rhTSH Stimulation Research Articles

TSH Stimulation before PET/CT as Our Frenemy in Detecting Thyroid Cancer Metastases-Final Results of a Retrospective Analysis.

Introduction: Non-iodine avid metastases of differentiated thyroid cancer (DTC) can be found using PET/CT with a fluorine-18-labeled glucose analog ([18F]FDG). There are ongoing discussions on the appropriateness of using exogenous thyrotropin (TSH) stimulation before this examination. Material and Methods: In a retrospective study, 73 PET/CT scans with [18F]FDG performed after exogenous stimulation with recombinant human TSH (rhTSH) and without such stimulation were analyzed. All analyzed patients were suspected of having non-iodine-avid foci of DTC. Results: The stimulation with rhTSH before the PET/CT did not affect the percentage of positive results: 37.5% (18/48) with rhTSH and 40% (10/25) without rhTSH (p = 0.83). The analysis of the ROC curves established the cut-off thyroglobulin point for a positive PET/CT result separately for both subgroups. There was no statistically significant difference between obtaining a positive PET/CT result and the baseline thyroglobulin concentration (both stimulated and unstimulated). The exogenous stimulation of TSH prior to the PET/CT had no effect on the [18F]FDG uptake in the PET/CT lesions. Conclusions: PET/CT with [18F]FDG remains a useful method for the diagnosis of non-iodine-avid DTC lesions; in the presented group, a positive effect of rhTSH stimulation on the number of DTC foci visible in the PET/CT was found, but without affecting its effectiveness.

Life-threatening amiodarone-induced thyrotoxicosis – Personalized approach to radical treatment

ObjectiveAmiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. MethodsRetrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. ResultsAn electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001–0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8–49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627–860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. ConclusionThe decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.

Increased Pituitary Fluorine-18-Fluorodeoxyglucose Uptake in Patients with Differentiated Thyroid Cancer in Hypothyroidism versus under Recombinant Human Thyroid-Stimulating Hormone Stimulation.

18F-FDG PET/CT is performed for the assessment of radioactive iodine non-avid disease in patients with DTC. In patients prepared by THW, increased pituitary uptake of 18F-FDG in the absence of pituitary disease may reflect the physiological activation of pituitary thyrotroph cells by hypothyroidism. This study aimed to compare pituitary 18F-FDG uptake in patients with DTC under THW vs. rhTSH stimulation. A total of 57 patients with DTC undergoing 18F-FDG PET/CT (40 under THW and 17 under rhTSH stimulation) were retrospectively analyzed. Pituitary metabolism was expressed as maximum standardized uptake value (SUVmax) and as SUVratio using the right cerebellum as reference. Pituitary hypermetabolism (SUVmax ≥ 4.1) was present in more patients in the THW group compared to the rhTSH group (62.5% vs. 23.5%; p = 0.01). Pituitary metabolism was significantly higher in the THW group compared to the rhTSH group, as assessed by either SUVmax (mean ± SD: 4.61 ± 1.22, 95%CI: 4.22-5.00 vs. 3.34 ± 0.86, 95%CI: 2.9-3.8; p < 0.001) or SUVratio (0.52 ± 0.11, 95%CI: 0.49-0.56 vs. 0.42 ± 0.07, 95%CI: 0.38-0.46; p < 0.001). Serum TSH levels correlated positively with SUVmax (r = 0.41, p < 0.01) and SUVratio (r = 0.44, p < 0.01) in the THW group only. The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation.

