurement, with respect to WBS, the diagnostic yield of diagnostic WBS has been questioned in patients who are off L-T(4) therapy and have undetectable Tg levels. The aim of the present retrospective study was to evaluate the diagnostic relevance of (131)I WBS performed after thyroid remnant ablation, in patients with undetectable serum Tg and off thyroid hormone therapy. The study included 315 of 662 consecutive patients (47.6%) treated in our department between 1980 and 1990, who, at the first control WBS after thyroid ablation, had undetectable serum Tg levels in the hypothyroid state. There were 54 men (17%) and 261 women (83%), with a mean age of 40.9 +/- 13.1 yr (range, 12-76), followed for a mean of 12 +/- 2.8 (range, 9-19) yr. The control WBS was negative in 225 (71.4%) patients and positive for persistent areas of thyroid bed uptake, frequently of very low significance, in 90 (28.6%). No local or distant metastases were discovered. At the last follow-up visit (1999-2000), 281 (89.2%) patients showed complete remission, with undetectable serum Tg off L-T(4) and negative WBS. Persistent thyroid bed uptake, with undetectable levels of Tg, was observed in 29 patients (9.2%) studied during L-T(4) withdrawal. Only 2 patients (0.6%) experienced local recurrence (lymph-node metastases) during their follow-up. In conclusion, our data suggest that the presence of undetectable levels of serum Tg off L-T(4) at the time of the first control WBS after initial treatment, is highly predictive of complete and persistent remission. With the exception of detecting persistent thyroid bed uptake in a minority of cases, the control WBS has never given information that could influence the following therapeutic strategy. On this basis, we propose that the diagnostic (131)I WBS may be avoided in patients with undetectable levels of Tg off L-T(4). These patients may be monitored with clinical examination, neck ultrasound, and serum Tg measurements on L-T(4).     

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.     

The use of recombinant human TSH in the follow-up of differentiated thyroid cancer: experience from a large patient cohort in a single centre

BACKGROUND: Periodic evaluation of serum thyroglobulin (Tg) and whole body 131I imaging (131I-WBS) are essential in the follow-up of differentiated thyroid carcinoma (DTC); both diagnostic modalities require stimulation by high levels of TSH. Administration of recombinant human TSH (rhTSH) is an alternative to the withdrawal of thyroid hormone therapy. OBJECTIVE: The aim of this study was to report our experience in the use of rhTSH for the management of patients with DTC. PATIENTS: One hundred and four patients were enrolled in the study. A dose of 10 U of rhTSH therapy was injected intramuscularly for 2 consecutive days; 24 h after the second dose of rhTSH the patients were administered 4--5 mCi of 131I and, 48 h later, WBS was performed. RESULTS: In all patients, baseline mean serum Tg and TSH levels were 2.4 +/- 1.9 ng/ml and 0.0153 +/- 0.0232 mIU/l, respectively. Basal Tg levels were detectable in 58 out of 104 patients. After rhTSH injection, mean serum TSH levels rose to 122.67 +/- 47.36 mIU/l. Stimulated serum Tg levels increased to greater-than-or-equal 5 ng/ml and the 131I-WBS showed an uptake in 18 patients (17.4%). Among them there were three with bone metastases and one with brain metastases, who reported violent skeletal pain and a severe headache, respectively. These were caused by the growth of tumour mass of metastases induced by rhTSH administration. CONCLUSIONS: The use of rhTSH avoids the debilitating effects of hypothyroidism and its use successfully promotes iodine uptake and increases the sensitivity of serum Tg testing. The risk of causing serious side-effects recommends performing skull magnetic resonance and radionuclide bone scan in cases of suspected brain or skeletal metastases.     

Serum thyroglobulin levels at the time of 131I remnant ablation just after thyroidectomy are useful for early prediction of clinical recurrence in low-risk patients with differentiated thyroid carcinoma

