Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Absorbed dose coefficients for adult thyroid cancer patients undergoing radioiodine therapy.

Use of radioactive iodine (RAI) for thyroid cancer patients is accompanied by elevated risks of radiation-induced adverse effects due to significant radiation exposure of normal tissues or organs other than the thyroid. The health risk estimation for thyroid cancer patients should thus be preceded by estimating normal tissue doses. Although organ dose estimation for a large cohort often relies on absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq-1) based on population models, no data are available for thyroid cancer patients. In the current study, we calculated absorbed dose coefficients specific for adult thyroid cancer patients undergoing RAI treatment after recombinant human TSH (rhTSH) administration or thyroid hormone withdrawal (THW). We first adjusted the transfer rates in the biokinetic model previously developed for THW patients for use in rhTSH patients. We then implemented the biokinetic models for thyroid cancer patients coupled withSvalues from the International Commission on Radiological Protection (ICRP) reference voxel phantoms to calculate absorbed dose coefficients. The biokinetic model for rhTSH patients predicted the extrathyroidal iodine decreasing noticeably faster than in the model for THW patients (calculated half-times of 12 and 15 h for rhTSH administration and THW, respectively). All dose coefficients for rhTSH patients were lower than those for THW patients with the ratio (rhTSH administration/THW) ranging from 0.60 to 0.95 (mean = 0.67). The ratio of the absorbed dose coefficients in the current study to the ICRP dose coefficients, which were derived from models for normal subjects, varied widely from 0.21 to 7.19, stressing the importance of using the dose coefficients for thyroid cancer patients. The results of this study will provide medical physicists and dosimetrists with scientific evidence to protect patients from excess exposure or to assess radiation-induced health risks caused by RAI treatment.

Effect of preparation method for radioactive iodine therapy on serum electrolytes.

PURPOSE: Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT. MATERIALS AND METHODS: From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L). RESULTS: Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019). CONCLUSION: THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.

Recombinant human thyrotropin versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer: Experience in a South Taiwanese medical center.

This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I131 dose were the prognostic factors affecting the excellent response rate. In conclusion, the THW and rhTSH preparations for RIA were similar in terms of the excellent response rates and subgroup clinical outcomes.

Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with 131I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.

It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.

Comparison of thyroid hormone withdrawal and recombinant human thyroid-stimulating hormone administration for adjuvant therapy in patients with intermediate- to high-risk differentiated thyroid cancer.

OBJECTIVE: To compare the clinical outcome in patients who received adjuvant therapy with radioactive iodine (RAI) using different preparation methods, namely, thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH), after undergoing thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association criteria. METHODS: Between May 2012 and October 2018, 136 patients who underwent adjuvant therapy with high-dose (3700 MBq) RAI for DTC without any metastatic lesions or macroscopic residual lesions after surgical resection were retrospectively selected. Patients were excluded if distant metastasis was confirmed during adjuvant therapy or if the outcome could not be confirmed; thus, 112 patients were finally evaluated. Patients underwent either a 3-week I restriction with thyroxine withdrawal or a 2-week I restriction with rhTSH administration. The serum thyroglobulin (Tg) concentration was measured, and 131I scintigraphy (370 MBq) was performed 6-12 months after adjuvant therapy. The definition of the initial achievement of adjuvant therapy was the disappearance of the uptake of 131I at the thyroid bed and serum Tg concentration < 2.0 ng/mL. The results of the adjuvant therapy between the groups were compared using the Fisher's exact test, and the TSH levels and estimated glomerular filtration rate (eGFR) were compared using the Welch's t test. RESULTS: The THW and rhTSH groups included 47 and 65 patients, respectively, and the intermediate- and high-risk groups included 63 and 49 patients, respectively. No patient was assigned to the low-risk group. In the THW and rhTSH groups, the initial RAI adjuvant therapy goal was achieved in 30/47 (63.8%) and 46/65 patients (70.8%), respectively (p = 0.54); mean ± standard deviation of the TSH levels was 123.8 ± 46.4 µIU/mL and 274.5 ± 97.7 µIU/mL, respectively (p < 0.01), and eGFR (treatment/pre-treatment) was 0.81 and 0.99, respectively (p < 0.01). In the intermediate- and high-risk groups, the initial RAI adjuvant therapy goal was achieved in 43/63 patients (68.3%) and 33/49 (67.3%), respectively (p = 1.0). CONCLUSION: No significant differences were observed between the preparation methods in the initial achievement of RAI adjuvant therapy. However, patients in the rhTSH group demonstrated higher TSH levels and retained eGFR.