Normal organ dosimetry for thyroid cancer patients treated with radioiodine as part of the multi-centre multi-national Horizon 2020 MEDIRAD project

PurposeDosimetry is rarely performed for the treatment of differentiated thyroid cancer patients with Na[131I]I (radioiodine), and information regarding absorbed doses delivered is limited. Collection of dosimetry data in a multi-centre setting requires standardised quantitative imaging and dosimetry. A multi-national, multi-centre clinical study was performed to assess absorbed doses delivered to normal organs for differentiated thyroid cancer patients treated with Na[131I]I.MethodsPatients were enrolled in four centres and administered fixed activities of 1.1 or 3.7 GBq of Na[131I]I using rhTSH stimulation or under thyroid hormone withdrawal according to local protocols. Patients were imaged using SPECT(/CT) at variable imaging time-points following standardised acquisition and reconstruction protocols. Whole-body retention data were collected. Dosimetry for normal organs was performed at two dosimetry centres and results collated.ResultsOne hundred and five patients were recruited. Median absorbed doses per unit administered activity of 0.44, 0.14, 0.05 and 0.16 mGy/MBq were determined for the salivary glands of patients treated at centre 1, 2, 3 and 4, respectively. Median whole-body absorbed doses for 1.1 and 3.7 GBq were 0.05 Gy and 0.16 Gy, respectively. Median whole-body absorbed doses per unit administered activity of 0.04, 0.05, 0.04 and 0.04 mGy/MBq were calculated for centre 1, 2, 3 and 4, respectively.ConclusionsA wide range of normal organ doses were observed for differentiated thyroid cancer patients treated with Na[131I]I, highlighting the necessity for individualised dosimetry. The results show that data may be collated from multiple centres if minimum standards for the acquisition and dosimetry protocols can be achieved.

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.

Feasibility of Recombinant Human TSH as a Preparation for Radioiodine Therapy in Patients with Distant Metastases from Papillary Thyroid Cancer: Comparison of Long-Term Survival Outcomes with Thyroid Hormone Withdrawal.

Background: this study was designed to compare the long-term survival outcomes of patients prepared for radioiodine (RAI) therapy using either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation, by specifically focusing on cases with distant metastases from papillary thyroid cancer (PTC). Methods: A retrospective analysis was performed on 88 patients with distant metastases from PTC. Fifty-one and thirty-seven patients were prepared for RAI treatment by either THW or rhTSH stimulation, respectively. The primary endpoints were progression-free survival (PFS) and disease-specific survival (DSS). Results: The 10-year DSS rates of patients prepared for RAI therapy using either THW or rhTSH stimulation were 62.2% and 73.3%, respectively. Using multivariate analysis, RAI-avid metastases (p = 0.025) and preparation with rhTSH (p = 0.041) were identified as independent prognostic factors for PFS. Notably, PFS in the group of patients with RAI-avid metastases and preparation with rhTSH was significantly better than that in the other groups (p = 0.025). Conclusions: Preparation for RAI therapy using rhTSH stimulation is not inferior to THW preparation in terms of long-term survival outcomes experienced by patients with PTC and distant metastasis. Patients with RAI-avid metastases and preparation with rhTSH had the most favorable PFS.

Circulating MicroRNA Profiles as Potential Biomarkers for Differentiated Thyroid Cancer Recurrence.

Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer. This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease. We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next-generation sequencing to define the miRnomes along with a comprehensive quantitative PCR (qPCR) validation using 2 different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133, and OCUT-2 in response to TSH stimulation. We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed 2 putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH. The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

Clinical Outcomes After Radioiodine Therapy, According to the Method of Preparation by Recombinant TSH vs. Endogenous Hypothyroidism, in Thyroid Cancer Patients at Intermediate-High Risk of Recurrence.

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients. Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease. Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW. Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve). Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence.

Radiation exposure to allied health personnel handling blood specimens from patients receiving radioactive iodine-131 and recombinant human TSH (thyrogen®) stimulation

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103 per year (24 per day) and 8.70 × 104 per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.

