The Effect of Thyroid Hormone Withdrawal, Performed to Evaluate the Success of I-131 Ablation on Quality of Life and Psychological Symptoms in Female Patients With Low-risk Differentiated Thyroid Cancer

Purpose: There is a need to evaluate the treatment response in patients who have undergone radioiodine treatment (RIT) for differentiated thyroid cancer. Our study aimed to show thyroid hormone withdrawal (THW) effects on quality of life and psychological symptoms in female patients with low-risk, well-differentiated papillary thyroid cancer. Methods: We applied the short form-36 (SF-36) and Symptom Checklist-90-R (SCL-90-R) questionnaires to the patients in the euthyroid state who have referred a median of 9 months (6-13 months) after RIT to perform a diagnostic whole-body scan (dWBS) and to evaluate stimulated Tg. We applied the same questionnaire again when thyroid-stimulating hormone (TSH) was > 30 μIU/mL 4 weeks after THW (hypothyroid state). We evaluated the changes in questionnaire scores using the paired-samples t-test or the Wilcoxon signed-rank test. Results: Our study included 52 patients (median age 48 years, range 23-65 years). There was a statistically significant worsening in anxiety, psychosis, additional items, and general symptom index symptoms with the SCL-90-R questionnaire, physical functioning, role limitation due to physical health, energy/fatigue, emotional well-being, social function, general health, and health change with the SF-36 questionnaire. Conclusions: THW worsened the patients' psychological symptoms and quality of life. Thyrotropin alfa is an alternative to reduce side effects, but it can be costly and difficult to obtain in developing countries. In order to reduce the side effects of hypothyroidism and avoid the high cost, treatment response assessment can be done only in selected patient groups.

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.

Effect of TSH stimulation protocols on adequacy of low-iodine diet for radioiodine administration

Low-iodine diet (LID) is a crucial preparation for radioactive iodine (RAI) treatment or scan in thyroid cancer. The aim of this study is to analyze the influence of thyroid stimulating hormone (TSH) stimulation protocols and other clinical factors on LID adequacy. Thyroid cancer patients who underwent LID for RAI scan or treatment were retrospectively analyzed. Patients were guided to have LID for 2 weeks before RAI administration and urine iodine/creatinine ratio (UICR, μg/g Cr) was measured. TSH stimulation was conducted using either thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) injection. Adequacy of LID was classified by UICR as ‘excellent (< 50)’, ‘adequate (50–100)’, ‘inadequate (101–250)’ and ‘poor (> 250)’. A total of 1715 UICR measurements from 1054 patients were analyzed. UICR was significantly higher in case of rhTSH use than THW (72.4 ± 48.1 vs. 29.9 ± 45.8 μg/g Cr, P < 0.001). In patients who underwent LID twice using both TSH stimulation protocols alternately, UICR was higher in case of rhTSH than THW regardless of the order of method. Among clinical factors, female, old-age, and the first LID were significant factors to show higher UICR. Although the adequacy of LID was ‘adequate’ or ‘excellent’ in most patients, multivariate analysis demonstrated that THW method, male, young age, and prior LID-experience were significant determinants for achieving ‘excellent’ adequacy of LID. In conclusion, UICR was higher and the proportion of ‘excellent’ LID adequacy was lower with rhTSH than with THW. UICR was higher also in women, old-age, and LID-naïve patients. Further researches are required to suggest effective methods to reduce body iodine pool in case of rhTSH use and to validate the efficacy of such methods on outcomes of RAI treatment.

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

Objective In 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. Methods Six 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. Results In 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. Conclusions Tg1 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.

The Effect of Thyroid Hormone Withdrawal, Performed to Evaluate the Success of I-131 Ablation, On Quality of Life in Female Patients With Low-Risk Differentiated Thyroid Cancer

Objective: There is a need to evaluate the treatment response in patients who have undergone radioiodine treatment (RIT) for differentiated thyroid cancerDiagnostic tests that are used for this purpose include radioiodine whole body scan (sWBS) and serum thyroglobulin (Tg) measurement which are most accurate during thyroid-stimulating hormone (TSH) stimulation. However temporary discontinuation of thyroid hormone therapy to increase TSH (withdrawal) may be associated with the morbidity of hypothyroidism The aim of our study was to show the effects of thyroid hormone withdrawal (THW), on quality of life and psychological symptoms in female patients with low-risk, well-differentiated papillary thyroid cancer. Methods: We applied the short form-36 (SF-36) and Symptom Checklist-90-R (SCL-90-R) questionnaires to the patients in the euthyroid state who were referred a median of 9 months (6-13 months) after RIT, to perform a dWBS and to evaluate stimulated Tg. We applied the same questionnaire again when thyroid-stimulating hormone (TSH) was > 30 μIU/mL 4 weeks after THW (hypothyroid state). We evaluated the changes in questionnaire scores using the paired-samples t test or the Wilcoxon signed rank test. Results: Our study included 52 patients (median age 48 years, range 23-65 years) with differentiated cancer. Forthy –two (%) of these patients received 3700 MBq I-131 wheras 7 (%) patients received 1850 MBq. . Ablation success based on the dWBS only was 96.2%, based on Tg only was 98% and based on thyroglobulin antibodies (TgAb) only was 88.5%. There was statistically significant worsening in anxiety, psychosis, additional items and general symptom index symptoms with the SCL-90-R questionnaire, and physical functioning, role limitation due to physical health, energy/fatigue, emotional well-being, social function, general health and health change with the SF-36 questionnaire. Conclusions: THW worsened the patients’ psychological symptoms and quality of life. Our findings show that stimulated Tg and the dWBS may have side effects that outweigh benefits in patients with low-risk differentiated thyroid cancer without TgAb interference and access to ultrasonography.