Resultados a corto plazo del tratamiento con 131I en el bocio multinodular: valor adicional de la estimulación previa con rhTSH / Short-term results of treatment with 131I in multinodular goiter: additional value of previus stimulation with Recombinant human thyrotropin

OBJETIVO: El yodo radiactivo (131I) es una opción terapeútica segura y eficaz cuando se utiliza solo o con la estimulación previa de TSH recombinante humana (rhTSH) en el tratamiento del bocio multinodular (BMN). En espera de ensayos clínicos que determinen la dosis óptima, demuestren seguridad y confirmen la eficacia, diferentes protocolos se utilizan para aplicar la dosis de 131I. Analizamos la respuesta al tratamiento con una dosis calculada por protocolo mixto (dosis fijas y cálculo por porcentaje de captación) en pacientes con BMN toxico y no toxico en nuestro hospital, en el periodo 2010-2013. MATERIALES Y MÉTODOS: Estudio prospectivo en pacientes con BMN no quirúrgico (BMNNQ) que requerían reducción del volumen glandular y/o tratamiento del hipertiroidismo. Se evaluaron 134 pacientes, 14 cumplieron con los criterios de inclusión (13mujeres) de edad media 71.08 años. Un grupo con BMN toxico, otro grupo con BMN no toxico, un tercer grupo con BMN no toxico estimulado con 0,1 mg de rhTSH previo a la dosis. Se evaluó, función tiroidea, captación tiroidea de 99ᵐTc, volumen tiroideo y síntomas compresivos. Se siguió a los pacientes durante 12 meses. RESULTADOS: Se aplicaron dosis entre 15 y 30 mCi de 131I. Remitió el hipertiroidismo en 6 de 7 pacientes. Hubo una reducción del volumen glandular (p<0.01).Los pacientes con estímulo de 0,1 mg rhTSH, aumentaron el porcentaje de captación de 99ᵐTc a las 24 h en un 32.43±10.61 permitiendo aplicar menor dosis de 131I. La tasa de aparición de hipotiroidismo fue de 7.41 por cada 100 pacientes.mes, mayor en pacientes con BMN toxico tratados con dosis bajas (p-=0.03). Hubo una mejoría subjetiva de la clínica compresiva en todos los pacientes. No hubo eventos adversos. CONCLUSIONES: Una dosis de 131I calculada por protocolo mixto es efectiva y segura para la reducción del volumen glandular y control del hipertiroidismo asociado. La estimulación con rhTSH logra el mismo efecto con una menor dosis administrada.

OBJECTIVE: Radioactive iodine (131I) is a safe and effective therapeutic option when used alone or with prior stimulation of recombinant human Thyrotropin (rhTSH) in the treatment of multinodular goiter (MNG). In absence of clinical trials that determine the optimal dose, demonstrate safety and confirm efficacy, different protocols are used to apply the dose of 131I. We analyze the response to treatment with a dose calculated by mixed protocol (fixed doses and calculation by percentage of uptake) in patients with toxic and non-toxic MNG in our hospital, in the period 2010-2013. MATERIALS AND METHODS: Prospective study in patients with non-surgical MNG that required glandular volume reduction and / or treatment of hyperthyroidism. 134 patients were evaluated, 14 met the inclusion criteria (13 women) of average age 71.08 years. One group with toxic MNG, another group with non-toxic MNG and a third with non-toxic multinodular goiter stimulated with 0.1 mg of rhTSH prior to the dose. Patients were followed for 12 months. Upon following, we assessed Thyroid function, 99ᵐTc thyroid uptake, thyroid volume and compressive symptoms. RESULTS: Doses between 15 and 30 mCi of 131I were applied. We observed hyperthyroidism remission in 6 of 7 patients. There was a reduction in glandular volume (p <0.01) considering all patients. Patients with a stimulus of 0.1 mg rhTSH, increased the percentage of uptake of 99ᵐTc at 24 h by 32.43 ± 10.61, allowing a lower dose of 131I to be applied. The rate of onset of hypothyroidism was 7.41 per 100 patients-month, and was higher in patients with toxic MNG treated with low doses (p = 0.03). There was a subjective improvement of the compression clinic in all patients. No adverse events were observed. CONCLUSIONS: A dose of 131I calculated by a mixed protocol is effective and safe for achieving glandular volume reduction and associated hyperthyroidism control. Stimulation with rhTSH produces the same effect with a lower administered dose.

Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial.