Only peak thyroglobulin concentration on day 1 and 3 of rhTSH-aided RAI adjuvant treatment has prognostic implications in differentiated thyroid cancer

ObjectiveIn patients with differentiated thyroid carcinoma (DTC), serum thyroglobulin levels measured at the time of remnant ablation after thyroid hormone withdrawal were shown to have prognostic value for disease-free status. We sought to evaluate serial thyroglobulin measurements at the time of recombinant human thyroid-stimulating hormone (rhTSH)-aided iodine 131 (131I) adjuvant treatment as prognostic markers of DTC.MethodsSix hundred-fifty patients with DTC given total/near-total thyroidectomy and adjuvant radioiodine post-rhTSH stimulation were evaluated. Thyroglobulin was measured on day 1 (Tg1; at the time of the first rhTSH injection), day 3 (Tg3; 1 day after the second, final rhTSH injection), and day 6 (Tg6; 3 days post-radioiodine administration). Treatment failure was defined as histopathologically confirmed locoregional recurrence, or radiologically-evident distant metastases (signs of disease on computer tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci of radioiodine or [18F] fluorodeoxyglucose ([18F]FDG) uptake.ResultsIn univariate analysis, Tg1 (p < 0.001) and Tg3 (p < 0.001), but not Tg6, were significantly associated with structural recurrence. In multivariate analysis of the overall cohort, only Tg3 was independently associated with structural recurrence. In multivariate analysis of the subgroup (n = 561) with anti-Tg antibodies titers below the institutional cut-off, 115 IU/mL, Tg1 was an independent prognostic marker. Tg1 and Tg3 cutoffs to best predict structural recurrence were established at 0.7 ng/mL and 1.4 ng/mL, respectively.ConclusionsTg1 and Tg3, measurements made after rhTSH stimulation but before radioiodine treatment, independently predict a low risk of treatment failure in patients with DTC. Levels measured post-radioiodine application (e.g., Tg6) are highly variable, lack prognostic value, and hence can be omitted.

Evaluation of the usefulness of positron emission tomography with [18F]fluorodeoxylglucose performed to detect non-radioiodine avid recurrence and/or metastasis of differentiated thyroid cancer - a preliminary study.

About 30% of patients with disseminated differentiated thyroid cancer (DTC) may experience a loss of iodine uptake. It is associated with higher aggressiveness of the tumour and a reduced 10-year survival rate. The diagnosis of non-radioiodine avid DTC metastases remains a diagnostic challenge. A helpful technique for this diagnosis is positron emission tomography with 2-[¹⁸F]fluoro-2-deoxy-D-glucose (PET/CT with [¹⁸F]FDG). On the other hand, there are still discussions about the clinical value of using exogenous thyroid-stimulating hormone (TSH) stimulation before PET/CT with [¹⁸F]FDG. The aim of the study was the assessment of the usefulness of PET/CT with [¹⁸F]FDG under TSH suppression and stimulation of TSH performed in the detection of non-radioiodine avid DTC metastases, as well as determination of the thyroglobulin concentration under suppression and stimulation of TSH, which influences the result of PET/CT with [¹⁸F]FDG in patients with non-radioiodine avid DTC. Retrospective analysis of 37 PET/CT with [¹⁸F]FDG performed in patients with DTC diagnosed and treated at the Department of Endocrinology and Isotope Therapy of the Military Institute of Medicine from January 2018 to July 2020. Of these, PET/CT with [¹⁸F]FDG under exogenous rhTSH stimulation was performed in 22 patients and PET/CT with [¹⁸F]FDG under TSH suppression in 15 was performed. In all analyzed patients, the result of diagnostic whole-body scintigraphy (WBS) using 80 MBq ¹³¹I under rhTSH stimulation was negative, and the concentration of thyroglobulin after stimulation (sTg) was greater than 1.0 ng/mL. In the group of patients examined under TSH suppression, non-radioiodine avid in PET/CT with [¹⁸F]FDG were found in 6 out of 15 patients (40%) and in the group of patients examined under rhTSH stimulation in 10 out of 22 patients (45%). The differences between the groups were not statistically significant. The analysis of the receiver operating characteristic (ROC) curves allowed to determine the cut-off point for the positive result of PET/CT performed under TSH suppression with sTg concentration of 11.03 ng/mL. In the group of studies performed under rhTSH stimulation, the cut-off point for sTg was 6.3 ng/mL. There was no statistically significant difference between the baseline thyroglobulin (natTg) and sTg levels and the positive PET/CT result. The administration of rhTSH before the PET/CT examination also had no statistically significant effect on the maximum standard uptake value (SUVmax) of the dominant lesion identified in the PET/CT. 1) PET/CT with [¹⁸F]FDG is a useful tool for detection of non-radioiodine avid recurrence and/or metastases of DTC. 2) The concentration of natTg and sTg is highly correlated with a positive result of PET/CT with [¹⁸F]FDG. 3) The concentration of natTg is comparable with sTg in predicting a positive result of PET/CT with [¹⁸F]FDG. 4) The cut-off point for a positive result of PET/CT for natTg was 1.36 ng/mL and for sTg was 7.05 ng/mL.