The Influences of TSH Stimulation Level, Stimulated Tg Level and Tg/TSH Ratio on the Therapeutic Effect of 131I Treatment in DTC Patients

PurposeTo study the influences of pre-ablation TSH stimulation level, sTg and sTg/TSH ratio on the therapeutic effect of the first 131I treatment in DTCs.MethodsAccording to the thyroid stimulating hormone (TSH) levels (mU/l), all the 479 differentiated thyroid cancer (DTC) patients were divided into two groups: TSH &lt; 30 and TSH ≥ 30. The TSH ≥ 30 group was divided into three subgroups: 30 ≤ TSH &lt; 60, 60 ≤ TSH &lt; 90 and TSH ≥ 90. The clinical features and the therapeutic effects of the first 131I treatment were analyzed. The cutoffs of stimulated thyroglobulin (sTg) and sTg/TSH ratio were calculated to predict the therapeutic effect of 131I treatment.ResultsAmong the three subgroups, the TSH ≥ 90 subgroup was younger and less likely to be associated with cervical lymph node metastasis (LNM). The postoperative levothyroxine (L-T4) dose in the 60 ≤ TSH &lt; 90 subgroup was the lowest. Between the two groups, patients in the TSH &lt; 30 group had higher postoperative L-T4 dose and longer thyroid hormone withdrawal (THW) time. The excellent response rates six months after the first 131I treatment among the three subgroups and between the two groups were not of statistical significance. The distribution of different TSH stimulation levels among each response group was similar. The cutoffs for the better therapeutic effect of the first 131I treatment in sTg and sTg/TSH were &lt; 9.51 ng/ml and &lt; 0.11, respectively. Both univariate and multivariate logistic regressions showed that cervical LNM, distant metastasis, higher sTg and higher sTg/TSH ratio predicted poorer therapeutic effect.ConclusionsThere was no significant influence of TSH stimulation levels before the first 131I treatment on the therapeutic effect of DTC. The sTg/TSH ratio can be considered as another predictor of 131I therapeutic effect.

Effectiveness of Different Thyroid Stimulating Hormone Thresholds for Thyroid Hormone Withdrawal - Aided Radioiodine Ablation in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta - Analysis

Background: Patients with differentiated thyroid cancer (DTC) may benefit of radioiodine ablation (RAI) to reduce the probability of thyroid cancer recurrence. Guidelines recommend that thyroid stimulating hormone (TSH) of &gt;30mIU/L before RAI to optimize treatment response. However, evidence regarding this recommendation is conflicting. We conducted a systematic review and meta-analysis to compare outcomes (thyroid cancer recurrence and survival at 10 years of follow up) of stimulated TSH threshold before RAI with primary analysis focus on &lt;30 mIU/L versus ≥30 mIU/L, and subgroup analysis on &lt;90 mIU/L versus ≥90 mIU/L in patients with DTC after initial total thyroidectomy. Methods: The protocol for this study is registered and available online (CRD42020158354). Briefly, we searched several databases from their inception to April 2020. Reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each study’s risk of bias. We excluded studies that used recombinant human thyroid stimulating hormone before ablation. Results: We included five retrospective cohort studies, which enrolled a total of 2,514 patients. Risk of bias was low in four studies and high in one study. Mean age was 47 years old (ranged from 40.7 to 47.9) and most of them were female (69%). The most common DTC type was papillary thyroid cancer (78%). From those articles that reported tumor characteristics, 48% had a size ≤2cm (T1b) and 47% &gt;2cm. Moreover, 73% of the patients had no regional lymph metastasis (N0). Two studies reported radioiodine mean dose given of 30 and 100 mci. A total of 301 patients were included in the TSH threshold &lt;30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (&lt;30 mIU/L versus ≥30 mIU/L), there was difference in recurrence at 1 year (RR 2.46 (C.I. 1.09-5.55) and at 20 years (RR 1.71 (C.I. 1.19 – 2.47). However, there was no difference in mortality at 20 years (RR 0.53 (Confidence Interval (C.I.) 0.12-2.23). In addition, 10-years recurrence was not different when we compared &lt;90 mIU/L versus ≥90 mIU/L TSH (RR 1.06; 95%CI: 0.88 – 1.27). Conclusions: Mortality do not differ between recommended TSH goal (≥30 mIU/L) vs &lt;30 mIU/L in thyroid hormone withdrawal-aided radioiodine ablation in DTC patients. However, the risk of recurrence is reduced when patients achieved a TSH level &gt;30 UI/mL. These results suggest that patients may need to reach a stimulated TSH ≥30 mIU/L stimulated TSH threshold to be treated. Randomized trials are needed to confirm these findings.