BACKGROUND: Two large randomised trials of patients with well-differentiated thyroid cancer reported in 2012 (HiLo and ESTIMABL1) found similar post-ablation success rates at 6-9 months between a low administered radioactive iodine (131I) dose (1·1 GBq) and the standard high dose (3·7 GBq). However, recurrence rates following radioactive iodine ablation have previously only been reported in observational studies, and recently in ESTIMABL1. We aimed to compare recurrence rates between radioactive iodine doses in HiLo. METHODS: HiLo was a non-inferiority, parallel, open-label, randomised controlled factorial trial done at 29 centres in the UK. Eligible patients were aged 16-80 years with histological confirmation of differentiated thyroid cancer requiring radioactive iodine ablation (performance status 0-2, tumour stage T1-T3 with the possibility of lymph-node involvement but no distant metastasis and no microscopic residual disease, and one-stage or two-stage total thyroidectomy). Patients were randomly assigned (1:1:1:1) to 1·1 GBq or 3·7 GBq ablation, each prepared with either recombinant human thyroid-stimulating hormone (rhTSH) or thyroid hormone withdrawal. Patients were followed up at annual clinic visits. Recurrences were diagnosed at each hospital with a combination of established methods according to national standards. We used Kaplan-Meier curves and hazard ratios (HRs) for time to first recurrence, which was a pre-planned secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT00415233. RESULTS: Between Jan 16, 2007, and July 1, 2010, 438 patients were randomly assigned. At the end of the follow-up period in Dec 31, 2017, median follow-up was 6·5 years (IQR 4·5-7·6) in 434 patients (217 in the low-dose group and 217 in the high-dose group). Confirmed recurrences were seen in 21 patients: 11 who had 1·1 GBq ablation and ten who had 3·7 GBq ablation. Four of these (two in each group) were considered to be persistent disease. Cumulative recurrence rates were similar between low-dose and high-dose radioactive iodine groups (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 5·9% vs 7·3%; HR 1·10 [95% CI 0·47-2·59]; p=0·83). No material difference in risk was seen for T3 or N1 disease. Recurrence rates were also similar among patients who were prepared for ablation with rhTSH and those prepared with thyroid hormone withdrawal (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 8·3% vs 5·0%; HR 1·62 [95% CI 0·67-3·91]; p=0·28). Data on adverse events were not collected during follow-up. INTERPRETATION: The recurrence rate among patients who had 1·1 GBq radioactive iodine ablation was not higher than that for 3·7 GBq, consistent with data from large, recent observational studies. These findings provide further evidence in favour of using low-dose radioactive iodine for treatment of patients with low-risk differentiated thyroid cancer. Our data also indicate that recurrence risk was not affected by use of rhTSH. FUNDING: Cancer Research UK.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b)

ABSTRACT Objective To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). Subjects and methods The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). Results One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. Conclusion Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b).

OBJECTIVE: To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). SUBJECTS AND METHODS: The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). RESULTS: One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. CONCLUSION: Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Is 131I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

OBJECTIVE: This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. SUBJECTS AND METHODS: The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). RESULTS: The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. CONCLUSIONS: Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

Is 131I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

ABSTRACT Objective This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. Subjects and methods The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

Day 3 thyroglobulin ≤ 1 ng/ml after recombinant human TSH just prior to radioactive iodine is predictive of low risk for persistent/recurrent disease in patients with papillary thyroid carcinoma.

We evaluated the negative predictive value (NPV) of thyroglobulin obtained 24 h after the second recombinant human TSH (rhTSH) ampoule (Tg-D3), before ablation with (131)I, for persistent/recurrent disease (PRD) in low/intermediate risk patients with papillary thyroid carcinoma. One hundred and one patients with Tg-D3 ≤ 1 ng/ml without anti-Tg antibodies (TgAb) were selected. Post-therapy whole-body scanning was negative for metastases in 98 (97 %) patients, and three patients showed discrete ectopic cervical uptake, but no corresponding disease was detected by neck ultrasound or computed tomography. One year after ablation, 98 (97 %) patients were free of the disease. Three patients had stimulated Tg >1 ng/ml, but no metastases were detected by the imaging methods. During follow-up (median 50 months), tumor recurrence was observed in only one patient. Thus, the NPV of Tg-D3 ≤ 1 ng/ml for PRD was 99 %. Among the 101 patients with Tg-D3 ≤ 1 ng/ml, Tg obtained 48 h after ablation (Tg-D5) continued to be ≤ 1 ng/ml in 56, and 45 had Tg-D5 >1 ng/ml. None of these 45 patients had PRD. In conclusion, Tg-D3 ≤ 1 ng/ml had a high NPV for PRD in patients without TgAb or known persistent disease and who are not at high risk. In these patients, Tg-D5 >1 ng/ml is more likely to reflect actinic damage to the remnant thyroid tissue rather than persistence of significant normal or tumor tissue.

Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the impact of treatment preparation modalities and tumor burden.

