Radioiodine Ablation Of Thyroid Remnants Research Articles

Radioiodine Ablation of Thyroid Remnants in Patients with Graves' Orbitopathy.

Our purpose was to assess response after ablation of thyroid remnants (ATR) with radioactive iodine therapy in patients with unstable Graves' orbitopathy (GO) after subtotal thyroidectomy. Methods: Thirty patients with mild (n = 4, 13%), moderate-to-severe (n = 25, 83%), or very severe GO (n = 1, 3%) were analyzed in this retrospective study. The primary endpoint was the improvement of GO-related symptoms as assessed by clinical activity scores, NOSPECS, and soft-tissue inflammation scores at 3 and 12 mo after ATR. Ablation success was defined by a decrease in 99mTc uptake on thyroid scintigraphy, remnant volume, and thyrotropin receptor antibody levels at 3 mo after ATR. Results: Twelve months after ATR, clinical activity scores, NOSPECS, and soft-tissue inflammation scores showed a significant decrease from 3.4 to 1.3 (P < 0.0001), 5.9 to 4.9 (P = 0.007), and 4.7 to 2.1 (P = 0.0001), respectively. The GO was inactive in 27 of the 30 (90%) patients after 3 mo and in 29 (97%) after 12 mo. No new activation of GO occurred. Remnant volume (1.4 vs. 0.4 cm3, P = <0.0001), mean thyrotropin receptor antibody level titer (19.02 vs. 13.37 IU/L, P < 0.0001), and 99mTc uptake (0.5% vs. 0.1%; n = 12; P = 0.04) decreased significantly until 3 mo after ATR. Discussion: Radioactive iodine therapy after thyroidectomy can successfully ablate residual thyroid remnants, leading to an improvement in GO, a reduction in inflammatory activity, and stabilization of thyroid function. Thus, scintigraphy should be considered for patients with unstable GO after thyroidectomy to rule out thyroid remnants.

Post-operative radioiodine therapy (RaIT) as adjuvant therapy in low–intermediate risk differentiated thyroid cancer

For many years, thyroid surgery and radioiodine therapy for thyroid remnant ablation (i.e. post-operative RaIT) have been the first-line therapeutic approaches in differentiated thyroid carcinoma (DTC). In the latest American Thyroid Association Guidelines (ATA), post-operative RaIT is not indicated in low-risk DTC, while no clear indication is postulated regarding low- to intermediate-risk patients, even if it is discouraged in most of them. The European Association of Nuclear Medicine did not endorse ATA guidelines since the role of nuclear medicine was marginalized in patients affected by low- or low- to intermediate-risk cancers. The present review evaluates the adjuvant role of post-operative RaIT in low and low- to intermediate-risk DTC patients. The terms radioiodine adjuvant therapy, radioiodine adjuvant treatment, thyroid remnant ablation, radioiodine thyroid remnant ablation, radioiodine therapy and radioiodine treatment were used to search MEDLINE for papers published from January 2008 to May 2018. Among 895 papers, we considered 8 in which patients underwent post-operative RaIT and the results of post-therapy whole body scans (pT-WBS) were reported. pT-WBS identified metastases in 282 out of 1622 patients (17.4%). All except 28 metastatic patients were affected by either low- or low- to intermediate-risk DTC. Metastases were confirmed by (targeted)-morphological and/or morphofunctional and/or morphometabolic studies in about 40% of patients. According to the presented data, slightly less than 20% of low- or low- to intermediate-risk DTC patients showed metastases at pT-WBS. Thus, in our opinion post-operative RaIT should be considered as an adjuvant therapy also in low and low- to intermediate-risk DTC patients.

Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography.