Estimabl2: Is There a Need for Radioiodine Ablation in Low Risk Differentiated Thyroid Cancer (DTC) Patients?: Results From the French Randomized Phase III Prospective Trial on 776 Patients (NCT 01837745)

Background: The benefits of post-operative radioactive iodine (RAI) administration have not been demonstrated in patients with low risk differentiated thyroid cancer (DTC). The objective of this randomized phase III trial is to assess in low risk DTC patients the non-inferiority of a follow-up strategy as compared to a systematic adjuvant post-operative RAI administration. Methods: ESTIMABL2 is a French multicentric randomized phase III trial in patients with low-risk DTC treated with total thyroidectomy with or without prophylactic neck lymph node dissection (pT1am N0 or Nx with a sum of the diameters of tumor lesions ≥ 10mm, pT1b N0 or Nx). Two to five months after surgery, in the absence of suspicious lateral neck lymph node on ultrasonography (US), patients were randomized either to the follow-up group (FU, no RAI administration) or to the ablation group and received post-operative RAI (1.1 GBq following rhTSH stimulation). Yearly controls under levothyroxine treatment consisted in thyroglobulin (Tg) and Tg antibodies (TgAb) determinations and neck-US. The primary objective was to assess at 3 years after randomization the non-inferiority of the proportion of patients without tumor-related event in the FU group as compared to the ablation group. Non-inferiority is demonstrated if the rate of patients without event at 3 years does not differ by more than ΔL=-5%. A tumor-related event was defined by the occurrence of subsequent treatment (RAI administration or surgery) for abnormal RAI uptake on the post-therapeutic WBS or by elevated Tg or TgAb levels and/or abnormal neck US during controls. Tg levels on levothyroxine treatment were considered elevated if > 2ng/mL in the FU group and > 1ng/mL in the ablation group. TgAb were considered elevated if > the upper limit range with an increase above 50% on 2 consecutive determinations performed 6 months apart. Results: 776 low-risk DTC patients were included between 2013 and 2017 in 35 French centers within the TUTHYREF network; 83% females, mean age: 52 years, papillary TC: 96%, pT1bNx: 43.6%, pT1bN0: 37.5%, pT1amNx: 12.6%, pT1amN0: 6.3%. Among the 729 patients evaluable at 3 years after randomization, tumor-related events occurred in 18/367 patients (4.9% IC95%=[2.9; 7.6]) in the FU group and in 15/362 patients (4.1% IC95%=[2.3; 6.7]) in the ablation group. Thus, 95.1% of patients in the FU group had no event at 3 years and this percentage is not inferior from the 95.9% of patients observed in the ablation group (difference = -0.8% [95% CI:-3.3%; 1.8%]. The number of subsequent surgery and/or RAI administration was 6 (1.6% IC95%=[0.6; 3.5]) in the FU group and 9 (2.5% IC95%=[1.1; 4.7]) in the ablation group. Conclusion: this phase III trial demonstrates the non-inferiority of a follow-up strategy compared to a systematic adjuvant post-operative administration of RAI (1.1GBq following rhTSH) in low risk DTC patients (PHRC 2012; NCT01837745).