OBJECTIVE: In patients with differentiated thyroid cancer (DTC), the stimulated serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive factor of persistent disease. This prognostic value is based on data obtained after thyroid hormone withdrawal (THW), but little is known about this prognostic value after recombinant human TSH (rhTSH) stimulation and about the relationship between the stimulated Tg level and the burden of persistent tumor. We aimed to assess the impact of both radioiodine preparation modalities and persistent tumor burden on stimulated Tg levels. DESIGN AND METHODS: The stimulated Tg level was measured at radioablation in 308 consecutive DTC patients without serum Tg antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post-ablation scintigraphy included total-body scan and neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT). During a mean follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56 patients (18%). PRD was considered structural in the presence of lesions >1 cm and nonstructural otherwise. RESULTS: Nonstructural PRD was more frequent in the rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01) and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0 ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients. CONCLUSION: Both radioiodine preparation modalities and the burden of persistent tumor affect the stimulated Tg level at ablation.

Recombinant human thyroid-stimulating hormone in radioiodine thyroid remnant ablation.

BACKGROUND: To prevent the unwarranted effects of post-thyroidectomy hypothyroidism prior to radiodine (RAI) ablation, patients with well-differentiated thyroid cancer can currently undergo this treatment while in a euthyroid state. This is achieved with the use of recombinant human thyroid-stimulating hormone (rhTSH) injections prior to the ablation. OBJECTIVES: To demonstrate the efficacy of rhTSH in radioiodine thyroid ablation in patients with differentiated thyroid cancer. METHODS: We conducted a retrospective study of patients who underwent total thyroidectomy for well-differentiated thyroid cancer with different levels of risk, treated with rhTSH prior to remnant ablation with radioiodine. RESULTS: Seventeen patients with thyroid cancer were studied and followed fora median of 25 months (range 8-49 months). Ablation (defined as stimulated thyroglobulin < 1 mg/ml and negative neck ultrasonography) was successful in 15 patients (88.2%). One of the patients was lost to follow-up. CONCLUSIONS: The use of rhTSH with postoperative radioiodine ablation may be an efficient tool for sufficient thyroid remnant ablation, avoiding hypothyroidal state in the management of thyroid cancer patients.

High-risk patients with differentiated thyroid cancer T4 primary tumors achieve remnant ablation equally well using rhTSH or thyroid hormone withdrawal.

BACKGROUND: Few data exist on using thyrotropin alfa (recombinant human thyroid-stimulating hormone [rhTSH]) with radioiodine for thyroid remnant ablation of patients who have T4 primary tumors (invasion beyond the thyroid capsule). METHODS: A retrospective chart review protocol at nine centers in Europe was set up with special waiver of need for informed consent, along with a careful procedure to avoid selection bias when enrolling patients into the database. Data on 144 eligible patients with T4 tumors were collected (T4, N0-1, M0-1; mean age 49.7 years; 65% female; 88% papillary cancer). All had received (131)I remnant ablation following TSH stimulation with rhTSH or thyroid hormone withdrawal (THW) since January 2000 (rhTSH n=74, THW n=70). The primary endpoint was based on evaluation of diagnostic radioiodine scan thyroid bed uptake more than six months after the ablation procedure, while stimulated serum Tg was a secondary endpoint. Safety was evaluated within 30 days after rhTSH or (131)I. RESULTS: Successful ablation judged by scan was achieved in 65/70 (92.9%) of rhTSH and in 61/67 (91.0%) of THW patients; the success rates were comparable, since noninferiority criteria were met. Although some patients in the initial cohort had tumor in cervical nodes and metastases, considering all evaluable patients regardless of various serum anti-Tg antibody assessments, the stimulated Tg was <2 ng/mL in 48/70 (68.6%) and 39/67 (58.2%) in rhTSH and THW groups respectively; if patients with anti-Tg antibody levels >30 IU/mL were excluded, the stimulated Tg was <2 ng/mL in 42/62 (67.7%) and 37/64 (57.8%) respectively. No serious adverse events occurred within the 30-day window after ablation. CONCLUSIONS: Use of rhTSH as preparation for thyroid remnant ablation in patients with T4 primary tumors achieved a rate of ablation success that was high and noninferior to the rate seen after THW, and rhTSH was well tolerated.

[Current trends in treatment and follow-up of patients with differentiated thyroid carcinoma - experience with the use of recombinant human thyrotropin]. / Soucasné trendy v lécbe a dispenzarizaci pacientu s diferencovaným karcinomem stítné zlázy - zkusenosti s vyuzitím rekombinantního humánního tyreotropinu.

Differentiated thyroid carcinoma is the most common endocrine malignancy with an excellent prognosis in the case of its early detection. Radioiodine 131I and thyroid hormones continue to be the pivotal drugs in treatment and follow-up for more than 50 years. The therapeutical and diagnostic options were recently expanded by the use of recombinant human thyrotropin (rhTSH). Our experience with the diagnostic administration of rhTSH confirms the outcomes of official trials and also indicates that the effect of rational therapy with 131I after rhTSH is similar to the outcome after standard regime using long-term thyroid hormone withdrawal.