Radioiodine therapy (RAI) has proven effective for the treatment of patients exhibiting differentiated thyroid cancer (DTC) with pulmonary metastases. However, the early detection of metastasis remains challenging, and various studies have reported variations in radioiodine treatment efficacy. The present study investigated whether RAI is an effective method for the treatment of DTC with pulmonary metastases undetected by computed tomography (CT). A retrospective study was performed, analyzing iodine-131 (131I) therapy in 21 DTC patients with lung metastases that were undetected by CT. All 21 patients were initially treated with radioiodine ablation of thyroid remnants. Routine chest CT was performed prior to 131I treatment without diagnostic radioiodine whole-body scanning (DxWBS), and post-therapeutic WBS was performed 3–5 days subsequent to oral administration of 131I. The overall effectiveness rate was 95.2% (20/21). The rates for complete response (CR), partial response and no response were 23.8 (5/21), 71.4 (15/21) and 4.8% (1/21), respectively. There were 12 patients with diffuse uptake, and the remaining 9 patients demonstrated focused and low uptake. The difference in CR rate between diffuse uptake and focused uptake patients was not statistically significant (P=0.123). A correlation was observed between thyroglobulin (Tg) levels and extrapulmonary metastases. All patients exhibited extrapulmonary metastases when Tg levels were >87.5 ng/ml (area under receiver operating characteristic curve, 1.0; P<0.001). Overall, DTC patients with lung metastases undetected by CT imaging responded well to 131I radiotherapy and demonstrated a positive prognosis. Serum Tg levels prior to 131I treatment may correlate with metastasis, and this may suggest a requirement for the performance of DxWBS prior to radiotherapy.

A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq 131I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital.Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of 131I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq 131I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of 131I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05.Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319).By a diagnostic scan of 74 MBq 131I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer

The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

Patients With Differentiated Thyroid Cancer Who Underwent Radioiodine Thyroid Remnant Ablation With Low-Activity 131I After Either Recombinant Human TSH or Thyroid Hormone Therapy Withdrawal Showed the Same Outcome After a 10-Year Follow-up

No long-term follow-up data are available for differentiated thyroid carcinoma (DTC) patients prepared with either exogenous or endogenous TSH and treated with low-activity (1.1 GBq [30 mCi]) radioiodine (¹³¹I). The aim of this study was to evaluate the 10-year follow-up of DTC patients who underwent remnant ablation with 1.1 GBq ¹³¹I after l-T4 withdrawal, recombinant human TSH (rhTSH) administration, or both. A total of 159 DTC patients treated with total thyroidectomy and 1.1 GBq (30 mCi) of ¹³¹I for remnant ablation and stimulated with rhTSH and/or endogenous TSH were separated into ablated (n = 115) and not ablated (n = 44) patients and prospectively followed-up for at least 10 years. In addition, we evaluated several features that could correlate with the final status of patients. During the follow-up, 4 of 115 (3.5%) ablated patients showed a recurrence and 1 was successfully cured. Among not ablated patients, 16 of 44 (36.4%) had a persistent disease. At the end of the 10-year follow-up, 140 of 159 (88.1%) patients were disease-free, whereas 19 of 159 (11.9%) remained affected. No correlation was found with the type of TSH stimulation, and no other clinical and pathological features showed any correlation with the final status. However, low levels of stimulated serum thyroglobulin (<5.4 ng/mL) at first control after remnant ablation identified a subgroup of not ablated patients who became spontaneously cured. Long-term outcomes are similar in DTC patients treated with 1.1 GBq (30 mCi) ¹³¹I and prepared either with rhTSH or endogenous TSH. It is of interest that serum thyroglobulin at first control after ablation can have a prognostic role.

Low- or High-Dose Radioiodine Remnant Ablation for Differentiated Thyroid Carcinoma: A Meta-Analysis

There is uncertainty over the dose of (131)I required for thyroid remnant ablation. Most previous studies have been inadequately powered to establish the best fixed dose of (131)I for effective ablation. The aim of the study was to assess the effects of low- vs high-dose regimens of radioiodine in thyroid remnant ablation for patients with differentiated thyroid carcinoma. Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS (all until September 2012). Randomized controlled trials that assess the efficacy of low- or high-dose of radioiodine ablation of thyroid remnants were collected. Two authors performed the data extraction independently. Nine randomized controlled trials involving 2569 patients were included. The 1100-MBq vs the 3700-MBq radioiodine showed no statistically significant difference in successful thyroid remnant ablation (risk ratio [RR], 0.91 [0.79 to 1.04]; P = .15), both the 1100 vs the 1850 MBq (RR, 0.95 [0.83 to 1.10]; P = .52) and the 1850 vs the 3700 MBq (RR, 1.00 [0.85 to 1.17]; P = .98) also showed no significant differences (95% confidence intervals were calculated for each estimate). Also, no significant differences existed in quality-of-life scores on the SF-36 between different (131)I-dose groups both on the day of ablation (RR, 0.15 [-0.65 to 0.96], P = .71; I(2) = 29%, P = .24) and 3 months after ablation (RR, -1.1 [-2.37 to 0.17], P = .09; I(2) = 22%, P = .26). A low dose of 1100 MBq radioiodine showed significant benefits in reducing adverse effects (total RR, 0.65 [0.55 to 0.77], P < .1; I(2) = 31%, P =.14) and shorter hospital isolation (RR, 0.4 [0.32 to 0.50]; P < .05). The low dose of 1100 MBq radioiodine activity is sufficient for thyroid remnant ablation as compared to 3700 MBq radioiodine activity with similar quality of life, less common adverse effects, and a shorter hospital stay.