Influence of Levothyroxine With Recombinant Human Thyroid-Stimulating Hormone on Urinary Iodine Excretion Before Radioactive Iodine Administration

ObjectiveStimulation with recombinant human thyroid-stimulating hormone (rhTSH) before radioactive iodine administration for patients with thyroid cancer may increase the body iodine pool in the presence of continued levothyroxine; however, the precise significance of its influence remains unclear. MethodsThis was a prospective observational study conducted between March 2017 and August 2020. We measured the 24-hour urinary iodine excretion and urinary iodine-to-creatinine ratio in patients with thyroid cancer stimulated by rhTSH or thyroid hormone withdrawal (THW) before radioactive iodine administration. Oral iodine intake was controlled by a 7-day self-managed low iodine diet, followed by a strict 3-day low iodine diet while in the hospital. ResultsOverall, 343 subjects were included (rhTSH: n = 181; THW: n = 162). The mean levothyroxine dose in the rhTSH group was 115.2 μg daily. The median 24-hour urinary iodine and urinary iodine-to-creatinine ratio in the rhTSH group (71.0 [interquartile range, 57.5-88.0] μg/day and 80.0 [59.0-97.5] μg/gCr, respectively) were significantly higher than those in the THW group (42.0 [30.0-59.0] μg/day and 39.0 [28.0-61.3] μg/gCr, respectively; both P < .001). After propensity score matching by age, sex, body weight, and renal function (rhTSH: n = 106; THW: n = 106), consistent results for both values were observed for both methods. The increase in urinary iodine with the rhTSH method was smaller than the expected value calculated from the amount of levothyroxine. ConclusionUrinary iodine excretion was significantly higher among patients with rhTSH stimulation than those with THW, indicating that the rhTSH method slightly increases the body iodine pool.

Recombinant human thyroid‐stimulating hormone versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer in children, adolescents and young adults

Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well-studied in children. We aimed to measure time to disease progression after rhTSH stimulation vs. THW in pediatric patients under the age of 21 with DTC following total thyroidectomy. Retrospective cohort study (March 2001-July 2018). Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5-14). Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence. No differences were observed in tumor characteristics and I-131 dose (median 2.3 [1.8-2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127-184] mU/L), compared to those who underwent THW (136 [94.5-197] mU/L; p = 0.20). Both groups exhibited similar time to progression (p = 0.13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = 0.14). In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Lipidomic Perturbations in Cynomolgus Monkeys are Regulated by Thyroid Stimulating Hormone.

Thyroid disease affects an estimated 200 million people worldwide, and is commonly associated with increased blood lipid levels. However, the mechanism by which thyroid-stimulating hormone (TSH) affects lipid profiles is not clear. Twenty-four cynomolgus monkeys were treated with a novel exogenous recombinant human TSH (rhTSH) (SNA001) at 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1, and reference rhTSH (Thyrogen®) at 22 μg kg−1. The primary TSH (SNA001) pharmacokinetic (PK) parameters increased in a dose-dependent manner across the dose range of 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1. Peak triiodothyronine (T3) and thyroxine (T4) levels were reached within 24 h after rhTSH administration, which was delayed by approximately 20 h. In total, 420 lipid species were detected and quantified by ultra-performance liquid chromatography high resolution spectrometry (UPLC-HR-MS)-based lipidomics. Notably, peak levels of lipid accumulation, particularly sphingomyelin (SM) and triglycerides (TG), appeared at 4 and 24 h, which was consistent with the pattern of TSH and T3/T4 levels, respectively. According to weighted correlation network analysis (WGCNA), perturbations of many lipid species were strongly correlated with TSH and T3/T4 levels. TSH and the stimulated T3/T4 levels and lipid profiles following SNA001 administration were comparable to those after administration of the reference rhTSH (Thyrogen®). The plasma lipidome and changes in lipid levels after rhTSH stimulation were associated with TSH and T3/T4 concentrations. T3/T4 and lipid profiles were delayed after TSH stimulation. Such phenomena require further exploration.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2days after RaIT (late-stimulated Tg). The early response assessment was done 12months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874)ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? \u2013 experience of the Brugmann hospital in Brussels

Background131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk.The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence.MethodsPatients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment.ResultsIn total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis.Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001).131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11–11.1 GBq [30–300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11–7.4 GBq [30–200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20).ConclusionsUsing the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