We investigated whether serum thyroglobulin (Tg) measured at the time of remnant ablation (ablation-Tg) could be a prognostic indicator complementary to serum Tg levels at the time of the first diagnostic whole-body scan (WBS) after thyroid hormone withdrawal (control-Tg; approximately 6-12 months after ablation-Tg) and whether ablation-Tg could predict the persistence or recurrence of disease in low-risk patients with differentiated thyroid carcinoma. Patients with differentiated thyroid carcinoma (n = 268) treated with total or near-total thyroidectomy followed by immediate (131)I remnant ablation were studied. Patients with anti-Tg autoantibodies and those showing evidence of extracervical metastases were excluded. Two patients showing remnant uptake on follow-up diagnostic WBS received a second ablation. We found significant correlation between ablation-Tg and control-Tg levels; 114 of 143 patients (80%) with ablation-Tg greater than 2 microg/liter showed detectable (>/=1 microg/liter) control-Tg, and 70 of 125 (56%) patients with ablation-Tg 2 microg/liter or less showed undetectable (<1 microg/liter) control-Tg [odds ratio 5.1, 95% confidence interval (CI) 3.0-8.9, P < 0.001]. When the 268 patients were followed up for a mean period of 5.7 +/- 1.4 yr (range 2.8-8.3 yr), 35 (13%) had recurrences; 73 (27%) were classified as "Tg positive, no evidence of disease"; and 160 (60%) showed complete remission. Of 143 patients with ablation-Tg greater than 2 microg/liter, recurrence was observed in 33 cases (23%); "Tg positive, no evidence of disease," was observed in 52 cases (36%); and complete remission was observed in 58 cases (41%). Of 125 patients with ablation-Tg 2 microg/liter or less, two patients (2%) showed recurrence during the follow-up; 21 patients (17%) were regarded as "Tg positive, no evidence of disease"; and 102 patients (81%) showed complete remission. The positive predictive value for recurrence in patients having ablation-Tg greater than 2 microg/liter was found to be 23.1% (33 of 143 patients, 95% CI 16.4-30.8%). The negative predictive value for recurrence in patients having ablation-Tg 2 microg/liter or less was found to be 98.4% (123 of 125 patients, 95% CI 94.4-99.8%). These data indicate that serum Tg levels measured at the time of immediate postoperative (131)I remnant ablation correlated well with serum Tg levels at the time of the initial diagnostic WBS and had a complementary role for predicting persistence or recurrence of disease in the earliest postoperative period.     

Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma.

Stimulation with recombinant human TSH (rhTSH) has been introduced in clinical practice as an effective alternative to thyroid hormone withdrawal for the diagnostic follow-up (Tg measurement and 131-iodine whole-body scan) of patients with differentiated thyroid cancer. The present study was specifically aimed to evaluate the utility of rhTSH-stimulated serum Tg measurements in patients with undetectable serum Tg values, on L-T(4) therapy, as the only test to differentiate patients with persistent disease from patients who are disease-free. We studied 72 consecutive patients with differentiated thyroid cancer, previously treated with near-total thyroidectomy and 131-I thyroid ablation. Admission criteria were: an undetectable (<1 ng/ml) serum Tg, on L-T(4) therapy, and negative anti-Tg antibodies. The study design consisted of a Tg-stimulation test after rhTSH, during L-T(4), followed by diagnostic WBS and serum Tg measurement off L-T(4). After rhTSH, serum Tg remained undetectable in 41 of 72 patients (56.9%). A negative rhTSH Tg test agreed with an undetectable hypo-Tg in 36 of 41 cases (87.8%), all without evidence of metastatic disease at hypo-WBS. In 5 of 41 cases (12.2%), hypo-Tg was detectable (1.1-7.8 ng/ml), in association with negative hypo-WBS or faint uptake in the thyroid bed. Serum Tg converted from undetectable to detectable after rhTSH in 31 of 72 patients (43.1%), with a peak Tg ranging between 1.2 and 23.0 ng/ml. Hypo-Tg was always detectable in these patients (100% concordance), and it was significantly higher than rhTSH-stimulated Tg (P < 0.0002). Hypo-WBS was positive in 23 of 31 patients (74.2%), showing thyroid residues in 12, cervical lymph nodes in 7, and lung metastases in 4 cases. In 8 of 31 cases, hypo-WBS was negative, despite detectable serum Tg. Thus, rhTSH-stimulated Tg was able to detect all cases of documented local or distant metastases. In conclusion, our data indicate that, in patients with undetectable basal levels of serum Tg, rhTSH-stimulated Tg represents an informative test to distinguish disease-free patients (not requiring WBS) from diseased patients (requiring further diagnostic and/or therapeutic procedures).     

Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma

Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.     

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study

CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.     

Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid.

We performed a retrospective record review of patients who received large lobar remnant ablation after surgery for well-differentiated thyroid carcinoma including 30 with papillary carcinoma, 14 with follicular carcinoma, and 6 with Hürthle cell carcinoma. We compared these 50 patients to a group of patients who underwent total or near-total thyroidectomy for well-differentiated thyroid carcinoma. The ablation group was treated with single outpatient doses of 29.9 mCi (131)I to prepare for whole-body radioiodine scanning. Subsequent serum thyrotropin (TSH) concentration during thyroid hormone withdrawal was greater than 25 microU/mL in 94% of patients. The mean TSH in this population (76 microU/mL) was not statistically different from a group of 50 patients who underwent total or near-total thyroidectomy (mean, TSH 71 microU/ml p = 0.84). Twenty-four hour radioiodine uptake post-29.9 mCi (131)I ablation was less than 1% in 80% of patients. The mean radioiodine uptake (0.8%) in the lobe ablation population was significantly lower than in patients treated with total thyroidectomy (mean, 2.4%, p < 0.001). There was minimal morbidity after 29.9 mCi (131)I ablation of large lobar remnants. Outpatient 29.9 mCi (131)I ablation is a safe, effective, and less costly alternative to completion thyroidectomy in selected patients. Although we included patients with both papillary and follicular carcinoma in our review, we recommend this method for patients with minimally invasive follicular carcinoma requiring whole body scanning, even with large postsurgical remnants in place.     