Carbohydrate-Mediated Polyethylene Glycol Conjugation of TSH Improves Its Pharmacological Properties

Thyrogen (thyrotropin alfa for injection), recombinant human TSH (rhTSH), has been successfully used to enhance diagnostic radioiodine scanning and thyroglobulin testing in the follow-up of patients with thyroid cancer and as an adjunctive treatment for radioiodine thyroid remnant ablation. However, the short half-life of rhTSH in the circulation requires a multidose regimen. We developed novel sialic acid-mediated and galactose-mediated conjugation chemistries for targeting polyethylene glycol (PEG) to the three N-linked glycosylation sites on the protein, to prolong plasma half-life by eliminating kidney filtration and potential carbohydrate-mediated clearance. Conjugates of different PEG sizes and copy numbers were screened for reaction yield, TSH receptor binding, and murine phamacokinetics/pharmacodynamics studies. The best performing of these products, a 40-kDa mono-PEGylated sialic acid-mediated conjugate, exhibited a 3.5-fold longer duration of action than rhTSH in rats, as a 5-fold lower affinity was more than compensated by a 23-fold extension of circulation half-life. Biochemical characterization confirmed conjugation through the sialic acids. Correlation of PEG distribution on the three N-linked glycosylation sites and the PEG effect on receptor binding supported the previously reported structure-function relationship of rhTSH glycosylation. This long-acting rhTSH has the potential to significantly improve patient convenience and provider flexibility while reducing potential side effects associated with a sudden elevation of serum TSH.

Radioiodine Thyroid Remnant Ablation after Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal in Patients with High-Risk Differentiated Thyroid Cancer

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. “No evidence of disease” (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. “Persistent disease” was failure to achieve NED, “recurrence,” loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Treatment room length-of-stay and patient throughput with radioiodine thyroid remnant ablation in differentiated thyroid cancer

We sought to empirically compare treatment room length-of-stay and patient throughput for recombinant human thyroid-stimulating hormone (rhTSH)-aided thyroid remnant ablation with thyroid hormone withdrawal (THW)-aided ablation in patients with differentiated thyroid carcinoma (DTC). We retrospectively reviewed charts of all eligible (near) totally thyroidectomized patients with DTC undergoing ablation and 1-year ablation success evaluation at our tertiary referral centre from January 2003 to February 2009 (N=274). M1 disease caused exclusion unless discovered by a postablation scan or present when rhTSH was the only tolerable stimulation method. We extracted data on the length-of-stay, defined as the time between treatment room admission and discharge, and patient throughput, defined as patients ablated per treatment room per week. The treatment room discharge criterion was a whole-body dose rate of less than 60 μSv/h at 50 cm. The treatment groups (rhTSH, n=187; THW, n=87) had mostly statistically similar characteristics, but differed in primary tumour status distribution. In addition, at ablation, the rhTSH patients had a greater prevalence of prior diagnostic scintigraphy, higher mean serum TSH, and shorter interval since surgery, and received a 5.6% larger mean ablation activity. On average, rhTSH patients had a significantly lower peak whole-body dose rate (57.1 vs. 83.4 μSv/h at 50 cm; P<0.0001) and a significantly shorter treatment room stay than did the THW patients (1.41 vs. 2.02 days; P<0.001). rhTSH use allowed significantly more patients to be ablated per room per week (2.7 vs. 1.2; P<0.001). Relative to THW, rhTSH use to aid ablation reduced mean treatment room length-of-stay by almost one-third and more than doubled the average weekly patient throughput, both of which were significant differences.