MON-LB87 Recombinant Human TSH vs Thyroid Hormone Withdrawal Preparation for Radioiodine Ablation in Pediatric Differentiated Thyroid Cancer

Introduction: Recombinant human TSH (rhTSH) is commonly used to prepare patients with differentiated thyroid cancer (DTC) for radioiodine (I-131) ablation after total thyroidectomy (TT). In adults, rhTSH is associated with equivalent oncologic efficacy and improved health-related quality of life in comparison to thyroid hormone withdrawal (THW). In this study, we aimed to measure disease-free survival after rhTSH stimulation vs. THW in pediatric patients with DTC. Methods: A prospective database was analyzed for pediatric patients under the age of 21 with DTC who underwent TT and I-131 ablation with rhTSH preparation at a single tertiary institution from 2012 through 2018. These patients were compared against historical controls prepared with THW. Tumor stage, I-131 treatment details, disease-free survival, structural recurrence, biochemical recurrence (defined as serum Tg > 2 at one year), and postoperative serum TSH, thyroglobulin (Tg) and Tg antibody levels were recorded. The log-rank test was used to compare groups, and time to recurrence was estimated by Kaplan-Meier analysis. Results: Seventeen patients who received rhTSH (mean age, 16.6±3.2 [SD] years) were compared to 28 historical controls prepared with THW. No differences were observed in RAI dose (mean 2.3±0.7 mCi/kg), tumor stage, or follow-up time (median [IQR] 2.6 [1.1-3.1] years) between groups. The THW group exhibited a nonsignificantly greater recurrence rate (14 [50%], 7 with biochemical recurrence and 7 with structural recurrence) than the rhTSH group (three [18%], 2 with biochemical recurrence and 1 with structural recurrence, p=0.2). A trend toward improved disease-free survival was identified in those treated with rhTSH compared to THW. Conclusion: In this cohort of pediatric patients with DTC, we observed a trend toward improved disease-free survival among those prepared with rhTSH compared to historical controls prepared with THW. Long-term follow up is needed to better characterize outcomes associated with rhTSH stimulation prior to I-131 ablation in the pediatric population.

Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results.

Thyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay. We retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays. rhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2ng/mL. Patients with DTC with b-Tg concentrations equal or higher than 0.2ng/mL can benefit from the rhTSH stimulation test.

Analysis of activity uptake, effective half-life and time-integrated activity for low- and high-risk papillary thyroid cancer patients treated with 1.11 GBq and 3.7 GBq of 131I-NaI respectively

PurposeTo analyse the activity uptakes, effective half-lives and time-integrated activities, of relevance for remnant dosimetry, for patients treated for papillary thyroid cancer (PTC) with a different amount of activity of 131I-NaI. MethodsFifty patients were included. Of those, 18 patients had low-risk PTC and were treated with 1.11 GBq of 131I-NaI (Group 1), and 32 patients had high-risk PTC and were treated with 3.7 GBq (Group 2). Radioiodine was administered after total thyroidectomy and rhTSH stimulation. Two SPECT/CT scans were performed for each patient to determine the remnant activities and effective half-lives. ResultsSignificantly higher values (p < 0.05) were obtained for Group 1 for the remnant activity at 7 d (medians 1.4 MBq vs 0.27 MBq), the remnant activity per administered activity at 2 d (0.35% vs 0.09%) and at 7 d (0.13% vs 0.007%), and the effective half-life (93 h vs 40 h). Likewise, the time-integrated activity coefficient was significantly higher for Group 1. The time-integrated activity did not differ significantly between the two groups (p > 0.05). ConclusionsWe found a significant difference in the remnant activity per administered activity, the rate of washout from thyroid remnants, and the time-integrated activity coefficient between low-risk PTC patients treated with 1.11 GBq and high-risk PTC patients treated with 3.7 GBq. On the contrary, there was no such difference in the time-integrated activity. If remnant masses were also not statistically different (reasonable assumption for this monocentric study) no difference in time-integrated activity would imply no difference in remnant absorbed dose, of relevance for treatment efficacy and the risks of stochastic effects.