Pretreatment with a single,low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.     

Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal

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 (131)I 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 (131)I 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 micro U/ml (range, <0.005-11.9 micro U/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.     

Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer.

Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasible, and malignant tissue ablation by 131I administration. This procedure requires levothyroxine withdrawal to obtain high levels of endogenous thyrotropin (TSH) to stimulate radioactive iodine uptake by the malignant tissue. Levothyroxine withdrawal may cause severe adverse effects and complications in patients with concomitant illness or advanced metastatic disease. The recent availability of recombinant human thyrotropin (rhTSH) allows diagnostic whole-body scan (WBS) and thyroglobulin testing without levothyroxine withdrawal. We describe six patients with metastatic differentiated thyroid cancer (DTC) and concomitant illness in whom the use of rhTSH was effective in preventing the complications that patients had previously experienced during hypothyroidism consequent to levothyroxine withdrawal. Our results indicate that rhTSH can be particularly advantageous to avoid signs and symptoms of hypothyroidism and complications because of associated diseases in view of 131I treatment of DTC metastases in selected cases in which levothyroxine withdrawal may be dangerous. Its efficacy to treat advanced metastatic disease should be further investigated.     

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.     

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   

Use of thyroid ultrasound volume in calculating radioactive iodine dose in hyperthyroidism.

One hundred twenty-one patients treated with 131I had a thyroid ultrasound to measure thyroid volume precisely. This volume measurement was used to determine the radioactive iodine dose. The average size (+/-SEM) of the thyroid glands measured in this manner was 39.7 cm3 +/- 1.9 cc. A significant correlation was found in the estimated size of the gland by the endocrinologists and the ultrasound volume. Of the 121 patients, 89 patients had the same 131I microcurie per gram of tissue factor to determine the radioactive iodine dose. This group of patients was further evaluated in this study. The average 131I dose (+/-SEM) given was 13.2 mCi +/- 0.5 mCi. The average time until hypothyroidism was achieved 2.85 +/- 0.14 months. Ultrasound provides a safe and precise way to determine actual thyroid size when calculating 131I doses.     

Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin

BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.     

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.     

Effects of 0.9 mg recombinant human thyrotropin on thyroid size and function in normal subjects: a randomized, double-blind, cross-over trial

The effect of recombinant human TSH (rhTSH) on thyroid function and ultrasonically determined thyroid volume was investigated in nine healthy euthyroid male volunteers. Each received either 0.9 mg rhTSH or isotonic saline in a randomized order, and thyroid volume and function were closely monitored during the following 28 d. No significant changes were observed after saline injection. After rhTSH stimulation, the median serum TSH increased from 2.03 mU/liter (range, 0.99-3.07 mU/liter) to more than 200 mU/liter (range, 78.9 to >200.0 mU/liter) after 4 h, with a subsequent rapid decline. Mean (+/-SEM) serum free T(4) and free T(3) peaked at 48 h with levels 204.7 +/- 26.1% and 226.9 +/- 31.4%, respectively, above baseline (P < 0.001). Twenty-four hours after rhTSH stimulation, mean (+/-SEM) thyroid volume was significantly increased by 23.3 +/- 5.8% (P = 0.003) and after 48 h by 35.5 +/- 18.4% (P = 0.02). On d 4 the mean thyroid enlargement had reverted to baseline values. One individual developed a 90-ml tender thyroid enlargement (initially 21 ml) 36 h after rhTSH administration, associated with a very high level of serum thyroglobulin. It is concluded that 0.9 mg rhTSH may result in a profound stimulation of not only thyroid function but also of thyroid size, appearing in the period 1-4 d after injection. Further dose-response studies are needed to clarify the potential hazards before routine use, for example in the context of (131)I therapy and goiter.     

Reevaluation of the impact of a stringent low-iodine diet on ablation rates in radioiodine treatment of thyroid carcinoma.

Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on ablation in patients with differentiated thyroid cancer postthyroidectomy are dated. We retrospectively reviewed first-time, short-term ablation rates for 44 LID patients and 50 patients following a regular diet (RD) who were verbally instructed to avoid salt, seafood, and multivitamins containing iodine. Patients who had undergone ablation were given between 100 and 200 mCi of 131I, depending on the presence of metastases. We found a 68.2% ablation rate for LID patients, compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53). We observed a dose-response relationship for both patient groups, with higher ablation rates corresponding to higher doses of radioiodine administered. We also measured iodine levels in spot urine samples from 7 matched LID patients and 7 matched RD adherents (healthy volunteers) prediet and postdiet as well as 39 healthy volunteers. LID patients had a lower mean urinary iodine level postdiet (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4). Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the RD reduced urinary iodine by 23.6%. Although differences in the reduction of urinary iodine levels between the LID and the RD were substantial, both groups experienced equivalent outcomes. The level of iodine in the American diet has progressively decreased, and may be much lower now than when prior LID studies were conducted. We suggest that prescribing a refined, less stringent diet that avoids high-iodine-containing foods would offer equivalent outcomes with increased patient convenience.