The Role of Routine Diagnostic Radioiodine Whole-Body Scintigraphy in Patients with High-Risk Differentiated Thyroid Cancer

Follow-up diagnostic radioiodine whole-body scintigraphy (DxWBS) is still advised for high-risk patients with differentiated thyroid cancer. The aim of this study was to evaluate the additional value of DxWBS to stimulated thyroglobulin measurement in high-risk patients. The results of DxWBS and thyroglobulin measurements performed 6-12 mo after surgery and radioiodine thyroid remnant ablation in patients with differentiated thyroid cancer were retrospectively evaluated for 112 patients with high-risk features for recurrence (R3/T4 and N1). One patient had an undetectable thyroglobulin level, with DxWBS results suggestive of cervical recurrence. DxWBS was found to be false-positive. Of the patients with detectable thyroglobulin levels, the DxWBS results were negative in 65 and positive in only 8. The 6 patients positive for thyroglobulin antibody had negative DxWBS results. The remaining patients had an undetectable thyroglobulin level and negative DxWBS results. Because undetectable stimulated thyroglobulin levels have a negative predictive value of 100%, DxWBS offers no information additional to recombinant human thyroid-stimulating hormone-stimulated thyroglobulin measurements in patients with high-risk differentiated thyroid cancer.

Radioiodine thyroid remnant ablation in patients with differentiated thyroid carcinoma (DTC): prospective comparison of long-term outcomes of treatment with 30, 60 and 100 mCi

BackgroundThe aim of this study is to compare the effectiveness of 131I therapy between three groups of DTC patients who received 30, 60 or 100 mCi for thyroid remnant ablation after total thyroidectomy and were postoperatively judged with low risk of cancer recurrence.MethodsThe project was designed as a two-stage, prospective randomized clinical trial. In 1998-2001 in a randomized prospective study the early comparison of treatment with 30 mCi vs 60 mCi suggested the lower 131I activity to be less effective, whereas in 2003-2005 the comparison between 60 vs 100 mCi showed no significant differences. The present study comprises the long-term assessment of the disease course in 3 study groups.ResultsA group of 309 DTC patients (285 women and 24 men) with no clinical, histopathological, sonographical or biochemical signs of persistent disease were included after total thyroidectomy and appropriate extent of neck lymph node dissection (265 with papillary and 44 with follicular thyroid cancer). For radioiodine thyroid remnant ablation, 30 mCi of 131I was applied in 86 patients, whereas 60 mCi in 128 and 100 mCi in 95 patients. The median follow-up was 10 years (2-12) for subjects treated with 30 mCi and 60 mCi and 6 years (2-6) for patients treated with 100 mCi of 131I. In the first evaluation, published previously, we observed that because of incomplete thyroid remnant ablation, the second 131I treatment was necessary in 10% patients, without difference between groups treated with 60 and 100 mCi and in 22% patients treated with 30 mCi. All patients entered full remission. To evaluate the long-term outcome of the adjuvant 131I treatment, the course of the follow-up and the most recent disease status were assessed by sonography, radiological examinations and serum Tg estimation (on LT4-suppressive treatment). Within the whole observation period local relapse was stated in 2 (2.4%), 4 (3%) and 3 (3%) patients treated with 131I activities of 30 mCi, 60 mCi and 100 mCi respectively and serum Tg concentration on LT4-suppressive treatment was low, without differences between groups.ConclusionsNo significant differences in the 5 years efficacy of thyroid remnant radioiodine ablation using 30, 60 and 100 mCi were observed in low-risk DTC patients operated by total thyroidectomy and neck lymph node dissection. However, patients treated initially with 30 mCi, required second course of radioiodine in 22%, while this was necessary only in 13,3% and 11,2% of patients treated with 60 mCi and 100 mCi respectively.

Radioiodine Ablation for Differentiated Thyroid Cancer—None, One Dose or Two?

Patients with good prognosis differentiated thyroid cancer are at risk from over-treatment with radioiodine thyroid remnant ablation. Some with unfavourable localised disease might benefit from an elective second dose.

Recurrence After Treatment of Micropapillary Thyroid Cancer

Despite very low mortality associated with micropapillary thyroid cancer, locoregional recurrence is common and controversy exists regarding optimal surgical treatment and the role of adjunctive radioiodine. The National Thyroid Cancer Treatment Cooperative Study Group Registry was analyzed for recurrences in patients with unifocal versus multifocal micropapillary cancer, with or without nodal disease, depending upon the extent of surgery and the use of adjunctive radioiodine. Six hundred eleven patients considered disease-free after initial therapy were followed for 2572 person-years. Thirty patients (6.2%) had recurrences detected at a mean 2.8 years after primary treatment. Recurrences did not differ between patients with unifocal and multifocal disease overall; however, among patients who received less than a near-total thyroidectomy (NTT), those with multifocal disease had more recurrences than those with unifocal disease (18% vs. 4%, p = 0.01). Patients with multifocal disease who had a total (T) or NTT trended toward fewer recurrences than those undergoing less than an NTT (6% vs. 18%, p = 0.058). In patients who did not receive radioiodine therapy, recurrence was more common in patients with multifocal disease versus unifocal disease (7% vs. 2%, p = 0.02). However, radioiodine did not reduce recurrences in patients with multifocal disease or patients with positive nodes. Patients with positive nodes had more recurrences than node-negative patients regardless of surgical extent or use of radioiodine. Patients with micropapillary multifocal disease have a reduced risk of recurrence after a T/NTT compared with less surgery. A randomized, controlled trial is necessary and feasible to determine if radioiodine ablation of thyroid remnants is advantageous in patients with intrathyroidal micropapillary cancer.

Chromosome Translocation Frequency after Radioiodine Thyroid Remnant Ablation: A Comparison between Recombinant Human Thyrotropin Stimulation and Prolonged Levothyroxine Withdrawal

Thyroid remnant ablation of differentiated thyroid carcinoma (DTC) patients is traditionally performed after levothyroxine withdrawal. Recombinant human TSH (rhTSH) administration increases serum TSH levels without inducing hypothyroidism. The aim of the study was to investigate the frequency of chromosome translocations in DTC patients after the first (131)I therapeutic dose and compare the frequency of translocations between DTC patients off levothyroxine and those receiving rhTSH. A total of 20 DTC patients were randomly assigned to levothyroxine withdrawal [(30 d) group A; n=10, nine women; mean age 48.5+/- 19.2 yr] or rhTSH injections [(0.9 mg im per 2 consecutive days) group B; n=10, eight women; mean age 50.4+/- 18.8 yr] before undergoing (131)I activity (3.7 GBq). The frequency of translocations in peripheral lymphocytes was analyzed by tricolor fluorescence in situ hybridization with whole-chromosome-specific probes for chromosomes 1, 4, and 8. Lymphocytes were stained routinely (about 500 each time). The two groups showed similar baseline translocation frequency. After (131)I administration, the total chromosomal translocation rate was significantly lower in group B than group A (P = 0.02). The frequency of translocations increased significantly in group A only (P = 0.01 vs. baseline). Rearrangement specifically involved chromosomes 4 and 8 (P = 0.02 vs. baseline). Our preliminary data show that in hypothyroid status (131)I ablation therapy induces a higher translocation rate, especially in chromosomes 4 and 8. This finding, in agreement with previous dosimetric reports, suggests that whereas inducing a low extrathyroid exposure, rhTSH reduces the potential risk of chromosomal aberration associated with blood irradiation.

What role for recombinant human TSH in the treatment of metastatic thyroid cancer?

The introduction into clinical practice of recombinant human thyroid-stimulating hormone (rhTSH) has marked a turning point in the management of patients with differentiated thyroid cancer. RhTSH offers a safe and reliable alternative to thyroid hormone withdrawal by avoiding both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the potential risk of cancer growth due to a long-lasting endogenous TSH stimulation. In the follow-up of thyroid cancer patients, rhTSH stimulated thyroglobulin is now routinely proposed as it has been shown to be as sensitive as endogenously stimulated thyroglobulin for the detection of residual and metastatic cancer [1]. More recently, the use of rhTSH has been approved for the preparation of adult low-risk patients for postsurgical radioiodine ablation of thyroid remnants with 3.7 GBq I [2]. Although the activity necessary to achieve a comparable rate of ablation is probably higher than that required under hypothyroidism [3, 4], the use of rhTSH is associated with a lower whole-body radiation exposure [5] and allows a shorter hospitalization length, which partially compensates for its cost [6]. The use of rhTSH in the treatment of metastatic thyroid cancer is much more controversial. Although rhTSH has not been formally approved so far for this indication, it has been used off-label since the 1990s to treat patients in which thyroid hormones could not be stopped [7]. This includes patients unable to raise an adequate endogenous TSH response, either because of hypopituitarism or continued production of thyroxine by a thyroid remnant or metastatic tumour, and patients in poor condition due to advanced disease. The results obtained in some patients are encouraging. One may raise the question whether a wider use of rhTSH can be advovated in the therapeutic setting. In our opinion, both clinical and biological data from the literature argue against a more liberal use of rhTSH for the therapy of metastatic thyroid cancer. First, tumour cells of thyroid cancer have a reduced expression of most thyroid-specific genes, including the TSH receptor and the Na/I symporter (NIS) gene [8]. Although the standard two injections protocol of rhTSH provides a high plasma TSH peak, roughly in the range 100–150 mIU/L 24 h after the second injection [9], the concentration increase is short-lived [10]. In order to improve the number of NIS and TSH receptors, and thus enhance the iodine-trapping ability of the cells, a high and prolonged period of TSH stimulation elevation is desirable [11]. Indeed, a I whole-body scan under hypothyroidism is more sensitive than the same scan after rhTSH administration [12]. It should be remembered that a posttherapeutic scan of good quality is an invaluable tool to discover unsuspected metastases and to assess the efficacy of repeated I treatment in metastatic patients [13]. Second, published experience shows that rhTSH stimulates the uptake of radioiodine in metastatic lesions [7]. However, prospective randomized studies comparing the relative efficacy of rhTSH-aided metastatic cancer treatEur J Nucl Med Mol Imaging (2009) 36:883–885 DOI 10.1007/s00259-008-1046-0

Diagnostic and therapeutic use of recombinant human TSH (rhTSH) in differentiated thyroid cancer

Traditionally, withdrawal of thyroid hormone to increase serum levels of thyroid-stimulating hormone (TSH) has been used in patients with differentiated thyroid carcinoma (DTC) to optimize radio-iodine uptake and serum thyroglobulin (Tg) stimulation during follow-up and in preparation for radio-iodine therapy. However, this procedure is associated with signs and symptoms of hypothyroidism which negatively affect the patient's quality of life. Recombinant human thyrotropin (rhTSH) has provided an effective alternative to thyroid hormone withdrawal. After favourable experimental trials in humans, rhTSH obtained regulatory approval in North America and in Europe as a diagnostic tool, and more recently as a preparation for radio-iodine thyroid remnant ablation. Since then, rhTSH has radically changed the diagnostic and therapeutic management of DTC patients. This review will focus on the clinical application of rhTSH in the management of DTC, highlighting current indications and future perspectives.

Review on the Occasion of a Decade of Recombinant Human TSH: Prospects and Novel Uses

The introduction of recombinant human thyroid-stimulating hormone (rhTSH) almost a decade ago represents a remarkable achievement in the history of clinical thyroidology. rhTSH now contributes substantially to the diagnostic approach to thyroid cancer, offering a reliable and safe alternative to thyroid hormone withdrawal by avoiding the morbidity of hypothyroidism. Several recent studies have also demonstrated the efficacy of radioiodine ablation of thyroid remnants after preparation with rhTSH. Moreover, the use of rhTSH in this context is associated with a lower whole body exposure to radiation compared to thyroid hormone withdrawal. Although not approved officially, rhTSH-assisted treatment of locoregional or distant metastatic disease may be the treatment of choice for patients in whom hypothyroidism may be relatively contraindicated, such as the very young and the aged, although additional efficacy studies are necessary. The compound has also been shown to be useful in the treatment of nontoxic multinodular goiter, especially when the radioiodine uptake is low. Finally, rhTSH may prove to be useful in studying the functional reserve of thyroid in the aging process, as well as the putative role of the TSH receptor in extrathyroidal tissue, such as lymphocytes, osteocytes, and adipocytes.

Radioiodine Ablation of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma: Results of an International, Randomized, Controlled Study

Radioiodine Ablation of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma: Results of an International, Randomized, Controlled Study

Radioiodine Ablation of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma: Results of an International, Randomized, Controlled Study

Radioiodine Ablation of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin in Differentiated Thyroid Carcinoma: Results of an International, Randomized, Controlled Study